Trial Outcomes & Findings for Everolimus and Octreotide Acetate With or Without Bevacizumab in Treating Patients With Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors That Cannot Be Removed by Surgery (NCT NCT01229943)

NCT ID: NCT01229943

Last Updated: 2022-08-04

Results Overview

Progression Free Survival (PFS) was defined as the time from study entry until disease progression or death, whichever occurs first. The median PFS was estimated using the Kaplan-Meier method. Progression was assessed per RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions (and an absolute increase of at least 0.5 cm) or the appearance of new lesions.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 150 participants
• Primary outcome timeframe: From study entry to the date of documented progression or death from any cause, up to 3 years
• Results posted on: 2022-08-04

Participant Flow

From October 2010 to October 2012, 150 participants were recruited and randomized to study treatment.

Participant milestones

Measure	Arm I (Octreotide Acetate and Everolimus) Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28 and octreotide acetate 20 mg IM on day 1.\> \> Everolimus: Given PO\> \> Octreotide Acetate: Given IM	Arm II (Octreotide Acetate, Everolimus, and Bevacizumab) Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28, octreotide acetate 20 mg IM on day 1 and bevacizumab 10 mg/kg IV on days 1 and 15.\> \> Bevacizumab: Given IV\> \> Everolimus: Given PO\> \> Octreotide Acetate: Given IM
Overall Study STARTED	75	75
Overall Study COMPLETED	57	58
Overall Study NOT COMPLETED	18	17

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Everolimus and Octreotide Acetate With or Without Bevacizumab in Treating Patients With Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors That Cannot Be Removed by Surgery

Baseline characteristics by cohort

Measure	Arm I (Octreotide Acetate and Everolimus) n=75 Participants Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28 and octreotide acetate 20 mg IM on day 1.\> \> Everolimus: Given PO\> \> Octreotide Acetate: Given IM	Arm II (Octreotide Acetate, Everolimus, and Bevacizumab) n=75 Participants Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28, octreotide acetate 20 mg IM on day 1 and bevacizumab 10 mg/kg IV on days 1 and 15.\> \> Bevacizumab: Given IV\> \> Everolimus: Given PO\> \> Octreotide Acetate: Given IM	Total n=150 Participants Total of all reporting groups
Age, Continuous	59 years n=5 Participants	58 years n=7 Participants	58.5 years n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	31 Participants n=7 Participants	66 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	44 Participants n=7 Participants	84 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	69 Participants n=5 Participants	70 Participants n=7 Participants	139 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	64 Participants n=5 Participants	61 Participants n=7 Participants	125 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Canada	5 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment United States	70 participants n=5 Participants	69 participants n=7 Participants	139 participants n=5 Participants

PRIMARY outcome

Timeframe: From study entry to the date of documented progression or death from any cause, up to 3 years

Progression Free Survival (PFS) was defined as the time from study entry until disease progression or death, whichever occurs first. The median PFS was estimated using the Kaplan-Meier method. Progression was assessed per RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions (and an absolute increase of at least 0.5 cm) or the appearance of new lesions.

Outcome measures

Measure	Arm I (Octreotide Acetate and Everolimus) n=75 Participants Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28 and octreotide acetate 20 mg IM on day 1.\> \> Everolimus: Given PO\> \> Octreotide Acetate: Given IM	Arm II (Octreotide Acetate, Everolimus, and Bevacizumab) n=75 Participants Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28, octreotide acetate 20 mg IM on day 1 and bevacizumab 10 mg/kg IV on days 1 and 15.\> \> Bevacizumab: Given IV\> \> Everolimus: Given PO\> \> Octreotide Acetate: Given IM
Progression Free Survival	14.0 months Interval 9.1 to 16.9	16.7 months Interval 12.6 to 19.7

SECONDARY outcome

Timeframe: Up to 3 years

The proportion of patients who respond (completely or partially) to each combination regimen will be estimated. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions.

Outcome measures

Measure	Arm I (Octreotide Acetate and Everolimus) n=75 Participants Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28 and octreotide acetate 20 mg IM on day 1.\> \> Everolimus: Given PO\> \> Octreotide Acetate: Given IM	Arm II (Octreotide Acetate, Everolimus, and Bevacizumab) n=75 Participants Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28, octreotide acetate 20 mg IM on day 1 and bevacizumab 10 mg/kg IV on days 1 and 15.\> \> Bevacizumab: Given IV\> \> Everolimus: Given PO\> \> Octreotide Acetate: Given IM
Overall Response Rate	12 percentage of participants	31 percentage of participants

SECONDARY outcome

Timeframe: From registration to time of death, assessed up to 3 years

Overall survival (OS) is defined as the time from study entry to death from any cause. The median OS was estimated using the Kaplan-Meier method.

Outcome measures

Measure	Arm I (Octreotide Acetate and Everolimus) n=75 Participants Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28 and octreotide acetate 20 mg IM on day 1.\> \> Everolimus: Given PO\> \> Octreotide Acetate: Given IM	Arm II (Octreotide Acetate, Everolimus, and Bevacizumab) n=75 Participants Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28, octreotide acetate 20 mg IM on day 1 and bevacizumab 10 mg/kg IV on days 1 and 15.\> \> Bevacizumab: Given IV\> \> Everolimus: Given PO\> \> Octreotide Acetate: Given IM
Overall Survival (OS)	35.0 months Interval 29.9 to The upper limit was not calculable because an insufficient number of participants reached the event at the final time point for assessment	36.7 months Interval 31.8 to The upper limit was not calculable because an insufficient number of participants reached the event at the final time point for assessment

Adverse Events

Arm I (Octreotide Acetate and Everolimus)

Serious events: 20 serious events

Other events: 73 other events

Deaths: 0 deaths

Arm II (Octreotide Acetate, Everolimus, and Bevacizumab)

Serious events: 31 serious events

Other events: 72 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm I (Octreotide Acetate and Everolimus) n=74 participants at risk Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28 and octreotide acetate 20 mg IM on day 1. Everolimus: Given PO Octreotide Acetate: Given IM	Arm II (Octreotide Acetate, Everolimus, and Bevacizumab) n=73 participants at risk Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28, octreotide acetate 20 mg IM on day 1 and bevacizumab 10 mg/kg IV on days 1 and 15. Bevacizumab: Given IV Everolimus: Given PO Octreotide Acetate: Given IM
Blood and lymphatic system disorders Anemia	5.4% 4/74 • Number of events 5 147 participants were evaluable for adverse events.	21.9% 16/73 • Number of events 25 147 participants were evaluable for adverse events.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Cardiac disorders Acute coronary syndrome	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Cardiac disorders Cardiac disorders - Other	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Cardiac disorders Chest pain - cardiac	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Cardiac disorders Heart failure	0.00% 0/74 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 5 147 participants were evaluable for adverse events.
Cardiac disorders Left ventricular systolic dysfunction	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Cardiac disorders Myocardial infarction	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Cardiac disorders Pericardial effusion	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Cardiac disorders Sinus bradycardia	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Eye disorders Blurred vision	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Eye disorders Eye pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Eye disorders Watering eyes	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Gastrointestinal disorders Abdominal distension	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Gastrointestinal disorders Abdominal pain	5.4% 4/74 • Number of events 5 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 5 147 participants were evaluable for adverse events.
Gastrointestinal disorders Ascites	0.00% 0/74 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 5 147 participants were evaluable for adverse events.
Gastrointestinal disorders Bloating	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 3 147 participants were evaluable for adverse events.
Gastrointestinal disorders Constipation	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 4 147 participants were evaluable for adverse events.
Gastrointestinal disorders Diarrhea	6.8% 5/74 • Number of events 5 147 participants were evaluable for adverse events.	19.2% 14/73 • Number of events 18 147 participants were evaluable for adverse events.
Gastrointestinal disorders Dry mouth	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Gastrointestinal disorders Duodenal obstruction	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Gastrointestinal disorders Dyspepsia	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 3 147 participants were evaluable for adverse events.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Gastrointestinal disorders Gastrointestinal disorders - Other	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 3 147 participants were evaluable for adverse events.
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Gastrointestinal disorders Gastroparesis	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Gastrointestinal disorders Hemorrhoids	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Gastrointestinal disorders Mucositis oral	5.4% 4/74 • Number of events 4 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 4 147 participants were evaluable for adverse events.
Gastrointestinal disorders Nausea	10.8% 8/74 • Number of events 8 147 participants were evaluable for adverse events.	17.8% 13/73 • Number of events 16 147 participants were evaluable for adverse events.
Gastrointestinal disorders Obstruction gastric	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Gastrointestinal disorders Pancreatitis	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Gastrointestinal disorders Vomiting	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	13.7% 10/73 • Number of events 12 147 participants were evaluable for adverse events.
General disorders Chills	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 4 147 participants were evaluable for adverse events.
General disorders Edema limbs	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	15.1% 11/73 • Number of events 15 147 participants were evaluable for adverse events.
General disorders Edema trunk	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
General disorders Fatigue	20.3% 15/74 • Number of events 18 147 participants were evaluable for adverse events.	28.8% 21/73 • Number of events 31 147 participants were evaluable for adverse events.
General disorders Fever	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 7 147 participants were evaluable for adverse events.
General disorders Malaise	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
General disorders Non-cardiac chest pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
General disorders Pain	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 5 147 participants were evaluable for adverse events.
Hepatobiliary disorders Gallbladder obstruction	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Hepatobiliary disorders Hepatic failure	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Hepatobiliary disorders Hepatic pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Hepatobiliary disorders Hepatobiliary disorders - Other	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Immune system disorders Allergic reaction	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Infections and infestations Abdominal infection	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Infections and infestations Hepatic infection	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Infections and infestations Infective myositis	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Infections and infestations Lung infection	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Infections and infestations Nail infection	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Infections and infestations Sepsis	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Skin infection	2.7% 2/74 • Number of events 3 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Infections and infestations Upper respiratory infection	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Urinary tract infection	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Wound infection	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Wound complication	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Investigations Alanine aminotransferase increased	9.5% 7/74 • Number of events 8 147 participants were evaluable for adverse events.	9.6% 7/73 • Number of events 9 147 participants were evaluable for adverse events.
Investigations Alkaline phosphatase increased	2.7% 2/74 • Number of events 3 147 participants were evaluable for adverse events.	12.3% 9/73 • Number of events 13 147 participants were evaluable for adverse events.
Investigations Aspartate aminotransferase increased	10.8% 8/74 • Number of events 9 147 participants were evaluable for adverse events.	16.4% 12/73 • Number of events 20 147 participants were evaluable for adverse events.
Investigations Blood bilirubin increased	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 8 147 participants were evaluable for adverse events.
Investigations CPK increased	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Investigations Cholesterol high	5.4% 4/74 • Number of events 4 147 participants were evaluable for adverse events.	8.2% 6/73 • Number of events 8 147 participants were evaluable for adverse events.
Investigations Creatinine increased	4.1% 3/74 • Number of events 3 147 participants were evaluable for adverse events.	12.3% 9/73 • Number of events 13 147 participants were evaluable for adverse events.
Investigations Ejection fraction decreased	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Investigations GGT increased	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Investigations Hemoglobin increased	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Investigations INR increased	0.00% 0/74 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 5 147 participants were evaluable for adverse events.
Investigations Lipase increased	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Investigations Lymphocyte count decreased	4.1% 3/74 • Number of events 4 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 4 147 participants were evaluable for adverse events.
Investigations Neutrophil count decreased	5.4% 4/74 • Number of events 5 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Investigations Platelet count decreased	5.4% 4/74 • Number of events 7 147 participants were evaluable for adverse events.	12.3% 9/73 • Number of events 16 147 participants were evaluable for adverse events.
Investigations Serum amylase increased	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Investigations Weight gain	0.00% 0/74 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 4 147 participants were evaluable for adverse events.
Investigations Weight loss	0.00% 0/74 147 participants were evaluable for adverse events.	16.4% 12/73 • Number of events 18 147 participants were evaluable for adverse events.
Investigations White blood cell decreased	0.00% 0/74 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 6 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Anorexia	6.8% 5/74 • Number of events 6 147 participants were evaluable for adverse events.	15.1% 11/73 • Number of events 13 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Dehydration	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	8.2% 6/73 • Number of events 8 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hyperglycemia	13.5% 10/74 • Number of events 12 147 participants were evaluable for adverse events.	28.8% 21/73 • Number of events 35 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypernatremia	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypertriglyceridemia	5.4% 4/74 • Number of events 5 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 6 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hyperuricemia	0.00% 0/74 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 5 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypoalbuminemia	4.1% 3/74 • Number of events 4 147 participants were evaluable for adverse events.	15.1% 11/73 • Number of events 15 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypocalcemia	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	11.0% 8/73 • Number of events 14 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypoglycemia	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 4 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypokalemia	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 7 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypomagnesemia	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	9.6% 7/73 • Number of events 8 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hyponatremia	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	15.1% 11/73 • Number of events 13 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/74 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 5 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Serum glucose decreased	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	4.1% 3/74 • Number of events 4 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 6 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Back pain	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Chest wall pain	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 5 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 3 147 participants were evaluable for adverse events.
Nervous system disorders Amnesia	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Nervous system disorders Concentration impairment	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Nervous system disorders Dizziness	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 3 147 participants were evaluable for adverse events.
Nervous system disorders Dysesthesia	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Nervous system disorders Dysgeusia	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 5 147 participants were evaluable for adverse events.
Nervous system disorders Encephalopathy	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 4 147 participants were evaluable for adverse events.
Nervous system disorders Headache	5.4% 4/74 • Number of events 4 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 5 147 participants were evaluable for adverse events.
Nervous system disorders Intracranial hemorrhage	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Nervous system disorders Lethargy	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Nervous system disorders Neuralgia	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Nervous system disorders Paresthesia	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Nervous system disorders Presyncope	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Nervous system disorders Syncope	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Psychiatric disorders Anxiety	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 4 147 participants were evaluable for adverse events.
Psychiatric disorders Confusion	0.00% 0/74 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 3 147 participants were evaluable for adverse events.
Psychiatric disorders Depression	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Psychiatric disorders Insomnia	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 3 147 participants were evaluable for adverse events.
Renal and urinary disorders Acute kidney injury	0.00% 0/74 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 6 147 participants were evaluable for adverse events.
Renal and urinary disorders Chronic kidney disease	0.00% 0/74 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 4 147 participants were evaluable for adverse events.
Renal and urinary disorders Hemoglobinuria	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Renal and urinary disorders Proteinuria	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	17.8% 13/73 • Number of events 17 147 participants were evaluable for adverse events.
Renal and urinary disorders Urinary frequency	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 3 147 participants were evaluable for adverse events.
Reproductive system and breast disorders Genital edema	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Reproductive system and breast disorders Menorrhagia	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Cough	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 3 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.1% 3/74 • Number of events 4 147 participants were evaluable for adverse events.	9.6% 7/73 • Number of events 8 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	9.6% 7/73 • Number of events 11 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Hiccups	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/74 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 5 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.4% 4/74 • Number of events 5 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Sore throat	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Voice alteration	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Alopecia	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Dry skin	2.7% 2/74 • Number of events 3 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Pruritus	4.1% 3/74 • Number of events 5 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.4% 4/74 • Number of events 4 147 participants were evaluable for adverse events.	8.2% 6/73 • Number of events 7 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Skin ulceration	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 3 147 participants were evaluable for adverse events.
Vascular disorders Hypertension	8.1% 6/74 • Number of events 7 147 participants were evaluable for adverse events.	24.7% 18/73 • Number of events 26 147 participants were evaluable for adverse events.
Vascular disorders Hypotension	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Vascular disorders Lymphedema	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Vascular disorders Thromboembolic event	0.00% 0/74 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 4 147 participants were evaluable for adverse events.

Other adverse events

Measure	Arm I (Octreotide Acetate and Everolimus) n=74 participants at risk Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28 and octreotide acetate 20 mg IM on day 1. Everolimus: Given PO Octreotide Acetate: Given IM	Arm II (Octreotide Acetate, Everolimus, and Bevacizumab) n=73 participants at risk Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28, octreotide acetate 20 mg IM on day 1 and bevacizumab 10 mg/kg IV on days 1 and 15. Bevacizumab: Given IV Everolimus: Given PO Octreotide Acetate: Given IM
Renal and urinary disorders Chronic kidney disease	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	11.0% 8/73 • Number of events 45 147 participants were evaluable for adverse events.
Renal and urinary disorders Cystitis noninfective	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Renal and urinary disorders Hematuria	5.4% 4/74 • Number of events 5 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 16 147 participants were evaluable for adverse events.
Renal and urinary disorders Hemoglobinuria	0.00% 0/74 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 41 147 participants were evaluable for adverse events.
Renal and urinary disorders Proteinuria	16.2% 12/74 • Number of events 42 147 participants were evaluable for adverse events.	63.0% 46/73 • Number of events 393 147 participants were evaluable for adverse events.
Renal and urinary disorders Renal and urinary disorders - Other	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 7 147 participants were evaluable for adverse events.
Renal and urinary disorders Renal calculi	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Renal and urinary disorders Urinary frequency	2.7% 2/74 • Number of events 11 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 44 147 participants were evaluable for adverse events.
Renal and urinary disorders Urinary retention	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 23 147 participants were evaluable for adverse events.
Renal and urinary disorders Urinary tract pain	2.7% 2/74 • Number of events 3 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Renal and urinary disorders Urinary urgency	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 22 147 participants were evaluable for adverse events.
Reproductive system and breast disorders Genital edema	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 5 147 participants were evaluable for adverse events.
Reproductive system and breast disorders Irregular menstruation	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 21 147 participants were evaluable for adverse events.
Reproductive system and breast disorders Menorrhagia	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Reproductive system and breast disorders Pelvic pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Reproductive system and breast disorders Penile pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Reproductive system and breast disorders Prostatic obstruction	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Reproductive system and breast disorders Reproductive system and breast disorders - Other	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 22 147 participants were evaluable for adverse events.
Reproductive system and breast disorders Vaginal discharge	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Reproductive system and breast disorders Vaginal dryness	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Reproductive system and breast disorders Vaginal inflammation	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	0.00% 0/74 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 9 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Bronchial stricture	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Cough	32.4% 24/74 • Number of events 60 147 participants were evaluable for adverse events.	24.7% 18/73 • Number of events 47 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	14.9% 11/74 • Number of events 30 147 participants were evaluable for adverse events.	16.4% 12/73 • Number of events 25 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Epistaxis	14.9% 11/74 • Number of events 37 147 participants were evaluable for adverse events.	63.0% 46/73 • Number of events 242 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/74 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 28 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Laryngeal hemorrhage	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 3 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Nasal congestion	2.7% 2/74 • Number of events 18 147 participants were evaluable for adverse events.	11.0% 8/73 • Number of events 36 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.1% 3/74 • Number of events 3 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 7 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pneumonitis	8.1% 6/74 • Number of events 6 147 participants were evaluable for adverse events.	12.3% 9/73 • Number of events 22 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Postnasal drip	2.7% 2/74 • Number of events 3 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 60 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Productive cough	4.1% 3/74 • Number of events 6 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 8 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	2.7% 2/74 • Number of events 9 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 39 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Sinus disorder	1.4% 1/74 • Number of events 3 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Sleep apnea	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 22 147 participants were evaluable for adverse events.
Blood and lymphatic system disorders Anemia	39.2% 29/74 • Number of events 226 147 participants were evaluable for adverse events.	54.8% 40/73 • Number of events 332 147 participants were evaluable for adverse events.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 6 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Sore throat	4.1% 3/74 • Number of events 10 147 participants were evaluable for adverse events.	13.7% 10/73 • Number of events 11 147 participants were evaluable for adverse events.
Blood and lymphatic system disorders Hemolysis	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 3 147 participants were evaluable for adverse events.
Blood and lymphatic system disorders Hemolytic uremic syndrome	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Blood and lymphatic system disorders Leukocytosis	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Blood and lymphatic system disorders Lymph node pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	1.4% 1/74 • Number of events 7 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Cardiac disorders Cardiac arrest	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Cardiac disorders Cardiac disorders - Other	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 4 147 participants were evaluable for adverse events.
Cardiac disorders Chest pain - cardiac	2.7% 2/74 • Number of events 7 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 3 147 participants were evaluable for adverse events.
Cardiac disorders Heart failure	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 12 147 participants were evaluable for adverse events.
Cardiac disorders Myocardial infarction	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Cardiac disorders Palpitations	4.1% 3/74 • Number of events 3 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Cardiac disorders Pericardial effusion	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 9 147 participants were evaluable for adverse events.
Cardiac disorders Sinus tachycardia	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 8 147 participants were evaluable for adverse events.
Ear and labyrinth disorders Ear and labyrinth disorders - Other	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 3 147 participants were evaluable for adverse events.
Ear and labyrinth disorders Ear pain	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Ear and labyrinth disorders Hearing impaired	1.4% 1/74 • Number of events 21 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 24 147 participants were evaluable for adverse events.
Ear and labyrinth disorders Middle ear inflammation	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 5 147 participants were evaluable for adverse events.
Ear and labyrinth disorders Tinnitus	2.7% 2/74 • Number of events 37 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 9 147 participants were evaluable for adverse events.
Ear and labyrinth disorders Vertigo	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Endocrine disorders Endocrine disorders - Other	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 22 147 participants were evaluable for adverse events.
Eye disorders Blurred vision	5.4% 4/74 • Number of events 36 147 participants were evaluable for adverse events.	8.2% 6/73 • Number of events 13 147 participants were evaluable for adverse events.
Eye disorders Cataract	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 4 147 participants were evaluable for adverse events.
Eye disorders Conjunctivitis	2.7% 2/74 • Number of events 5 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 5 147 participants were evaluable for adverse events.
Eye disorders Dry eye	2.7% 2/74 • Number of events 37 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 30 147 participants were evaluable for adverse events.
Eye disorders Extraocular muscle paresis	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Eye disorders Eye disorders - Other	4.1% 3/74 • Number of events 35 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 9 147 participants were evaluable for adverse events.
Eye disorders Eye pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Eye disorders Floaters	1.4% 1/74 • Number of events 19 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Eye disorders Retinal detachment	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 4 147 participants were evaluable for adverse events.
Eye disorders Watering eyes	1.4% 1/74 • Number of events 13 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Gastrointestinal disorders Abdominal distension	4.1% 3/74 • Number of events 12 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 3 147 participants were evaluable for adverse events.
Gastrointestinal disorders Abdominal pain	35.1% 26/74 • Number of events 115 147 participants were evaluable for adverse events.	34.2% 25/73 • Number of events 62 147 participants were evaluable for adverse events.
Gastrointestinal disorders Anal fistula	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 5 147 participants were evaluable for adverse events.
Gastrointestinal disorders Anal hemorrhage	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Gastrointestinal disorders Anal mucositis	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Gastrointestinal disorders Anal pain	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 25 147 participants were evaluable for adverse events.
Gastrointestinal disorders Ascites	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Gastrointestinal disorders Bloating	5.4% 4/74 • Number of events 13 147 participants were evaluable for adverse events.	13.7% 10/73 • Number of events 27 147 participants were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Voice alteration	0.00% 0/74 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 15 147 participants were evaluable for adverse events.
Gastrointestinal disorders Constipation	20.3% 15/74 • Number of events 54 147 participants were evaluable for adverse events.	23.3% 17/73 • Number of events 67 147 participants were evaluable for adverse events.
Gastrointestinal disorders Dental caries	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Gastrointestinal disorders Diarrhea	64.9% 48/74 • Number of events 244 147 participants were evaluable for adverse events.	68.5% 50/73 • Number of events 324 147 participants were evaluable for adverse events.
Gastrointestinal disorders Dry mouth	8.1% 6/74 • Number of events 67 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 9 147 participants were evaluable for adverse events.
Gastrointestinal disorders Dyspepsia	12.2% 9/74 • Number of events 65 147 participants were evaluable for adverse events.	9.6% 7/73 • Number of events 37 147 participants were evaluable for adverse events.
Gastrointestinal disorders Dysphagia	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Gastrointestinal disorders Esophageal hemorrhage	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Gastrointestinal disorders Esophageal stenosis	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Gastrointestinal disorders Fecal incontinence	1.4% 1/74 • Number of events 8 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 3 147 participants were evaluable for adverse events.
Gastrointestinal disorders Flatulence	6.8% 5/74 • Number of events 57 147 participants were evaluable for adverse events.	15.1% 11/73 • Number of events 37 147 participants were evaluable for adverse events.
Gastrointestinal disorders Gastric fistula	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Gastrointestinal disorders Gastritis	2.7% 2/74 • Number of events 3 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Gastrointestinal disorders Gastroesophageal reflux disease	5.4% 4/74 • Number of events 5 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 31 147 participants were evaluable for adverse events.
Gastrointestinal disorders Gastrointestinal disorders - Other	6.8% 5/74 • Number of events 12 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 14 147 participants were evaluable for adverse events.
Gastrointestinal disorders Gastrointestinal pain	1.4% 1/74 • Number of events 3 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 3 147 participants were evaluable for adverse events.
Gastrointestinal disorders Gingival pain	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Gastrointestinal disorders Hemorrhoidal hemorrhage	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Gastrointestinal disorders Hemorrhoids	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	12.3% 9/73 • Number of events 49 147 participants were evaluable for adverse events.
Gastrointestinal disorders Ileal fistula	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 4 147 participants were evaluable for adverse events.
Gastrointestinal disorders Lip pain	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Gastrointestinal disorders Mucositis oral	64.9% 48/74 • Number of events 280 147 participants were evaluable for adverse events.	58.9% 43/73 • Number of events 173 147 participants were evaluable for adverse events.
Gastrointestinal disorders Nausea	48.6% 36/74 • Number of events 158 147 participants were evaluable for adverse events.	52.1% 38/73 • Number of events 154 147 participants were evaluable for adverse events.
Gastrointestinal disorders Oral hemorrhage	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Gastrointestinal disorders Oral pain	2.7% 2/74 • Number of events 10 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 11 147 participants were evaluable for adverse events.
Gastrointestinal disorders Pancreatitis	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 11 147 participants were evaluable for adverse events.
Gastrointestinal disorders Periodontal disease	0.00% 0/74 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 7 147 participants were evaluable for adverse events.
Gastrointestinal disorders Rectal hemorrhage	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Gastrointestinal disorders Rectal pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 3 147 participants were evaluable for adverse events.
Gastrointestinal disorders Toothache	2.7% 2/74 • Number of events 3 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 3 147 participants were evaluable for adverse events.
Gastrointestinal disorders Vomiting	18.9% 14/74 • Number of events 32 147 participants were evaluable for adverse events.	30.1% 22/73 • Number of events 61 147 participants were evaluable for adverse events.
General disorders Chills	8.1% 6/74 • Number of events 30 147 participants were evaluable for adverse events.	17.8% 13/73 • Number of events 71 147 participants were evaluable for adverse events.
General disorders Dysmenorrhea	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
General disorders Edema face	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
General disorders Edema limbs	23.0% 17/74 • Number of events 83 147 participants were evaluable for adverse events.	34.2% 25/73 • Number of events 175 147 participants were evaluable for adverse events.
General disorders Edema trunk	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 3 147 participants were evaluable for adverse events.
General disorders Facial pain	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
General disorders Fatigue	81.1% 60/74 • Number of events 521 147 participants were evaluable for adverse events.	86.3% 63/73 • Number of events 521 147 participants were evaluable for adverse events.
General disorders Fever	12.2% 9/74 • Number of events 14 147 participants were evaluable for adverse events.	9.6% 7/73 • Number of events 12 147 participants were evaluable for adverse events.
General disorders Flu like symptoms	5.4% 4/74 • Number of events 15 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 11 147 participants were evaluable for adverse events.
General disorders Gait disturbance	2.7% 2/74 • Number of events 6 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
General disorders General disorders and administration site conditions - Other	4.1% 3/74 • Number of events 3 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 3 147 participants were evaluable for adverse events.
General disorders Localized edema	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 5 147 participants were evaluable for adverse events.
General disorders Malaise	0.00% 0/74 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 24 147 participants were evaluable for adverse events.
General disorders Neck edema	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
General disorders Non-cardiac chest pain	4.1% 3/74 • Number of events 3 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 7 147 participants were evaluable for adverse events.
General disorders Pain	16.2% 12/74 • Number of events 85 147 participants were evaluable for adverse events.	21.9% 16/73 • Number of events 59 147 participants were evaluable for adverse events.
Hepatobiliary disorders Hepatic failure	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Immune system disorders Allergic reaction	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 5 147 participants were evaluable for adverse events.
Immune system disorders Autoimmune disorder	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 16 147 participants were evaluable for adverse events.
Immune system disorders Immune system disorders - Other	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Bladder infection	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Eye infection	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Gum infection	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Hepatic infection	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Infections and infestations Infections and infestations - Other	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 11 147 participants were evaluable for adverse events.
Infections and infestations Lip infection	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Lung infection	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 3 147 participants were evaluable for adverse events.
Infections and infestations Otitis media	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Papulopustular rash	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Infections and infestations Paronychia	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 22 147 participants were evaluable for adverse events.
Infections and infestations Pharyngitis	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Prostate infection	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Salivary gland infection	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Sepsis	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Sinusitis	5.4% 4/74 • Number of events 6 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 10 147 participants were evaluable for adverse events.
Infections and infestations Skin infection	6.8% 5/74 • Number of events 8 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 7 147 participants were evaluable for adverse events.
Infections and infestations Tooth infection	4.1% 3/74 • Number of events 3 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 4 147 participants were evaluable for adverse events.
Infections and infestations Upper respiratory infection	9.5% 7/74 • Number of events 14 147 participants were evaluable for adverse events.	8.2% 6/73 • Number of events 6 147 participants were evaluable for adverse events.
Infections and infestations Urinary tract infection	4.1% 3/74 • Number of events 3 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 17 147 participants were evaluable for adverse events.
Infections and infestations Vulval infection	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Infections and infestations Wound infection	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 7 147 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Bruising	2.7% 2/74 • Number of events 7 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 5 147 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Burn	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Fall	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Fracture	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other	0.00% 0/74 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 25 147 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Intraoperative skin injury	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 3 147 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Wound complication	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 10 147 participants were evaluable for adverse events.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Investigations Alanine aminotransferase increased	37.8% 28/74 • Number of events 158 147 participants were evaluable for adverse events.	38.4% 28/73 • Number of events 172 147 participants were evaluable for adverse events.
Investigations Alkaline phosphatase increased	29.7% 22/74 • Number of events 126 147 participants were evaluable for adverse events.	43.8% 32/73 • Number of events 275 147 participants were evaluable for adverse events.
Investigations Aspartate aminotransferase increased	51.4% 38/74 • Number of events 182 147 participants were evaluable for adverse events.	54.8% 40/73 • Number of events 317 147 participants were evaluable for adverse events.
Investigations Blood bilirubin increased	4.1% 3/74 • Number of events 10 147 participants were evaluable for adverse events.	12.3% 9/73 • Number of events 33 147 participants were evaluable for adverse events.
Investigations CD4 lymphocytes decreased	0.00% 0/74 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 11 147 participants were evaluable for adverse events.
Investigations CPK increased	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Investigations Cardiac troponin I increased	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Investigations Cholesterol high	39.2% 29/74 • Number of events 178 147 participants were evaluable for adverse events.	47.9% 35/73 • Number of events 216 147 participants were evaluable for adverse events.
Investigations Creatinine increased	12.2% 9/74 • Number of events 35 147 participants were evaluable for adverse events.	24.7% 18/73 • Number of events 103 147 participants were evaluable for adverse events.
Investigations Hemoglobin increased	1.4% 1/74 • Number of events 3 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 3 147 participants were evaluable for adverse events.
Investigations INR increased	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 17 147 participants were evaluable for adverse events.
Investigations Investigations - Other	2.7% 2/74 • Number of events 9 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Investigations Lymphocyte count decreased	14.9% 11/74 • Number of events 89 147 participants were evaluable for adverse events.	11.0% 8/73 • Number of events 33 147 participants were evaluable for adverse events.
Investigations Lymphocyte count increased	5.4% 4/74 • Number of events 12 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Investigations Neutrophil count decreased	35.1% 26/74 • Number of events 74 147 participants were evaluable for adverse events.	23.3% 17/73 • Number of events 43 147 participants were evaluable for adverse events.
Investigations Pancreatic enzymes decreased	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Investigations Platelet count decreased	39.2% 29/74 • Number of events 202 147 participants were evaluable for adverse events.	46.6% 34/73 • Number of events 198 147 participants were evaluable for adverse events.
Investigations Weight gain	0.00% 0/74 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 17 147 participants were evaluable for adverse events.
Investigations Weight loss	23.0% 17/74 • Number of events 73 147 participants were evaluable for adverse events.	37.0% 27/73 • Number of events 132 147 participants were evaluable for adverse events.
Investigations White blood cell decreased	23.0% 17/74 • Number of events 99 147 participants were evaluable for adverse events.	19.2% 14/73 • Number of events 76 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Acidosis	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Anorexia	28.4% 21/74 • Number of events 104 147 participants were evaluable for adverse events.	37.0% 27/73 • Number of events 104 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Dehydration	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 5 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Glucose intolerance	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypercalcemia	6.8% 5/74 • Number of events 25 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 11 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hyperglycemia	73.0% 54/74 • Number of events 485 147 participants were evaluable for adverse events.	76.7% 56/73 • Number of events 479 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hyperkalemia	6.8% 5/74 • Number of events 11 147 participants were evaluable for adverse events.	11.0% 8/73 • Number of events 16 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypermagnesemia	2.7% 2/74 • Number of events 6 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 2 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypernatremia	0.00% 0/74 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 8 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypertriglyceridemia	48.6% 36/74 • Number of events 161 147 participants were evaluable for adverse events.	50.7% 37/73 • Number of events 249 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hyperuricemia	2.7% 2/74 • Number of events 24 147 participants were evaluable for adverse events.	11.0% 8/73 • Number of events 28 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypoalbuminemia	16.2% 12/74 • Number of events 44 147 participants were evaluable for adverse events.	31.5% 23/73 • Number of events 116 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypocalcemia	17.6% 13/74 • Number of events 46 147 participants were evaluable for adverse events.	34.2% 25/73 • Number of events 89 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypoglycemia	14.9% 11/74 • Number of events 22 147 participants were evaluable for adverse events.	8.2% 6/73 • Number of events 9 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypokalemia	12.2% 9/74 • Number of events 30 147 participants were evaluable for adverse events.	21.9% 16/73 • Number of events 53 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypomagnesemia	14.9% 11/74 • Number of events 81 147 participants were evaluable for adverse events.	19.2% 14/73 • Number of events 77 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hyponatremia	13.5% 10/74 • Number of events 42 147 participants were evaluable for adverse events.	24.7% 18/73 • Number of events 76 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Hypophosphatemia	16.2% 12/74 • Number of events 38 147 participants were evaluable for adverse events.	28.8% 21/73 • Number of events 58 147 participants were evaluable for adverse events.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	5.4% 4/74 • Number of events 10 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 8 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	10.8% 8/74 • Number of events 59 147 participants were evaluable for adverse events.	15.1% 11/73 • Number of events 111 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Arthritis	2.7% 2/74 • Number of events 11 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 11 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Back pain	24.3% 18/74 • Number of events 78 147 participants were evaluable for adverse events.	11.0% 8/73 • Number of events 39 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Bone pain	4.1% 3/74 • Number of events 5 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 6 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Chest wall pain	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Flank pain	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 7 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	9.5% 7/74 • Number of events 31 147 participants were evaluable for adverse events.	13.7% 10/73 • Number of events 58 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	6.8% 5/74 • Number of events 52 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 27 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Myalgia	10.8% 8/74 • Number of events 88 147 participants were evaluable for adverse events.	16.4% 12/73 • Number of events 45 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/74 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 19 147 participants were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	10.8% 8/74 • Number of events 49 147 participants were evaluable for adverse events.	15.1% 11/73 • Number of events 33 147 participants were evaluable for adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Nervous system disorders Cognitive disturbance	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Nervous system disorders Concentration impairment	2.7% 2/74 • Number of events 23 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Nervous system disorders Dizziness	14.9% 11/74 • Number of events 52 147 participants were evaluable for adverse events.	17.8% 13/73 • Number of events 24 147 participants were evaluable for adverse events.
Nervous system disorders Dysesthesia	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 9 147 participants were evaluable for adverse events.
Nervous system disorders Dysgeusia	12.2% 9/74 • Number of events 39 147 participants were evaluable for adverse events.	17.8% 13/73 • Number of events 75 147 participants were evaluable for adverse events.
Nervous system disorders Encephalopathy	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Nervous system disorders Headache	31.1% 23/74 • Number of events 120 147 participants were evaluable for adverse events.	43.8% 32/73 • Number of events 150 147 participants were evaluable for adverse events.
Nervous system disorders Memory impairment	1.4% 1/74 • Number of events 24 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Nervous system disorders Nervous system disorders - Other	4.1% 3/74 • Number of events 51 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Nervous system disorders Neuralgia	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 5 147 participants were evaluable for adverse events.
Nervous system disorders Paresthesia	0.00% 0/74 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 3 147 participants were evaluable for adverse events.
Nervous system disorders Peripheral motor neuropathy	2.7% 2/74 • Number of events 3 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Nervous system disorders Peripheral sensory neuropathy	9.5% 7/74 • Number of events 35 147 participants were evaluable for adverse events.	20.5% 15/73 • Number of events 42 147 participants were evaluable for adverse events.
Nervous system disorders Sinus pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Nervous system disorders Syncope	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Nervous system disorders Tremor	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 10 147 participants were evaluable for adverse events.
Psychiatric disorders Agitation	1.4% 1/74 • Number of events 3 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Psychiatric disorders Anxiety	12.2% 9/74 • Number of events 47 147 participants were evaluable for adverse events.	9.6% 7/73 • Number of events 66 147 participants were evaluable for adverse events.
Psychiatric disorders Confusion	0.00% 0/74 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 4 147 participants were evaluable for adverse events.
Psychiatric disorders Delusions	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Psychiatric disorders Depression	9.5% 7/74 • Number of events 88 147 participants were evaluable for adverse events.	11.0% 8/73 • Number of events 74 147 participants were evaluable for adverse events.
Psychiatric disorders Insomnia	23.0% 17/74 • Number of events 148 147 participants were evaluable for adverse events.	24.7% 18/73 • Number of events 146 147 participants were evaluable for adverse events.
Psychiatric disorders Libido decreased	1.4% 1/74 • Number of events 11 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Psychiatric disorders Libido increased	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Psychiatric disorders Mania	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 5 147 participants were evaluable for adverse events.
Psychiatric disorders Personality change	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Psychiatric disorders Psychiatric disorders - Other	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 3 147 participants were evaluable for adverse events.
Renal and urinary disorders Acute kidney injury	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Renal and urinary disorders Bladder spasm	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Alopecia	9.5% 7/74 • Number of events 25 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 20 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Bullous dermatitis	1.4% 1/74 • Number of events 16 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Dry skin	17.6% 13/74 • Number of events 60 147 participants were evaluable for adverse events.	21.9% 16/73 • Number of events 128 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Erythema multiforme	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Hyperhidrosis	2.7% 2/74 • Number of events 22 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Nail discoloration	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 2 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Nail loss	4.1% 3/74 • Number of events 35 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Nail ridging	1.4% 1/74 • Number of events 2 147 participants were evaluable for adverse events.	4.1% 3/73 • Number of events 7 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	2.7% 2/74 • Number of events 15 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 4 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Periorbital edema	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Pruritus	17.6% 13/74 • Number of events 76 147 participants were evaluable for adverse events.	15.1% 11/73 • Number of events 70 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Rash acneiform	5.4% 4/74 • Number of events 32 147 participants were evaluable for adverse events.	15.1% 11/73 • Number of events 87 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Rash maculo-papular	32.4% 24/74 • Number of events 66 147 participants were evaluable for adverse events.	52.1% 38/73 • Number of events 151 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Scalp pain	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	12.2% 9/74 • Number of events 67 147 participants were evaluable for adverse events.	15.1% 11/73 • Number of events 131 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	1.4% 1/74 • Number of events 5 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 6 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Skin hypopigmentation	0.00% 0/74 147 participants were evaluable for adverse events.	2.7% 2/73 • Number of events 7 147 participants were evaluable for adverse events.
Skin and subcutaneous tissue disorders Skin ulceration	5.4% 4/74 • Number of events 8 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Surgical and medical procedures Surgical and medical procedures - Other	0.00% 0/74 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 1 147 participants were evaluable for adverse events.
Vascular disorders Flushing	2.7% 2/74 • Number of events 3 147 participants were evaluable for adverse events.	1.4% 1/73 • Number of events 8 147 participants were evaluable for adverse events.
Vascular disorders Hematoma	2.7% 2/74 • Number of events 2 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Vascular disorders Hot flashes	4.1% 3/74 • Number of events 3 147 participants were evaluable for adverse events.	6.8% 5/73 • Number of events 6 147 participants were evaluable for adverse events.
Vascular disorders Hypertension	51.4% 38/74 • Number of events 226 147 participants were evaluable for adverse events.	80.8% 59/73 • Number of events 542 147 participants were evaluable for adverse events.
Vascular disorders Hypotension	1.4% 1/74 • Number of events 1 147 participants were evaluable for adverse events.	5.5% 4/73 • Number of events 5 147 participants were evaluable for adverse events.
Vascular disorders Lymphedema	1.4% 1/74 • Number of events 3 147 participants were evaluable for adverse events.	0.00% 0/73 147 participants were evaluable for adverse events.
Vascular disorders Thromboembolic event	2.7% 2/74 • Number of events 9 147 participants were evaluable for adverse events.	8.2% 6/73 • Number of events 13 147 participants were evaluable for adverse events.

Additional Information

Matthew Kulke, MD, MMSc

Dana-Farber Cancer Institute

Email: matthew_kulke@dfci.harvard.edu

Results disclosure agreements

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

Restriction type: LTE60