Trial Outcomes & Findings for Pembrolizumab and Doxorubicin Hydrochloride or Anti-Estrogen Therapy in Treating Patients With Triple-Negative or Hormone Receptor-Positive Metastatic Breast Cancer (NCT NCT02648477)

NCT ID: NCT02648477

Last Updated: 2024-03-19

Results Overview

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: Up to 3 years
• Results posted on: 2024-03-19

Participant Flow

Participant milestones

Measure	Cohort 1 (Pembrolizumab, Doxorubicin Hydrochloride) Triple Negative Breast Cancer Pembrolizumab 200 mg IV every 3 weeks and doxorubicin 50-60 mg/m2 IV every 3 weeks x 6 cycles followed by a pembrolizumab alone for up to 35 cycles or a maximum of 24 months starting from the first cycle. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Doxorubicin Hydrochloride: Given IV Pembrolizumab: Given IV	Cohort 2 (Pembrolizumab, Anti-estrogen Therapy) HR+ HER2- Breast Cancer Pembrolizumab 200 mg IV every 3 weeks and anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg (preferred) daily. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Pembrolizumab: Given IV
Overall Study STARTED	10	20
Overall Study COMPLETED	10	20
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pembrolizumab and Doxorubicin Hydrochloride or Anti-Estrogen Therapy in Treating Patients With Triple-Negative or Hormone Receptor-Positive Metastatic Breast Cancer

Baseline characteristics by cohort

Measure	Cohort 1 (Pembrolizumab, Doxorubicin Hydrochloride) Triple Negative Breast Cancer n=10 Participants Pembrolizumab 200 mg IV every 3 weeks and doxorubicin 50-60 mg/m2 IV every 3 weeks x 6 cycles followed by a pembrolizumab alone for up to 35 cycles or a maximum of 24 months starting from the first cycle. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Doxorubicin Hydrochloride: Given IV Pembrolizumab: Given IV	Cohort 2 (Pembrolizumab, Anti-estrogen Therapy) HR+ HER2- Breast Cancer n=20 Participants Pembrolizumab 200 mg IV every 3 weeks and anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg (preferred) daily. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Pembrolizumab: Given IV	Total n=30 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	62 years n=7 Participants	62 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	20 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants	15 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	20 participants n=7 Participants	30 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 3 years

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Outcome measures

Measure	Cohort 1 (Pembrolizumab, Doxorubicin Hydrochloride) Triple Negative Breast Cancer n=10 Participants Pembrolizumab 200 mg IV every 3 weeks and doxorubicin 50-60 mg/m2 IV every 3 weeks x 6 cycles followed by a pembrolizumab alone for up to 35 cycles or a maximum of 24 months starting from the first cycle. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Doxorubicin Hydrochloride: Given IV Pembrolizumab: Given IV	Cohort 2 (Pembrolizumab, Anti-estrogen Therapy) HR+ HER2- Breast Cancer n=20 Participants Pembrolizumab 200 mg IV every 3 weeks and anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg (preferred) daily. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Pembrolizumab: Given IV
Number of Participants With Overall Response	5 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 6 months

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI:

Complete Response (CR), Disappearance of all target lesions; Partial response (PR): At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR; Stable disease (SD): Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD; Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). Clinical Benefit Rate (CBR) = CR + PR + SD at 6 months

Outcome measures

Measure	Cohort 1 (Pembrolizumab, Doxorubicin Hydrochloride) Triple Negative Breast Cancer n=10 Participants Pembrolizumab 200 mg IV every 3 weeks and doxorubicin 50-60 mg/m2 IV every 3 weeks x 6 cycles followed by a pembrolizumab alone for up to 35 cycles or a maximum of 24 months starting from the first cycle. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Doxorubicin Hydrochloride: Given IV Pembrolizumab: Given IV	Cohort 2 (Pembrolizumab, Anti-estrogen Therapy) HR+ HER2- Breast Cancer n=20 Participants Pembrolizumab 200 mg IV every 3 weeks and anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg (preferred) daily. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Pembrolizumab: Given IV
Clinical Benefit Rate	50 percentage of participants	20 percentage of participants

SECONDARY outcome

Timeframe: Up to 3 years

Estimated using the product-limit method of Kaplan and Meier. From initial treatment until death from any cause.

Outcome measures

Measure	Cohort 1 (Pembrolizumab, Doxorubicin Hydrochloride) Triple Negative Breast Cancer n=10 Participants Pembrolizumab 200 mg IV every 3 weeks and doxorubicin 50-60 mg/m2 IV every 3 weeks x 6 cycles followed by a pembrolizumab alone for up to 35 cycles or a maximum of 24 months starting from the first cycle. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Doxorubicin Hydrochloride: Given IV Pembrolizumab: Given IV	Cohort 2 (Pembrolizumab, Anti-estrogen Therapy) HR+ HER2- Breast Cancer n=20 Participants Pembrolizumab 200 mg IV every 3 weeks and anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg (preferred) daily. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Pembrolizumab: Given IV
Overall Survival (OS)	15.6 Months Interval 13.3 to NA - The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	17.2 Months Interval 9.4 to NA - The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

SECONDARY outcome

Timeframe: Up to 3 years

Estimated using the product-limit method of Kaplan and Meier. Failure defined as disease progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure	Cohort 1 (Pembrolizumab, Doxorubicin Hydrochloride) Triple Negative Breast Cancer n=10 Participants Pembrolizumab 200 mg IV every 3 weeks and doxorubicin 50-60 mg/m2 IV every 3 weeks x 6 cycles followed by a pembrolizumab alone for up to 35 cycles or a maximum of 24 months starting from the first cycle. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Doxorubicin Hydrochloride: Given IV Pembrolizumab: Given IV	Cohort 2 (Pembrolizumab, Anti-estrogen Therapy) HR+ HER2- Breast Cancer n=20 Participants Pembrolizumab 200 mg IV every 3 weeks and anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg (preferred) daily. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Pembrolizumab: Given IV
Progression-free Survival (PFS)	5.2 Months Interval 4.7 to NA - The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	1.8 Months Interval 1.6 to 2.6

Adverse Events

Cohort 1 (Pembrolizumab, Doxorubicin Hydrochloride) Triple Negative Breast Cancer

Serious events: 3 serious events

Other events: 10 other events

Deaths: 7 deaths

Cohort 2 (Pembrolizumab, Anti-estrogen Therapy) HR+ HER2- Breast Cancer

Serious events: 2 serious events

Other events: 20 other events

Deaths: 16 deaths

Serious adverse events

Measure	Cohort 1 (Pembrolizumab, Doxorubicin Hydrochloride) Triple Negative Breast Cancer n=10 participants at risk Pembrolizumab 200 mg IV every 3 weeks and doxorubicin 50-60 mg/m2 IV every 3 weeks x 6 cycles followed by a pembrolizumab alone for up to 35 cycles or a maximum of 24 months starting from the first cycle. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Doxorubicin Hydrochloride: Given IV Pembrolizumab: Given IV	Cohort 2 (Pembrolizumab, Anti-estrogen Therapy) HR+ HER2- Breast Cancer n=20 participants at risk Pembrolizumab 200 mg IV every 3 weeks and anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg (preferred) daily. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Pembrolizumab: Given IV
Cardiac disorders Heart failure	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Infusion related reaction	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Infections and infestations - Other, spe	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Neutrophil count decreased	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Acute kidney injury	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hypotension	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Other adverse events

Measure	Cohort 1 (Pembrolizumab, Doxorubicin Hydrochloride) Triple Negative Breast Cancer n=10 participants at risk Pembrolizumab 200 mg IV every 3 weeks and doxorubicin 50-60 mg/m2 IV every 3 weeks x 6 cycles followed by a pembrolizumab alone for up to 35 cycles or a maximum of 24 months starting from the first cycle. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Doxorubicin Hydrochloride: Given IV Pembrolizumab: Given IV	Cohort 2 (Pembrolizumab, Anti-estrogen Therapy) HR+ HER2- Breast Cancer n=20 participants at risk Pembrolizumab 200 mg IV every 3 weeks and anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg (preferred) daily. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. Anastrozole: Given PO Exemestane: Given PO Letrozole: Given PO Pembrolizumab: Given IV
Blood and lymphatic system disorders Anemia	80.0% 8/10 • Number of events 23 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	35.0% 7/20 • Number of events 12 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Cardiac disorders - Other, specify	20.0% 2/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Palpitations	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Sinus tachycardia	30.0% 3/10 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, spe	10.0% 1/10 • Number of events 6 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Ear and labyrinth disorders Tinnitus	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Endocrine disorders Hyperthyroidism	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Endocrine disorders Hypothyroidism	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Blurred vision	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Conjunctivitis	20.0% 2/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Dry eye	20.0% 2/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Eye disorders - Other, specify	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Eye pain	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Watering eyes	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Abdominal pain	30.0% 3/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	35.0% 7/20 • Number of events 11 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Ascites	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Bloating	20.0% 2/10 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	15.0% 3/20 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Constipation	40.0% 4/10 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	30.0% 6/20 • Number of events 20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Diarrhea	40.0% 4/10 • Number of events 10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 5/20 • Number of events 9 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dry mouth	20.0% 2/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	15.0% 3/20 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dyspepsia	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dysphagia	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Flatulence	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Gastroesophageal reflux disease	20.0% 2/10 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 2/20 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Gastrointestinal disorders - Other, spec	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Mucositis oral	30.0% 3/10 • Number of events 9 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	15.0% 3/20 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Nausea	90.0% 9/10 • Number of events 36 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	35.0% 7/20 • Number of events 12 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Oral pain	10.0% 1/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 2/20 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Rectal hemorrhage	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Vomiting	50.0% 5/10 • Number of events 11 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Chills	40.0% 4/10 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 2/20 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Edema limbs	20.0% 2/10 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 4/20 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Facial pain	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fatigue	90.0% 9/10 • Number of events 49 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	75.0% 15/20 • Number of events 59 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fever	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Flu like symptoms	10.0% 1/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 11 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders General disorders and administration sit	30.0% 3/10 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 15 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Localized edema	30.0% 3/10 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	15.0% 3/20 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Malaise	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Non-cardiac chest pain	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Pain	50.0% 5/10 • Number of events 6 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	15.0% 3/20 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Bladder infection	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Bronchial infection	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Infections and infestations - Other, spe	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Nail infection	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Upper respiratory infection	20.0% 2/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Urinary tract infection	30.0% 3/10 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Alanine aminotransferase increased	20.0% 2/10 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	40.0% 8/20 • Number of events 32 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Alkaline phosphatase increased	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	50.0% 10/20 • Number of events 27 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Aspartate aminotransferase increased	20.0% 2/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	45.0% 9/20 • Number of events 29 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Blood bilirubin increased	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	15.0% 3/20 • Number of events 8 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Creatinine increased	20.0% 2/10 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 2/20 • Number of events 37 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Electrocardiogram QT corrected interval	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Lymphocyte count decreased	60.0% 6/10 • Number of events 20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 2/20 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Neutrophil count decreased	60.0% 6/10 • Number of events 15 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Platelet count decreased	20.0% 2/10 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 5/20 • Number of events 7 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Weight gain	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Weight loss	30.0% 3/10 • Number of events 9 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	15.0% 3/20 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations White blood cell decreased	90.0% 9/10 • Number of events 28 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	35.0% 7/20 • Number of events 20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Acidosis	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Alkalosis	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Anorexia	50.0% 5/10 • Number of events 9 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	30.0% 6/20 • Number of events 23 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Dehydration	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 2/20 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyperglycemia	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypermagnesemia	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 2/20 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypernatremia	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyperuricemia	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	30.0% 6/20 • Number of events 11 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypoalbuminemia	20.0% 2/10 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 2/20 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypocalcemia	10.0% 1/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	15.0% 3/20 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypokalemia	60.0% 6/10 • Number of events 14 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypomagnesemia	10.0% 1/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyponatremia	50.0% 5/10 • Number of events 11 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	35.0% 7/20 • Number of events 14 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypophosphatemia	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 4/20 • Number of events 6 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Oth	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Arthralgia	30.0% 3/10 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 4/20 • Number of events 23 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Arthritis	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Back pain	40.0% 4/10 • Number of events 9 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	35.0% 7/20 • Number of events 43 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Bone pain	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 5/20 • Number of events 7 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Chest wall pain	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Flank pain	10.0% 1/10 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	30.0% 3/10 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	15.0% 3/20 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	20.0% 2/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue di	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 2/20 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Myalgia	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 4/20 • Number of events 22 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Neck pain	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 4/20 • Number of events 10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecif	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Dizziness	30.0% 3/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 2/20 • Number of events 9 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Dysgeusia	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 12 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Headache	30.0% 3/10 • Number of events 6 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 5/20 • Number of events 15 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Memory impairment	20.0% 2/10 • Number of events 7 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Peripheral sensory neuropathy	30.0% 3/10 • Number of events 16 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 4/20 • Number of events 13 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Phantom pain	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Seizure	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Somnolence	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Tremor	20.0% 2/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Psychiatric disorders Agitation	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 2/20 • Number of events 9 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Psychiatric disorders Anxiety	40.0% 4/10 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	15.0% 3/20 • Number of events 24 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Psychiatric disorders Depression	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	30.0% 6/20 • Number of events 26 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Psychiatric disorders Insomnia	20.0% 2/10 • Number of events 10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	35.0% 7/20 • Number of events 37 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Psychiatric disorders Psychiatric disorders - Other, specify	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Hematuria	40.0% 4/10 • Number of events 10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Proteinuria	40.0% 4/10 • Number of events 7 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 2/20 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Renal and urinary disorders - Other, spe	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urinary frequency	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	10.0% 2/20 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urinary tract pain	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urine discoloration	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Reproductive system and breast disorders Breast pain	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Reproductive system and breast disorders Vaginal dryness	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 8 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Atelectasis	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Bronchospasm	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Cough	80.0% 8/10 • Number of events 11 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 5/20 • Number of events 17 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	30.0% 3/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 5/20 • Number of events 8 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Hoarseness	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Nasal congestion	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal di	20.0% 2/10 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Sore throat	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Voice alteration	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Wheezing	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Alopecia	40.0% 4/10 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Dry skin	20.0% 2/10 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Hyperhidrosis	20.0% 2/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Periorbital edema	10.0% 1/10 • Number of events 6 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Pruritus	10.0% 1/10 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	15.0% 3/20 • Number of events 11 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Rash acneiform	20.0% 2/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	15.0% 3/20 • Number of events 10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	50.0% 5/10 • Number of events 7 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 5/20 • Number of events 12 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Flushing	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	5.0% 1/20 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hot flashes	0.00% 0/10 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	35.0% 7/20 • Number of events 37 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hypertension	80.0% 8/10 • Number of events 47 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	35.0% 7/20 • Number of events 59 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hypotension	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	15.0% 3/20 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Thromboembolic event	10.0% 1/10 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Vascular disorders - Other, specify	10.0% 1/10 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/20 • Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 3 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Additional Information

Paul Frankel, Ph.D.

City of Hope

Phone: 626-218-5265

Email: pfrankel@coh.org

Results disclosure agreements

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