Trial Outcomes & Findings for Triptorelin With Either Exemestane or Tamoxifen in Treating Premenopausal Women With Hormone-Responsive Breast Cancer (NCT NCT00066703)

NCT ID: NCT00066703

Last Updated: 2026-02-06

Results Overview

Estimated percentage of patients alive and disease-free at 5 years from randomization, where disease-free survival is defined as the time from randomization to the first appearance of one of the following: invasive breast cancer recurrence at local, regional, or distant site, invasive contralateral breast cancer, second (non-breast) invasive cancer, or death without cancer event; or censored at date of last follow up.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 2672 participants
• Primary outcome timeframe: 5-year estimate reported at a median follow-up of 72 months
• Results posted on: 2026-02-06

Participant Flow

2672 patients were randomized between 7Nov03 and 7Apr11 at 182 centers in 15 countries.

Participant milestones

Measure	T+OFS Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.	E+OFS Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
Overall Study STARTED	1334	1338
Overall Study COMPLETED	1034	1026
Overall Study NOT COMPLETED	300	312

Reasons for withdrawal

Measure	T+OFS Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.	E+OFS Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
Overall Study Adverse Event	83	116
Overall Study Death	3	0
Overall Study Lack of Efficacy	126	78
Overall Study Lost to Follow-up	45	43
Overall Study Withdrawal by Subject	43	75

Baseline Characteristics

Triptorelin With Either Exemestane or Tamoxifen in Treating Premenopausal Women With Hormone-Responsive Breast Cancer

Baseline characteristics by cohort

Measure	E+OFS n=1332 Participants Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.	Total n=5320 Participants Total of all reporting groups	T+OFS n=1328 Participants Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
Age, Continuous Age	43 years n=1332 Participants	43 years n=2660 Participants	44 years n=1328 Participants
Sex: Female, Male Female	1332 Participants n=1332 Participants	2660 Participants n=2660 Participants	1328 Participants n=1328 Participants
Sex: Female, Male Male	0 Participants n=1332 Participants	0 Participants n=2660 Participants	0 Participants n=1328 Participants
Lymph-node status Negative	52 percent of participants n=1332 Participants	104 percent of participants n=2660 Participants	52 percent of participants n=1328 Participants
Lymph-node status Positive	48 percent of participants n=1332 Participants	96 percent of participants n=2660 Participants	48 percent of participants n=1328 Participants
Tumor size <=2 cm	59 percent of participants n=1332 Participants	119 percent of participants n=2660 Participants	60 percent of participants n=1328 Participants
Tumor size >=2 cm	40 percent of participants n=1332 Participants	79 percent of participants n=2660 Participants	39 percent of participants n=1328 Participants
Tumor size unknown	1 percent of participants n=1332 Participants	2 percent of participants n=2660 Participants	1 percent of participants n=1328 Participants
Tumor grade 1	17 percent of participants n=1332 Participants	34 percent of participants n=2660 Participants	17 percent of participants n=1328 Participants
Tumor grade 2	55 percent of participants n=1332 Participants	111 percent of participants n=2660 Participants	56 percent of participants n=1328 Participants
Tumor grade 3	27 percent of participants n=1332 Participants	53 percent of participants n=2660 Participants	26 percent of participants n=1328 Participants
Tumor grade unknown	1 percent of participants n=1332 Participants	2 percent of participants n=2660 Participants	1 percent of participants n=1328 Participants
HER2 status Negative	87 percent of participants n=1332 Participants	174 percent of participants n=2660 Participants	87 percent of participants n=1328 Participants
HER2 status Positive	12 percent of participants n=1332 Participants	24 percent of participants n=2660 Participants	12 percent of participants n=1328 Participants
HER2 status Unknown	1 percent of participants n=1332 Participants	2 percent of participants n=2660 Participants	1 percent of participants n=1328 Participants

PRIMARY outcome

Timeframe: 5-year estimate reported at a median follow-up of 72 months

Population: Intention-to-treat

Estimated percentage of patients alive and disease-free at 5 years from randomization, where disease-free survival is defined as the time from randomization to the first appearance of one of the following: invasive breast cancer recurrence at local, regional, or distant site, invasive contralateral breast cancer, second (non-breast) invasive cancer, or death without cancer event; or censored at date of last follow up.

Outcome measures

Measure	T+OFS n=1328 Participants Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.	E+OFS n=1332 Participants Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
Disease-free Survival	87.3 percentage of participants Interval 85.7 to 88.7	91.1 percentage of participants Interval 89.7 to 92.3

SECONDARY outcome

Timeframe: 5-year estimate reported at a median follow-up of 72 months

Population: Intention-to-treat

Estimated percentage of patients alive and disease-free at 5 years from randomization, where breast cancer-free interval is defined as the time from randomization to the invasive breast cancer recurrence at local, regional, or distant site, or invasive contralateral breast cancer; or censored at date of last follow up.

Outcome measures

Measure	T+OFS n=1328 Participants Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.	E+OFS n=1332 Participants Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
Breast Cancer-free Interval	88.8 percentage of participants Interval 87.3 to 90.1	92.8 percentage of participants Interval 91.6 to 93.9

SECONDARY outcome

Timeframe: 5-year estimates reported at a median follow-up of 72 months

Population: Intention-to-treat

Estimated percentage of patients alive and disease-free at 5 years from randomization, where distant recurrence-free interval is defined as the time from randomization to breast cancer recurrence at a distant site; or censored at date of last follow-up

Outcome measures

Measure	T+OFS n=1328 Participants Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.	E+OFS n=1332 Participants Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
Distant Recurrence-free Interval	92.0 percentage of participants Interval 90.7 to 93.1	93.8 percentage of participants Interval 92.7 to 94.8

SECONDARY outcome

Timeframe: 8-year estimates, reported at a median follow-up of 9 years

Population: Intention-to-treat

Estimated percentage of patients alive at 8 years from randomization, where overall survival is defined as the time from randomization to death from any cause; or censored at date last known alive.

Outcome measures

Measure	T+OFS n=1328 Participants Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.	E+OFS n=1332 Participants Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
Overall Survival	93.3 percentage of participants Interval 92.1 to 94.3	93.4 percentage of participants Interval 92.2 to 94.4

Adverse Events

T+OFS

Serious events: 484 serious events

Other events: 1293 other events

Deaths: 0 deaths

E+OFS

Serious events: 496 serious events

Other events: 1298 other events

Deaths: 0 deaths

Serious adverse events

Measure	T+OFS n=1321 participants at risk Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.	E+OFS n=1317 participants at risk Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
Blood and lymphatic system disorders Hemolysis (e.g., immune hemolytic anemia, drug related hemolysis, other)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Blood and lymphatic system disorders Thrombotic microangiopathy (e.g., thrombotic thrombocytopenic purpura or hemolytic uremic syndrome)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Blood and lymphatic system disorders Blood/Bone Marrow-Other (Specify)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Blood and lymphatic system disorders Febrile neutropenia	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Blood and lymphatic system disorders Hemoglobin	0.23% 3/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Cardiac disorders Cardiac Arrhythmia-Other (Specify)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Cardiac disorders Cardiac-ischemia/infarction	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.30% 4/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Cardiac disorders Left ventricular diastolic dysfunction	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Cardiac disorders Left ventricular systolic dysfunction	0.23% 3/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Cardiac disorders Pain - Cardiac/heart	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Cardiac disorders Supraventricular and nodal arrhythmia - Atrial fibrillation	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Cardiac disorders Supraventricular and nodal arrhythmia - Sinus tachycardia	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Cardiac disorders Supraventricular and nodal arrhythmia - Supraventricular arrhythmia NOS	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Cardiac disorders Supraventricular and nodal arrhythmia - Supraventricular tachycardia	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Cardiac disorders Valvular heart disease	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Ear and labyrinth disorders Auditory/Ear-Other (Specify)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Endocrine disorders Thyroid function, high (hyperthyroidism, thyrotoxicosis)	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Endocrine disorders Thyroid function, low (hypothyroidism)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Endocrine disorders Endocrine-Other (Specify)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Eye disorders Cataract	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Eye disorders Retinal detachment	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Eye disorders Retinopathy	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Hemorrhage, GI - Rectum	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Hemorrhage, GI - Varices (rectal)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Obstruction, GI - Small bowel NOS	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Perforation, GI - Duodenum	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Stricture/stenosis (including anastomotic), GI - Esophagus	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Ulcer, GI - Stomach	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Colitis	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Constipation	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Diarrhea	0.23% 3/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Gastritis (including bile reflux gastritis)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Gastrointestinal-Other (Specify)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.23% 3/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Hemorrhoids	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Nausea	0.68% 9/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	1.1% 15/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Pain - Abdomen NOS	0.38% 5/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.23% 3/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Pain - Stomach	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Pancreatitis	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Vomiting	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
General disorders Fatigue (asthenia, lethargy, malaise)	2.4% 32/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	3.1% 41/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
General disorders Death not associated with CTCAE term - Sudden death	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
General disorders Flu-like syndrome	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
General disorders Injection site reaction/extravasation changes	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
General disorders Pain - Chest/thorax NOS	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.30% 4/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
General disorders Pain-Other (Specify)	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Hepatobiliary disorders Obstruction, GI - Gallbladder	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Hepatobiliary disorders Cholecystitis	0.38% 5/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Hepatobiliary disorders Hepatobiliary/Pancreas-Other (Specify)	0.38% 5/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Hepatobiliary disorders Liver dysfunction/failure (clinical)	0.38% 5/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Hepatobiliary disorders Pain - Gallbladder	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	0.53% 7/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.38% 5/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Immune system disorders Allergy/Immunology-Other (Specify)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Foreign body (e.g., graft, implant)	0.30% 4/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with unknown ANC - Foreign body (e.g., graft, implant, prosthesis, stent)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection (documented clinically or microbiologically) w/Grade 3 or 4 neutrophils -Catheter-related	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Wound	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Appendix	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Bronchus	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Catheter-related	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Joint	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Kidney	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Lung (pneumonia)	0.38% 5/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Middle ear (otitis media)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Nerve-peripheral	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Pelvis NOS	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Salivary gland	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Sinus	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Skin (cellulitis)	0.61% 8/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.68% 9/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Small bowel NOS	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Soft tissue NOS	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Stomach	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Upper airway NOS	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Urinary tract NOS	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Wound	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with unknown ANC - Appendix	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with unknown ANC - Bronchus	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with unknown ANC - Lung (pneumonia)	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection with unknown ANC - Skin (cellulitis)	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.30% 4/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Infections and infestations Infection-Other (Specify)	0.30% 4/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Injury, poisoning and procedural complications Wound complication, non-infectious	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Injury, poisoning and procedural complications Fracture	0.83% 11/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	1.4% 18/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Injury, poisoning and procedural complications Intra-operative injury - Ureter	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Injury, poisoning and procedural complications Intra-operative injury - Vagina	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Injury, poisoning and procedural complications Thrombosis/embolism (vascular access-related)	2.2% 29/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.99% 13/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Injury, poisoning and procedural complications Vessel injury-vein - Extremity-upper	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Investigations ALT, SGPT (serum glutamic pyruvic transaminase)	0.45% 6/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.23% 3/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Investigations AST, SGOT (serum glutamic oxaloacetic transaminase)	0.45% 6/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.30% 4/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Investigations Cholesterol, serum-high (hypercholesterolemia)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Investigations Bilirubin (hyperbilirubinemia)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Investigations Carbon monoxide diffusion capacity (DL(co))	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Investigations GGT (gamma-glutamyl transpeptidase)	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.30% 4/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Investigations INR (International Normalized Ratio of prothrombin time)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Investigations Leukocytes (total WBC)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.23% 3/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Investigations Neutrophils/granulocytes (ANC/AGC)	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Investigations Weight loss	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	0.61% 8/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.61% 8/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Metabolism and nutrition disorders Phosphate, serum-low (hypophosphatemia)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Metabolism and nutrition disorders Triglyceride, serum-high (hypertriglyceridemia)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Metabolism and nutrition disorders Dehydration	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Metabolism and nutrition disorders Pancreatic endocrine: glucose intolerance	0.38% 5/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.61% 8/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Musculoskeletal and connective tissue disorders Extremity-upper (function)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Musculoskeletal and connective tissue disorders Joint-function	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Musculoskeletal and connective tissue disorders Lymphedema-related fibrosis	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Musculoskeletal and connective tissue disorders Musculoskeletal/Soft Tissue-Other (Specify)	0.23% 3/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Musculoskeletal and connective tissue disorders Osteoporosis	0.30% 4/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.61% 8/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Musculoskeletal and connective tissue disorders Pain - Back	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Musculoskeletal and connective tissue disorders Pain - Bone	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Musculoskeletal and connective tissue disorders Pain - Chest wall	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Musculoskeletal and connective tissue disorders Pain - Extremity-limb	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Musculoskeletal and connective tissue disorders Pain - Joint	5.2% 69/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	10.6% 139/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Musculoskeletal and connective tissue disorders Pain - Neck	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Secondary Malignancy-possibly related to cancer treatment (Specify)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders Hemorrhage, CNS	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders CNS cerebrovascular ischemia	0.68% 9/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders Dizziness	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.23% 3/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders Memory impairment	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders Neurology-Other (Specify)	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.30% 4/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders Neuropathy: cranial - CN V Motor-jaw muscles; Sensory-facial	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders Neuropathy: motor	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders Neuropathy: sensory	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders Pain - Head/headache	0.68% 9/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.84% 11/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders Pain - Neuralgia/peripheral nerve	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.91% 12/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders Seizure	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders Syncope (fainting)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.30% 4/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders Vasovagal episode	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Psychiatric disorders Insomnia	4.1% 54/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	3.3% 44/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Psychiatric disorders Mood alteration - anxiety	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.23% 3/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Psychiatric disorders Mood alteration - depression	4.5% 59/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	3.9% 51/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Psychiatric disorders Psychosis (hallucinations/delusions)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Renal and urinary disorders Incontinence, urinary	0.23% 3/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Renal and urinary disorders Obstruction, GU - Ureter	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Renal and urinary disorders Cystitis	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Renal and urinary disorders Renal/Genitourinary-Other (Specify)	1.8% 24/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.53% 7/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Reproductive system and breast disorders Hemorrhage, GU - Uterus	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Reproductive system and breast disorders Hemorrhage, GU - Vagina	0.30% 4/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Reproductive system and breast disorders Breast nipple/areolar deformity	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Reproductive system and breast disorders Irregular menses (change from baseline)	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Reproductive system and breast disorders Pain - Vagina	0.83% 11/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	2.5% 33/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Reproductive system and breast disorders Sexual/Reproductive Function-Other (Specify)	0.23% 3/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Respiratory, thoracic and mediastinal disorders Bronchospasm, wheezing	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Respiratory, thoracic and mediastinal disorders Hemorrhage, pulmonary/upper respiratory - Bronchopulmonary NOS	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Respiratory, thoracic and mediastinal disorders Apnea	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Respiratory, thoracic and mediastinal disorders Obstruction/stenosis of airway - Larynx	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory-Other (Specify)	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.15% 2/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Skin and subcutaneous tissue disorders Pruritus/itching	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Skin and subcutaneous tissue disorders Rash/desquamation	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Skin and subcutaneous tissue disorders Skin breakdown/decubitus ulcer	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Vascular disorders Hematoma	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Vascular disorders Hot flashes/flushes	11.3% 149/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	9.6% 127/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Vascular disorders Hypertension	7.6% 100/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	6.8% 90/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Vascular disorders Hypotension	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Vascular disorders Vascular-Other (Specify)	0.08% 1/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.00% 0/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Vascular disorders Vasculitis	0.00% 0/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.

Other adverse events

Measure	T+OFS n=1321 participants at risk Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.	E+OFS n=1317 participants at risk Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
Cardiac disorders Cardiac-ischemia/infarction	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.30% 4/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Gastrointestinal disorders Nausea	33.8% 446/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	36.3% 478/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
General disorders Fatigue (asthenia, lethargy, malaise)	61.1% 807/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	57.7% 760/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
General disorders Injection site reaction/extravasation changes	7.5% 99/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	6.5% 86/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	4.2% 56/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	4.6% 60/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Injury, poisoning and procedural complications Fracture	4.3% 57/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	6.2% 82/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Injury, poisoning and procedural complications Thrombosis/embolism (vascular access-related)	0.23% 3/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.23% 3/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	2.3% 30/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	2.4% 31/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Metabolism and nutrition disorders Pancreatic endocrine: glucose intolerance	1.2% 16/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	1.3% 17/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Musculoskeletal and connective tissue disorders Osteoporosis	29.4% 388/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	44.6% 588/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Musculoskeletal and connective tissue disorders Pain - Joint	72.1% 953/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	78.2% 1030/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders Hemorrhage, CNS	0.91% 12/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.53% 7/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Nervous system disorders CNS cerebrovascular ischemia	0.15% 2/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	0.08% 1/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Psychiatric disorders Insomnia	55.9% 738/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	54.2% 714/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Psychiatric disorders Libido	36.8% 486/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	42.1% 555/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Psychiatric disorders Mood alteration - depression	44.8% 592/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	46.3% 610/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Renal and urinary disorders Incontinence, urinary	17.6% 232/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	13.8% 182/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Reproductive system and breast disorders Pain - Vagina	25.4% 336/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	28.4% 374/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Reproductive system and breast disorders Vaginal dryness	46.3% 611/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	51.9% 683/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Skin and subcutaneous tissue disorders Sweating (diaphoresis)	56.9% 752/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	53.5% 705/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Vascular disorders Hot flashes/flushes	81.8% 1081/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	81.7% 1076/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.
Vascular disorders Hypertension	13.6% 179/1321 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.	16.2% 213/1317 • Assessed every 3 months for the first year, then every 6 months until year 6. Reported at a median follow-up of 72 months. Targeted adverse events and other grade 3 or higher adverse events were collected on CRFs, regardless of attribution. The safety population EXCLUDES patients who never started protocol-assigned therapy.

Additional Information

Dr. Heidi Roschitzki-Voser, PhD Head Trial Activities / Deputy Director

ETOP IBCSG Partners Foundation

Phone: 41 31 511 94 00

Email: Heidi.Roschitzki@etop.ibcsg.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place