Trial Outcomes & Findings for Maintenance Chemotherapy With or Without Local Consolidative Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer (NCT NCT03137771)

NCT ID: NCT03137771

Last Updated: 2025-11-25

Results Overview

Progression-free survival (PFS) is estimated by the Kaplan-Meier method. Progression-free survival time is measured from randomization to the first date of local or regional disease, distant metastases, second primary tumor, death due to any cause, or last known follow-up (censored). Analysis was to occur after progression or death was reported for 138 participants.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 218 participants
• Primary outcome timeframe: From randomization to first date of local or regional disease, distant metastases, second primary tumor, death, or last follow-up, whichever comes first. Maximum follow-up time at time of analysis was 5.4 years.
• Results posted on: 2025-11-25

Participant Flow

Participant milestones

Measure	Arm 2 (LCT + systemic maintenance chemotherapy) Patients undergo local consolidative therapy (LCT) over 2-5 weeks, consisting of stereotactic body radiation therapy (SBRT)/hypofractionated radiation to the primary tumor and metastatic sites or surgery of metastatic sites. Hypofractionated radiation using intensity modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3D-CRT) can be given in place of SBRT. Within 2 weeks after completion of LCT (3 weeks if surgery occurred), patients receive chemotherapy as in Arm 1.	Arm 1 (systemic maintenance chemotherapy) Patients may receive docetaxel IV over 60 minutes on day 1, erlotinib hydrochloride by mouth daily, or gemcitabine IV over 30 minutes on days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on day 1 alone or in combination with pembrolizumab IV over 30 minutes. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	136	82
Overall Study Modified intent-to-treat (MITT) population	134	81
Overall Study COMPLETED	134	81
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Maintenance Chemotherapy With or Without Local Consolidative Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Arm 1 (Systemic Maintenance Chemotherapy) n=81 Participants Patients may receive docetaxel IV over 60 minutes on day 1, erlotinib hydrochloride by mouth daily, or gemcitabine IV over 30 minutes on days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on day 1 alone or in combination with pembrolizumab IV over 30 minutes. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm 2 (LCT + Systemic Maintenance Chemotherapy) n=134 Participants Patients undergo local consolidative therapy (LCT) over 2-5 weeks, consisting of SBRT/hypofractionated radiation to the primary tumor and metastatic sites or surgery of metastatic sites. Hypofractionated radiation using IMRT or 3DCRT can be given in place of SBRT. Within 2 weeks after completion of LCT (3 weeks if surgery occurred), patients receive chemotherapy as in Arm 1.	Total n=215 Participants Total of all reporting groups
Age, Customized ≤ 49 years	4 Participants n=45 Participants	4 Participants n=12929 Participants	8 Participants n=6349 Participants
Age, Customized 50 - 59 years	15 Participants n=45 Participants	29 Participants n=12929 Participants	44 Participants n=6349 Participants
Age, Customized 60 - 69 years	31 Participants n=45 Participants	56 Participants n=12929 Participants	87 Participants n=6349 Participants
Age, Customized ≥ 70 years	31 Participants n=45 Participants	45 Participants n=12929 Participants	76 Participants n=6349 Participants
Sex: Female, Male Female	41 Participants n=45 Participants	66 Participants n=12929 Participants	107 Participants n=6349 Participants
Sex: Female, Male Male	40 Participants n=45 Participants	68 Participants n=12929 Participants	108 Participants n=6349 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=45 Participants	7 Participants n=12929 Participants	9 Participants n=6349 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	78 Participants n=45 Participants	118 Participants n=12929 Participants	196 Participants n=6349 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=45 Participants	9 Participants n=12929 Participants	10 Participants n=6349 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=45 Participants	1 Participants n=12929 Participants	2 Participants n=6349 Participants
Race (NIH/OMB) Asian	2 Participants n=45 Participants	2 Participants n=12929 Participants	4 Participants n=6349 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=45 Participants	0 Participants n=12929 Participants	0 Participants n=6349 Participants
Race (NIH/OMB) Black or African American	16 Participants n=45 Participants	19 Participants n=12929 Participants	35 Participants n=6349 Participants
Race (NIH/OMB) White	59 Participants n=45 Participants	106 Participants n=12929 Participants	165 Participants n=6349 Participants
Race (NIH/OMB) More than one race	1 Participants n=45 Participants	0 Participants n=12929 Participants	1 Participants n=6349 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=45 Participants	6 Participants n=12929 Participants	8 Participants n=6349 Participants
Zubrod performance status 0	35 Participants n=45 Participants	47 Participants n=12929 Participants	82 Participants n=6349 Participants
Zubrod performance status 1	44 Participants n=45 Participants	79 Participants n=12929 Participants	123 Participants n=6349 Participants
Zubrod performance status 2	2 Participants n=45 Participants	8 Participants n=12929 Participants	10 Participants n=6349 Participants
Histology Non-Squamous cell carcinoma	64 Participants n=45 Participants	104 Participants n=12929 Participants	168 Participants n=6349 Participants
Histology Squamous cell carcinoma	17 Participants n=45 Participants	30 Participants n=12929 Participants	47 Participants n=6349 Participants
Systemic Therapy Type Cytotoxic Chemotherapy	14 Participants n=45 Participants	16 Participants n=12929 Participants	30 Participants n=6349 Participants
Systemic Therapy Type Immunotherapy	67 Participants n=45 Participants	118 Participants n=12929 Participants	185 Participants n=6349 Participants
Number of lesions targeted during treatment 1	50 Participants n=45 Participants	78 Participants n=12929 Participants	128 Participants n=6349 Participants
Number of lesions targeted during treatment 2	19 Participants n=45 Participants	36 Participants n=12929 Participants	55 Participants n=6349 Participants
Number of lesions targeted during treatment 3	12 Participants n=45 Participants	18 Participants n=12929 Participants	30 Participants n=6349 Participants
Number of lesions targeted during treatment 4	0 Participants n=45 Participants	1 Participants n=12929 Participants	1 Participants n=6349 Participants
Number of lesions targeted during treatment 5	0 Participants n=45 Participants	1 Participants n=12929 Participants	1 Participants n=6349 Participants

PRIMARY outcome

Timeframe: From randomization to first date of local or regional disease, distant metastases, second primary tumor, death, or last follow-up, whichever comes first. Maximum follow-up time at time of analysis was 5.4 years.

Population: Modified intent-to-treat population (randomized eligible participants).

Progression-free survival (PFS) is estimated by the Kaplan-Meier method. Progression-free survival time is measured from randomization to the first date of local or regional disease, distant metastases, second primary tumor, death due to any cause, or last known follow-up (censored). Analysis was to occur after progression or death was reported for 138 participants.

Outcome measures

Measure	Arm 1 (systemic maintenance chemotherapy) n=81 Participants Patients may receive docetaxel IV over 60 minutes on day 1, erlotinib hydrochloride by mouth daily, or gemcitabine IV over 30 minutes on days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on day 1 alone or in combination with pembrolizumab IV over 30 minutes. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm 2 (LCT + systemic maintenance chemotherapy) n=134 Participants Patients undergo local consolidative therapy (LCT) over 2-5 weeks, consisting of SBRT/hypofractionated radiation to the primary tumor and metastatic sites or surgery of metastatic sites. Hypofractionated radiation using IMRT or 3DCRT can be given in place of SBRT. Within 2 weeks after completion of LCT (3 weeks if surgery occurred), patients receive chemotherapy as in Arm 1.
[Phase II] Progression-free Survival	11.1 months Interval 6.9 to 21.4	13.7 months Interval 8.6 to 20.1

PRIMARY outcome

Timeframe: From randomization to death or last follow-up.

Population: The phase III component did not open, therefore there are no participants for this outcome measure.

Overall survival is estimated by the Kaplan-Meier method. Survival time is measured from randomization to date of death from any cause or last known follow-up (censored). Analysis was to occur after **** deaths were reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From randomization to first in-field failure, death or last follow-up, whichever occurs first. Maximum follow-up at time of analysis was 5.4 years. The one- and two-year estimates are reported.

Population: Modified intent-to-treat population (randomized eligible participants).

In-field local failure is defined as local or marginal failure. In-field local failure rates are estimated by the cumulative incidence method, in which death without failure is treated as competing risk and participants alive without failure are censored at last known follow-up. Analysis was to occur after progression or death was reported for 138 participants.

Outcome measures

Measure	Arm 1 (systemic maintenance chemotherapy) n=81 Participants Patients may receive docetaxel IV over 60 minutes on day 1, erlotinib hydrochloride by mouth daily, or gemcitabine IV over 30 minutes on days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on day 1 alone or in combination with pembrolizumab IV over 30 minutes. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm 2 (LCT + systemic maintenance chemotherapy) n=134 Participants Patients undergo local consolidative therapy (LCT) over 2-5 weeks, consisting of SBRT/hypofractionated radiation to the primary tumor and metastatic sites or surgery of metastatic sites. Hypofractionated radiation using IMRT or 3DCRT can be given in place of SBRT. Within 2 weeks after completion of LCT (3 weeks if surgery occurred), patients receive chemotherapy as in Arm 1.
In-Field Local Failure 1 year	15.3 percentage of participants Interval 8.1 to 24.6	8.6 percentage of participants Interval 4.6 to 14.3
In-Field Local Failure 2 years	19.8 percentage of participants Interval 11.4 to 29.9	13.4 percentage of participants Interval 8.1 to 20.0

SECONDARY outcome

Timeframe: From randomization to the first occurrence of any new lesions, death, or last follow-up, whichever occurs first. Maximum follow-up time at the time of analysis was 5.4 years. One- and two-year estimates are reported.

Population: Modified intent-to-treat population (randomized eligible participants).

New lesion rates are estimated by the cumulative incidence method, in which death without new lesions is treated as competing risk and participants alive without new lesions are censored at last known follow-up. Analysis was to occur after progression or death was reported for 138 participants.

Outcome measures

Measure	Arm 1 (systemic maintenance chemotherapy) n=81 Participants Patients may receive docetaxel IV over 60 minutes on day 1, erlotinib hydrochloride by mouth daily, or gemcitabine IV over 30 minutes on days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on day 1 alone or in combination with pembrolizumab IV over 30 minutes. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm 2 (LCT + systemic maintenance chemotherapy) n=134 Participants Patients undergo local consolidative therapy (LCT) over 2-5 weeks, consisting of SBRT/hypofractionated radiation to the primary tumor and metastatic sites or surgery of metastatic sites. Hypofractionated radiation using IMRT or 3DCRT can be given in place of SBRT. Within 2 weeks after completion of LCT (3 weeks if surgery occurred), patients receive chemotherapy as in Arm 1.
Development of New Lesions 1 year	32.5 percentage of participants Interval 21.8 to 43.5	28.1 percentage of participants Interval 20.6 to 36.1
Development of New Lesions 2 years	41.5 percentage of participants Interval 29.7 to 52.9	30.5 percentage of participants Interval 22.7 to 38.6

SECONDARY outcome

Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 5.4 years.

Population: Modified intent-to-treat population (randomized and eligible) who received any protocol treatment.

National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

Outcome measures

Measure	Arm 1 (systemic maintenance chemotherapy) n=73 Participants Patients may receive docetaxel IV over 60 minutes on day 1, erlotinib hydrochloride by mouth daily, or gemcitabine IV over 30 minutes on days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on day 1 alone or in combination with pembrolizumab IV over 30 minutes. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm 2 (LCT + systemic maintenance chemotherapy) n=130 Participants Patients undergo local consolidative therapy (LCT) over 2-5 weeks, consisting of SBRT/hypofractionated radiation to the primary tumor and metastatic sites or surgery of metastatic sites. Hypofractionated radiation using IMRT or 3DCRT can be given in place of SBRT. Within 2 weeks after completion of LCT (3 weeks if surgery occurred), patients receive chemotherapy as in Arm 1.
Number of Participants by Highest Grade Adverse Event Reported Grade 1	7 Participants	6 Participants
Number of Participants by Highest Grade Adverse Event Reported Grade 2	15 Participants	37 Participants
Number of Participants by Highest Grade Adverse Event Reported Grade 3	35 Participants	56 Participants
Number of Participants by Highest Grade Adverse Event Reported Grade 4	11 Participants	20 Participants
Number of Participants by Highest Grade Adverse Event Reported Grade 5	4 Participants	10 Participants
Number of Participants by Highest Grade Adverse Event Reported None	1 Participants	1 Participants

SECONDARY outcome

Timeframe: From randomization to last chemotherapy, which continues until progression or significant toxicity. Maximum follow-up at time of analysis was 5.4 years.

Population: Modified intent-to-treat population (randomized eligible participants).

Duration of Maintenance Chemotherapy

Outcome measures

Measure	Arm 1 (systemic maintenance chemotherapy) n=81 Participants Patients may receive docetaxel IV over 60 minutes on day 1, erlotinib hydrochloride by mouth daily, or gemcitabine IV over 30 minutes on days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on day 1 alone or in combination with pembrolizumab IV over 30 minutes. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm 2 (LCT + systemic maintenance chemotherapy) n=134 Participants Patients undergo local consolidative therapy (LCT) over 2-5 weeks, consisting of SBRT/hypofractionated radiation to the primary tumor and metastatic sites or surgery of metastatic sites. Hypofractionated radiation using IMRT or 3DCRT can be given in place of SBRT. Within 2 weeks after completion of LCT (3 weeks if surgery occurred), patients receive chemotherapy as in Arm 1.
Duration of Maintenance Chemotherapy	5.46 months Interval 2.07 to 17.95	6.20 months Interval 2.81 to 16.86

Adverse Events

Arm 2 (LCT + systemic maintenance chemotherapy)

Serious events: 40 serious events

Other events: 129 other events

Deaths: 70 deaths

Arm 1 (systemic maintenance chemotherapy)

Serious events: 14 serious events

Other events: 71 other events

Deaths: 37 deaths

Serious adverse events

Measure	Arm 2 (LCT + systemic maintenance chemotherapy) n=130 participants at risk Patients undergo local consolidative therapy (LCT) over 2-5 weeks, consisting of SBRT/hypofractionated radiation to the primary tumor and metastatic sites or surgery of metastatic sites. Hypofractionated radiation using IMRT or 3DCRT can be given in place of SBRT. Within 2 weeks after completion of LCT (3 weeks if surgery occurred), patients receive chemotherapy as in Arm 1.	Arm 1 (systemic maintenance chemotherapy) n=73 participants at risk Patients may receive docetaxel IV over 60 minutes on day 1, erlotinib hydrochloride by mouth daily, or gemcitabine IV over 30 minutes on days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on day 1 alone or in combination with pembrolizumab IV over 30 minutes. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	2.3% 3/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Blood and lymphatic system disorders Febrile neutropenia	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Cardiac disorders Cardiac arrest	0.00% 0/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Cardiac disorders Cardiac disorders - Other	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Cardiac disorders Chest pain - cardiac	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Cardiac disorders Myocardial infarction	2.3% 3/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Cardiac disorders Pericardial effusion	0.00% 0/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Cardiac disorders Pericarditis	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Cardiac disorders Sinus tachycardia	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Endocrine disorders Hypophysitis	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Colitis	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Colonic perforation	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Diarrhea	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Esophageal pain	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Esophagitis	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Nausea	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Death NOS	1.5% 2/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Disease progression	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Fatigue	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Malaise	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Sudden death NOS	0.00% 0/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Hepatobiliary disorders Cholecystitis	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Infections and infestations Cytomegalovirus infection reactivation	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Infections and infestations Encephalitis infection	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Infections and infestations Herpes simplex reactivation	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Infections and infestations Lung infection	4.6% 6/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Infections and infestations Sepsis	2.3% 3/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Injury, poisoning and procedural complications Fall	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Injury, poisoning and procedural complications Postoperative hemorrhage	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Alkaline phosphatase increased	0.00% 0/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Aspartate aminotransferase increased	0.00% 0/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Ejection fraction decreased	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Neutrophil count decreased	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations White blood cell decreased	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Acidosis	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Anorexia	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Dehydration	1.5% 2/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Hyperglycemia	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Hyponatremia	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Cognitive disturbance	0.00% 0/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Ischemia cerebrovascular	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Peripheral sensory neuropathy	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Seizure	0.00% 0/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	2.7% 2/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Stroke	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Psychiatric disorders Confusion	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Renal and urinary disorders Acute kidney injury	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Renal and urinary disorders Urinary incontinence	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Renal and urinary disorders Urinary tract obstruction	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	3.8% 5/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.3% 3/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.4% 7/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	2.7% 2/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.8% 5/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	0.00% 0/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Vascular disorders Arterial thromboembolism	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Vascular disorders Hypotension	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Vascular disorders Thromboembolic event	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.

Other adverse events

Measure	Arm 2 (LCT + systemic maintenance chemotherapy) n=130 participants at risk Patients undergo local consolidative therapy (LCT) over 2-5 weeks, consisting of SBRT/hypofractionated radiation to the primary tumor and metastatic sites or surgery of metastatic sites. Hypofractionated radiation using IMRT or 3DCRT can be given in place of SBRT. Within 2 weeks after completion of LCT (3 weeks if surgery occurred), patients receive chemotherapy as in Arm 1.	Arm 1 (systemic maintenance chemotherapy) n=73 participants at risk Patients may receive docetaxel IV over 60 minutes on day 1, erlotinib hydrochloride by mouth daily, or gemcitabine IV over 30 minutes on days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on day 1 alone or in combination with pembrolizumab IV over 30 minutes. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	51.5% 67/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	46.6% 34/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	3.1% 4/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Cardiac disorders Atrial fibrillation	6.2% 8/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	0.00% 0/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Cardiac disorders Cardiac disorders - Other	3.8% 5/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Cardiac disorders Sinus tachycardia	7.7% 10/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	2.7% 2/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Ear and labyrinth disorders Hearing impaired	7.7% 10/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	8.2% 6/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Endocrine disorders Hyperthyroidism	1.5% 2/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	8.2% 6/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Endocrine disorders Hypothyroidism	10.8% 14/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	20.5% 15/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Eye disorders Blurred vision	9.2% 12/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	9.6% 7/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Eye disorders Dry eye	3.8% 5/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	11.0% 8/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Eye disorders Eye disorders - Other	4.6% 6/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	13.7% 10/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Eye disorders Eye pain	1.5% 2/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Eye disorders Watering eyes	2.3% 3/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	8.2% 6/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Abdominal pain	18.5% 24/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	17.8% 13/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Constipation	26.2% 34/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	30.1% 22/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Diarrhea	25.4% 33/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	30.1% 22/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Dry mouth	4.6% 6/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	9.6% 7/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Dyspepsia	6.9% 9/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	11.0% 8/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Dysphagia	16.9% 22/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Esophagitis	16.9% 22/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Gastroesophageal reflux disease	9.2% 12/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Gastrointestinal disorders - Other	7.7% 10/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	9.6% 7/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Mucositis oral	10.0% 13/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Nausea	35.4% 46/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	42.5% 31/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Gastrointestinal disorders Vomiting	20.0% 26/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	20.5% 15/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Chills	13.1% 17/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Edema face	4.6% 6/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Edema limbs	19.2% 25/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	26.0% 19/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Fatigue	70.0% 91/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	57.5% 42/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Fever	15.4% 20/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	12.3% 9/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Gait disturbance	5.4% 7/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	11.0% 8/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions General disorders and administration site conditions - Other	8.5% 11/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	11.0% 8/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Investigations - Other	10.8% 14/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	8.2% 6/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Localized edema	9.2% 12/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Non-cardiac chest pain	15.4% 20/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	11.0% 8/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
General disorders and administration site conditions Pain	13.1% 17/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	11.0% 8/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Infections and infestations Infections and infestations - Other	13.1% 17/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	11.0% 8/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Infections and infestations Lung infection	17.7% 23/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Infections and infestations Sepsis	5.4% 7/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	4.1% 3/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Infections and infestations Skin infection	1.5% 2/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Infections and infestations Upper respiratory infection	6.2% 8/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Infections and infestations Urinary tract infection	9.2% 12/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	8.2% 6/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Injury, poisoning and procedural complications Bruising	6.9% 9/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Injury, poisoning and procedural complications Fall	8.5% 11/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	16.4% 12/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other	3.1% 4/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	9.6% 7/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Alanine aminotransferase increased	18.5% 24/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	20.5% 15/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Alkaline phosphatase increased	14.6% 19/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	12.3% 9/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Aspartate aminotransferase increased	15.4% 20/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	21.9% 16/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Blood bilirubin increased	3.1% 4/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Cholesterol high	3.8% 5/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Creatinine increased	26.2% 34/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	27.4% 20/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Lymphocyte count decreased	43.8% 57/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	21.9% 16/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Neutrophil count decreased	12.3% 16/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	9.6% 7/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Platelet count decreased	20.0% 26/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	15.1% 11/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Thyroid stimulating hormone increased	4.6% 6/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	11.0% 8/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Weight gain	5.4% 7/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations Weight loss	19.2% 25/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	17.8% 13/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Investigations White blood cell decreased	23.8% 31/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	12.3% 9/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Anorexia	29.2% 38/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	26.0% 19/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Dehydration	9.2% 12/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	2.7% 2/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Hypercalcemia	13.8% 18/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	11.0% 8/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Hyperglycemia	26.9% 35/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	35.6% 26/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Hyperkalemia	12.3% 16/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	12.3% 9/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Hypoalbuminemia	16.9% 22/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	24.7% 18/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Hypocalcemia	8.5% 11/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	12.3% 9/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Hypokalemia	25.4% 33/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	24.7% 18/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Hypomagnesemia	6.9% 9/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	4.1% 3/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Metabolism and nutrition disorders Hyponatremia	23.8% 31/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	30.1% 22/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Musculoskeletal and connective tissue disorders Arthralgia	13.1% 17/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	12.3% 9/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Musculoskeletal and connective tissue disorders Arthritis	10.8% 14/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Musculoskeletal and connective tissue disorders Back pain	24.6% 32/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	21.9% 16/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Musculoskeletal and connective tissue disorders Bone pain	4.6% 6/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Musculoskeletal and connective tissue disorders Chest wall pain	6.9% 9/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	2.7% 2/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	7.7% 10/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	13.7% 10/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Musculoskeletal and connective tissue disorders Muscle cramp	3.1% 4/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	6.2% 8/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	10.8% 14/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	11.0% 8/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Musculoskeletal and connective tissue disorders Myalgia	14.6% 19/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	20.5% 15/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Musculoskeletal and connective tissue disorders Neck pain	13.1% 17/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	8.2% 6/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	10.8% 14/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	20.5% 15/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Concentration impairment	1.5% 2/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Dizziness	24.6% 32/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	21.9% 16/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Dysesthesia	2.3% 3/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Dysgeusia	9.2% 12/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	9.6% 7/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Headache	20.8% 27/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	27.4% 20/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Memory impairment	9.2% 12/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	9.6% 7/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Paresthesia	8.5% 11/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	13.7% 10/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Peripheral motor neuropathy	2.3% 3/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	8.2% 6/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Peripheral sensory neuropathy	18.5% 24/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	17.8% 13/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Nervous system disorders Tremor	6.9% 9/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Psychiatric disorders Anxiety	10.0% 13/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	15.1% 11/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Psychiatric disorders Confusion	3.1% 4/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	13.7% 10/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Psychiatric disorders Depression	10.8% 14/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	15.1% 11/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Psychiatric disorders Insomnia	19.2% 25/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	13.7% 10/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Renal and urinary disorders Chronic kidney disease	6.2% 8/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Renal and urinary disorders Dysuria	3.1% 4/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Renal and urinary disorders Proteinuria	4.6% 6/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Renal and urinary disorders Renal and urinary disorders - Other	3.8% 5/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Renal and urinary disorders Urinary frequency	6.2% 8/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Renal and urinary disorders Urinary incontinence	3.1% 4/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Renal and urinary disorders Urinary urgency	6.2% 8/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Reproductive system and breast disorders Pelvic pain	1.5% 2/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	6.9% 9/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	13.7% 10/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Cough	37.7% 49/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	27.4% 20/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	48.5% 63/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	37.0% 27/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.2% 8/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Hoarseness	6.2% 8/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	2.7% 2/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	17.7% 23/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	8.2% 6/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Nasal congestion	14.6% 19/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	15.1% 11/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	10.8% 14/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	4.1% 3/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	18.5% 24/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	15.1% 11/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	26.9% 35/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	13.7% 10/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	7.7% 10/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Sleep apnea	0.77% 1/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Sore throat	7.7% 10/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	4.1% 3/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Respiratory, thoracic and mediastinal disorders Wheezing	11.5% 15/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	1.4% 1/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Skin and subcutaneous tissue disorders Alopecia	5.4% 7/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	8.2% 6/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Skin and subcutaneous tissue disorders Dry skin	4.6% 6/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	9.6% 7/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Skin and subcutaneous tissue disorders Hyperhidrosis	7.7% 10/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	8.2% 6/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Skin and subcutaneous tissue disorders Pruritus	16.2% 21/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	13.7% 10/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	10.0% 13/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	12.3% 9/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	14.6% 19/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	16.4% 12/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Vascular disorders Hot flashes	3.8% 5/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	6.8% 5/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Vascular disorders Hypertension	23.8% 31/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	32.9% 24/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.
Vascular disorders Hypotension	13.1% 17/130 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.	5.5% 4/73 • From baseline to date of last known follow-up. Maximum follow-up time was 5.4 years. All-cause mortality was assessed in the modified intent-to-treat population (MITT) (randomized and eligible). Adverse events were assessed in the MITT population that started protocol treatment.

Additional Information

Wendy Seiferheld

NRG Oncology

Phone: 2155743208

Email: seiferheldw@nrgoncology.org

Results disclosure agreements

• Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
• Publication restrictions are in place

Restriction type: OTHER