Trial Outcomes & Findings for Cabozantinib for Advanced Urothelial Cancer (NCT NCT01688999)

NCT ID: NCT01688999

Last Updated: 2022-10-18

Results Overview

Complete Response (CR) or Partial Response (PR) to Cabozantinib (XL184) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 69 participants
• Primary outcome timeframe: Median follow-up was 61.2 months
• Results posted on: 2022-10-18

Participant Flow

Participant milestones

Measure	Cohort 1 - (Urothelial Progressive Disease) Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 2 (Bone-only) Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 3 (Rare Histologies) Patients with non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis.
Overall Study STARTED	50	6	13
Overall Study COMPLETED	42	5	10
Overall Study NOT COMPLETED	8	1	3

Reasons for withdrawal

Measure	Cohort 1 - (Urothelial Progressive Disease) Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 2 (Bone-only) Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 3 (Rare Histologies) Patients with non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis.
Overall Study Withdrawal by Subject	5	1	1
Overall Study Adverse Event	2	0	2
Overall Study Ineligible/Not treated	1	0	0

Baseline Characteristics

Race/Ethnicity was not captured for one participant.

Baseline characteristics by cohort

Measure	Cohort 1 - (Urothelial Progressive Disease) n=50 Participants Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 2 (Bone-only) n=6 Participants Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 3 (Rare Histologies) n=13 Participants Patients with non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis.	Total n=69 Participants Total of all reporting groups
Age, Continuous	63 years n=50 Participants	66 years n=6 Participants	57 years n=13 Participants	63 years n=69 Participants
Sex: Female, Male Female	16 Participants n=50 Participants	1 Participants n=6 Participants	4 Participants n=13 Participants	21 Participants n=69 Participants
Sex: Female, Male Male	34 Participants n=50 Participants	5 Participants n=6 Participants	9 Participants n=13 Participants	48 Participants n=69 Participants
Race/Ethnicity, Customized White	41 Participants n=49 Participants • Race/Ethnicity was not captured for one participant.	5 Participants n=6 Participants • Race/Ethnicity was not captured for one participant.	10 Participants n=13 Participants • Race/Ethnicity was not captured for one participant.	56 Participants n=68 Participants • Race/Ethnicity was not captured for one participant.
Race/Ethnicity, Customized African American	4 Participants n=49 Participants • Race/Ethnicity was not captured for one participant.	0 Participants n=6 Participants • Race/Ethnicity was not captured for one participant.	3 Participants n=13 Participants • Race/Ethnicity was not captured for one participant.	7 Participants n=68 Participants • Race/Ethnicity was not captured for one participant.
Race/Ethnicity, Customized Asian	2 Participants n=49 Participants • Race/Ethnicity was not captured for one participant.	1 Participants n=6 Participants • Race/Ethnicity was not captured for one participant.	0 Participants n=13 Participants • Race/Ethnicity was not captured for one participant.	3 Participants n=68 Participants • Race/Ethnicity was not captured for one participant.
Race/Ethnicity, Customized Unknown	2 Participants n=49 Participants • Race/Ethnicity was not captured for one participant.	0 Participants n=6 Participants • Race/Ethnicity was not captured for one participant.	0 Participants n=13 Participants • Race/Ethnicity was not captured for one participant.	2 Participants n=68 Participants • Race/Ethnicity was not captured for one participant.
Region of Enrollment United States	50 participants n=50 Participants	6 participants n=6 Participants	13 participants n=13 Participants	69 participants n=69 Participants
Primary Tumor Site Bladder	30 Participants n=50 Participants	5 Participants n=6 Participants	12 Participants n=13 Participants	47 Participants n=69 Participants
Primary Tumor Site Upper tract:renal pelvis or ureter	18 Participants n=50 Participants	0 Participants n=6 Participants	1 Participants n=13 Participants	19 Participants n=69 Participants
Primary Tumor Site Bladder & upper tract	2 Participants n=50 Participants	1 Participants n=6 Participants	0 Participants n=13 Participants	3 Participants n=69 Participants

PRIMARY outcome

Timeframe: Median follow-up was 61.2 months

Population: 42/50 were analyzed in cohort 1 because 5 participants withdrew, 2 were taken off study for adverse events and 1 was ineligible. In cohort 2, 5/6 patients were analyzed because 1 withdrew; and in cohort 3, 10/13 patients were analyzed because 1 withdrew and 2 were taken off study due to adverse events.

Complete Response (CR) or Partial Response (PR) to Cabozantinib (XL184) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Measure	Cohort 1 - (Urothelial Progressive Disease) n=42 Participants Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 2 (Bone-only) n=5 Participants Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 3 (Rare Histologies) n=10 Participants Patients with non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis.
Percentage of Participants With Overall Response	19.1 percentage of participants Interval 8.6 to 34.1	NA percentage of participants The percentage and 95% CI cannot be calculated for this cohort because the participants had no measurable disease.	NA percentage of participants The percentage and 95% CI cannot be calculated for this cohort because the participants had no measurable disease.

SECONDARY outcome

Timeframe: Median follow-up was 61.2 months

Population: 42/50 were analyzed in cohort 1 because 5 participants withdrew, 2 were taken off study for adverse events and 1 was ineligible. In cohort 2, 5/6 patients were analyzed because 1 withdrew; and in cohort 3, 10/13 patients were analyzed because 1 withdrew and 2 were taken off study due to adverse events.

Measure the timing from the study start until death.

Outcome measures

Measure	Cohort 1 - (Urothelial Progressive Disease) n=42 Participants Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 2 (Bone-only) n=5 Participants Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 3 (Rare Histologies) n=10 Participants Patients with non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis.
Overall Survival	8.1 Months Interval 5.2 to 10.3	9.3 Months Interval 4.6 to 12.5	5.8 Months Interval 2.6 to 8.1

SECONDARY outcome

Timeframe: Median follow-up was 61.2 months

Population: 42/50 were analyzed in cohort 1 because 5 participants withdrew, 2 were taken off study for adverse events and 1 was ineligible. In cohort 2, 5/6 patients were analyzed because 1 withdrew; and in cohort 3, 10/13 patients were analyzed because 1 withdrew and 2 were taken off study due to adverse events.

Measure the timing of maintaining stable disease or partial response until disease progression assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest um diameters while on study.

Outcome measures

Measure	Cohort 1 - (Urothelial Progressive Disease) n=42 Participants Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 2 (Bone-only) n=5 Participants Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 3 (Rare Histologies) n=10 Participants Patients with non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis.
Progression Free Survival	3.7 Months Interval 3.1 to 6.4	5.3 Months Interval 1.8 to 8.3	2.9 Months Interval 1.8 to 3.7

SECONDARY outcome

Timeframe: Median follow-up was 61.2 months

Population: We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.

Grade 4 toxicity hypomagnesium experienced by participants related to Cabozantinib. Grade 4 toxicity is life-threatening consequences; urgent intervention indicated.

Outcome measures

Measure	Cohort 1 - (Urothelial Progressive Disease) n=68 Participants Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 2 (Bone-only) Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 3 (Rare Histologies) Patients with non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis.
Number of Participants With Grade 4 Toxicity Hypomagnesium Related to Cabozantinib	2 Participants	—	—

SECONDARY outcome

Timeframe: Median follow-up was 61.2 months

Population: We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Measure	Cohort 1 - (Urothelial Progressive Disease) n=68 Participants Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 2 (Bone-only) Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.	Cohort 3 (Rare Histologies) Patients with non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis.
Number of Participants With Serious and Non-serious Adverse Events Regardless of Attribution	67 Participants	—	—

Adverse Events

All Participants

Serious events: 66 serious events

Other events: 67 other events

Deaths: 66 deaths

Serious adverse events

Measure	All Participants n=68 participants at risk Cohort 1 - (urothelial progressive disease) Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis. Cohort 2 (Bone-only) Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis. Cohort 3 (Rare histologies) Patients with non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis.
Gastrointestinal disorders Abdominal pain	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Renal and urinary disorders Acute kidney injury	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Alanine aminotransferase increased	4.4% 3/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Alkaline phosphatase increased	5.9% 4/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Immune system disorders Anaphylaxis	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Aspartate aminotransferase increased	4.4% 3/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Back pain	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, pulmonary embolus	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Constipation	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Creatinine increased	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Diarrhea	4.4% 3/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Duodenal obstruction	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Endocrine disorders Endocrine disorders - Other, thyroiditis	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
General disorders Fatigue	8.8% 6/68 • Number of events 6 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Gastric hemorrhage	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Vascular disorders Hypertension	5.9% 4/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hypokalemia	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hypomagnesemia	2.9% 2/68 • Number of events 6 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hyponatremia	2.9% 2/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hypophosphatemia	7.4% 5/68 • Number of events 13 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Lipase increased	1.5% 1/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Lymphocyte count decreased	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Mucositis oral	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Nausea	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Neutrophil count decreased	2.9% 2/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
General disorders Pain	2.9% 2/68 • Number of events 5 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Reproductive system and breast disorders Pelvic pain	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Platelet count decreased	4.4% 3/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Renal and urinary disorders Proteinuria	4.4% 3/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Rectal fistula	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Serum amylase increased	1.5% 1/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Nervous system disorders Stroke	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Toothache	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Urinary tract infection	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Respiratory, thoracic and mediastinal disorders Voice alteration	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations White blood cell decreased	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	97.1% 66/68 • Number of events 66 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.

Other adverse events

Measure	All Participants n=68 participants at risk Cohort 1 - (urothelial progressive disease) Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis. Cohort 2 (Bone-only) Patients with bone-only urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis. Cohort 3 (Rare histologies) Patients with non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis.
Gastrointestinal disorders Abdominal pain	13.2% 9/68 • Number of events 11 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Abdominal soft tissue necrosis	1.5% 1/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Activated partial thromboplastin time prolonged	5.9% 4/68 • Number of events 6 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Alanine aminotransferase increased	51.5% 35/68 • Number of events 59 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Alkaline phosphatase increased	27.9% 19/68 • Number of events 28 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Alopecia	10.3% 7/68 • Number of events 7 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Anal pain	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Anal ulcer	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Blood and lymphatic system disorders Anemia	30.9% 21/68 • Number of events 52 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Anorexia	22.1% 15/68 • Number of events 19 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Arthralgia	5.9% 4/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Arthritis	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Aspartate aminotransferase increased	54.4% 37/68 • Number of events 59 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Back pain	20.6% 14/68 • Number of events 15 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Renal and urinary disorders Bladder spasm	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Bloating	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, hematemesis	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Blood bilirubin increased	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Buttock pain	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
General disorders Chills	5.9% 4/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Nervous system disorders Concentration impairment	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Constipation	25.0% 17/68 • Number of events 17 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Respiratory, thoracic and mediastinal disorders Cough	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Creatinine increased	26.5% 18/68 • Number of events 40 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Dehydration	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Psychiatric disorders Depression	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Diarrhea	51.5% 35/68 • Number of events 63 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Nervous system disorders Dizziness	13.2% 9/68 • Number of events 11 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Dry mouth	7.4% 5/68 • Number of events 5 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Dry skin	13.2% 9/68 • Number of events 9 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Nervous system disorders Dysgeusia	27.9% 19/68 • Number of events 20 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Dyspepsia	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	10.3% 7/68 • Number of events 9 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
General disorders Edema limbs	7.4% 5/68 • Number of events 5 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Endocrine disorders Endocrine disorders - Other, thyroiditis	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Erythema multiforme	4.4% 3/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Eye disorders Eye pain	1.5% 1/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
General disorders Fatigue	41.2% 28/68 • Number of events 48 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
General disorders Fever	11.8% 8/68 • Number of events 9 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Flank pain	7.4% 5/68 • Number of events 5 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Flatulence	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
General disorders Flu like symptoms	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Injury, poisoning and procedural complications Fracture	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Gastroesophageal reflux disease	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Gastroparesis	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Reproductive system and breast disorders Genital edema	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations GGT increased	5.9% 4/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Gingival pain	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Nervous system disorders Headache	5.9% 4/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Renal and urinary disorders Hematuria	20.6% 14/68 • Number of events 14 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Hemorrhoids	4.4% 3/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Respiratory, thoracic and mediastinal disorders Hoarseness	14.7% 10/68 • Number of events 10 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hypercalcemia	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hyperglycemia	7.4% 5/68 • Number of events 9 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hyperkalemia	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hypermagnesemia	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hypernatremia	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Vascular disorders Hypertension	14.7% 10/68 • Number of events 11 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Endocrine disorders Hyperthyroidism	10.3% 7/68 • Number of events 8 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hypoalbuminemia	22.1% 15/68 • Number of events 34 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hypocalcemia	16.2% 11/68 • Number of events 36 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hypoglycemia	5.9% 4/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hypokalemia	5.9% 4/68 • Number of events 6 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hypomagnesemia	19.1% 13/68 • Number of events 61 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hyponatremia	20.6% 14/68 • Number of events 22 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Metabolism and nutrition disorders Hypophosphatemia	42.6% 29/68 • Number of events 62 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Vascular disorders Hypotension	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Endocrine disorders Hypothyroidism	30.9% 21/68 • Number of events 27 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Infections and infestations - Other, URI	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, R. mediport	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Psychiatric disorders Insomnia	10.3% 7/68 • Number of events 7 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	4.4% 3/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Laryngitis	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Lip infection	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Lipase increased	11.8% 8/68 • Number of events 16 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
General disorders Localized edema	1.5% 1/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Lymphocyte count decreased	13.2% 9/68 • Number of events 13 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
General disorders Malaise	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Nervous system disorders Memory impairment	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Mucositis oral	20.6% 14/68 • Number of events 19 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	2.9% 2/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Myalgia	5.9% 4/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Respiratory, thoracic and mediastinal disorders Nasal congestion	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Nausea	33.8% 23/68 • Number of events 26 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Neck pain	1.5% 1/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Neutrophil count decreased	19.1% 13/68 • Number of events 23 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Non-cardiac chest pain	5.9% 4/68 • Number of events 5 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Oral dysesthesia	2.9% 2/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Oral pain	10.3% 7/68 • Number of events 7 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
General disorders Pain	14.7% 10/68 • Number of events 11 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	4.4% 3/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	54.4% 37/68 • Number of events 77 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Cardiac disorders Palpitations	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Nervous system disorders Paresthesia	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Paronychia	1.5% 1/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Reproductive system and breast disorders Pelvic pain	4.4% 3/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Nervous system disorders Peripheral sensory neuropathy	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Pharyngitis	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Platelet count decreased	48.5% 33/68 • Number of events 52 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Respiratory, thoracic and mediastinal disorders Postnasal drip	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Renal and urinary disorders Proteinuria	8.8% 6/68 • Number of events 11 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Pruritus	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Rash acneiform	10.3% 7/68 • Number of events 8 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.9% 4/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Rash pustular	2.9% 2/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Rectal fistula	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Rectal hemorrhage	4.4% 3/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Rectal pain	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Rhinitis infective	4.4% 3/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Scalp pain	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Scrotal infection	4.4% 3/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Reproductive system and breast disorders Scrotal pain	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Serum amylase increased	11.8% 8/68 • Number of events 18 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Nervous system disorders Sinus pain	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Cardiac disorders Sinus tachycardia	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Sinusitis	4.4% 3/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Skin hypopigmentation	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Skin infection	4.4% 3/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Skin ulceration	4.4% 3/68 • Number of events 3 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Respiratory, thoracic and mediastinal disorders Sore throat	5.9% 4/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Stoma site infection	1.5% 1/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Vascular disorders Thromboembolic event	5.9% 4/68 • Number of events 4 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Tooth discoloration	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Tooth infection	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Toothache	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Cardiac disorders Transient ischemic attacks	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Upper respiratory infection	5.9% 4/68 • Number of events 5 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Renal and urinary disorders Urinary frequency	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Renal and urinary disorders Urinary incontinence	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Urinary tract infection	10.3% 7/68 • Number of events 9 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Renal and urinary disorders Urinary tract pain	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Reproductive system and breast disorders Vaginal discharge	1.5% 1/68 • Number of events 6 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Vascular disorders Vascular access complication	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Vascular disorders Vascular disorders - Other, L. PE	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Respiratory, thoracic and mediastinal disorders Voice alteration	5.9% 4/68 • Number of events 5 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Gastrointestinal disorders Vomiting	10.3% 7/68 • Number of events 10 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations Weight loss	10.3% 7/68 • Number of events 8 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Investigations White blood cell decreased	32.4% 22/68 • Number of events 40 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Injury, poisoning and procedural complications Wound complication	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Wound infection	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Infections and infestations Infections and infestations - Other, umbilical fungal infection	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, abrasion - lft. ankle	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, fever blisters on lip	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Inguinal rash	1.5% 1/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, outer stoma bleeding	1.5% 1/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Pustule R. buttock	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Scrotal erythema	2.9% 2/68 • Number of events 2 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Stoma ileal conduit	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, thoracic muscle spasms	1.5% 1/68 • Number of events 1 • Median follow-up was 61.2 months All serious and non-serious adverse events are reported regardless of attribution. We did not group the adverse events by cohort because we did not expect the cohorts to experience different adverse events as they were all getting the same medication at the same dose. And 68/69 participants were analyzed because one participant was enrolled and deemed ineligible prior to treatment.

Additional Information

Dr. Andrea Apolo

National Cancer Institute

Phone: 301-480-0536

Email: apoloab@nih.gov

Results disclosure agreements

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