Trial Outcomes & Findings for Combination Chemotherapy With or Without Hypofractionated Radiation Therapy Before Surgery in Treating Patients With Pancreatic Cancer (NCT NCT02839343)

NCT ID: NCT02839343

Last Updated: 2022-05-24

Results Overview

Defined as the percentage of patients who are alive at 18 months after randomization divided by the total number of evaluable patients in each arm. An evaluable patient is defined as any patient who signed informed consent, deemed eligible by central review and received any protocol-defined treatment. 95% confidence interval will be estimated based on standard method. Chi-squared test (or Fisher's exact test if the data in contingency table is sparse) will be used to compare 18 month OS rates among treatment arms. OS within each arm will be summarized by Kaplan-Meier method. Median, 1-year and 2-year rates will be estimated based on Kaplan-Meier curves.

• Recruitment status: UNKNOWN
• Study phase: PHASE2
• Target enrollment: 126 participants
• Primary outcome timeframe: 18 months
• Results posted on: 2022-05-24

Participant Flow

Participant milestones

Measure	Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.	Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
Overall Study STARTED	70	56
Overall Study COMPLETED	65	55
Overall Study NOT COMPLETED	5	1

Reasons for withdrawal

Measure	Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.	Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
Overall Study Withdrawal by Subject	3	1
Overall Study Disease Progression Prior to Treatment	1	0
Overall Study Adverse Event	1	0

Baseline Characteristics

Combination Chemotherapy With or Without Hypofractionated Radiation Therapy Before Surgery in Treating Patients With Pancreatic Cancer

Baseline characteristics by cohort

Measure	Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) n=70 Participants Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.	Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) n=56 Participants Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.	Total n=126 Participants Total of all reporting groups
Age, Continuous	63 years n=5 Participants	66.5 years n=7 Participants	64 years n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	28 Participants n=7 Participants	62 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	28 Participants n=7 Participants	64 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	59 Participants n=5 Participants	51 Participants n=7 Participants	110 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 18 months

Population: Excluded from analysis were 6 patients that withdrew or progressed prior to treatment.

Defined as the percentage of patients who are alive at 18 months after randomization divided by the total number of evaluable patients in each arm. An evaluable patient is defined as any patient who signed informed consent, deemed eligible by central review and received any protocol-defined treatment. 95% confidence interval will be estimated based on standard method. Chi-squared test (or Fisher's exact test if the data in contingency table is sparse) will be used to compare 18 month OS rates among treatment arms. OS within each arm will be summarized by Kaplan-Meier method. Median, 1-year and 2-year rates will be estimated based on Kaplan-Meier curves.

Outcome measures

Measure	Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) n=65 Participants Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.	Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) n=55 Participants Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
Overall Survival (OS) Rate	64.6 percentage of patients	47.3 percentage of patients

SECONDARY outcome

Timeframe: 24 months

Population: Excluded from analysis were 6 patients that withdrew or progressed prior to treatment.

Defined as the percentage of patients in whom an achieved R0 resection was achieved during surgery.

Outcome measures

Measure	Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) n=65 Participants Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.	Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) n=55 Participants Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
Residual Tumor (R)0 Resection Rate	49 percentage of patients	35 percentage of patients

SECONDARY outcome

Timeframe: 4 years and 7 months

Population: Excluded from analysis were 6 patients that withdrew or progressed prior to treatment.

Defined as time from randomization to the first documentation of event where events considered are 1) disease progression, per RECIST, prior to surgery, 2) surgery with R2 resection, 3) recurrent disease following surgery, or 4) death due to any cause. Will be estimated using the method of Kaplan-Meier in each arm and compared between treatment groups using the log-rank test. The correlation between pathologic complete response (pCR) status and event-free survival time will be assessed by Cox model with landmark approach.

Outcome measures

Measure	Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) n=65 Participants Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.	Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) n=55 Participants Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
Event-free Survival	15.0 Months Interval 11.2 to 21.9	10.2 Months Interval 6.7 to 17.3

SECONDARY outcome

Timeframe: 24 months

Population: Excluded from analysis were 6 patients that withdrew or progressed prior to treatment.

Defined as the percentage of patients in whom a pCR was confirmed by histopathologic review of the surgical specimen. Chi-square test (or Fisher's exact test if the data in contingency table is sparse) will be used to compare pCR resection rate between two treatment arms. Sensitivity analysis will be conducted among patients in cohort 1) and cohort 2). The association between pCR rate and OS/progression free survival (PFS) will be assessed by log-rank test and Cox model.

Outcome measures

Measure	Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) n=65 Participants Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.	Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) n=55 Participants Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
Pathologic Complete Rate (pCR) Rate	0 percentage of patients	11 percentage of patients

SECONDARY outcome

Timeframe: 1 year

Population: All patients that were treated and assessed for adverse events

Overall adverse event rates will be compared between treatment groups using Chi-square test (or Fisher's exact test if the data in contingency table is sparse).

Outcome measures

Measure	Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) n=66 Participants Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.	Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) n=55 Participants Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
Incidence of Adverse Events Assessed Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4 and the Patient-Reported Outcomes Version of the CTCAE	66 Participants	55 Participants

Adverse Events

Arm 1 (mFOLFIRINOX + Surgery + FOLFOX)

Serious events: 33 serious events

Other events: 64 other events

Deaths: 42 deaths

Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx)

Serious events: 28 serious events

Other events: 55 other events

Deaths: 26 deaths

Serious adverse events

Measure	Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) n=66 participants at risk Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.	Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) n=55 participants at risk Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
Blood and lymphatic system disorders Anemia	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Blood and lymphatic system disorders Blood and lymph sys disorders - Oth Spec	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Blood and lymphatic system disorders Febrile neutropenia	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Cardiac disorders Atrial fibrillation	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Cardiac disorders Cardiac arrest	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Cardiac disorders Heart failure	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Cardiac disorders Sinus tachycardia	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Abdominal pain	10.6% 7/66 • Number of events 7 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	7.3% 4/55 • Number of events 6 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Ascites	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Colitis	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Diarrhea	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	7.3% 4/55 • Number of events 8 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Dysphagia	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Gastrointestinal disorders - Oth spec	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Gastroparesis	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Mucositis oral	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Nausea	4.5% 3/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	7.3% 4/55 • Number of events 6 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Vomiting	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Chills	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Death NOS	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Edema limbs	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Fatigue	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Fever	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 8 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Gen disord and admin site conds-Oth spec	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Hepatobiliary disorders Cholecystitis	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Hepatobiliary disorders Hepatic failure	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	6.1% 4/66 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Abdominal infection	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Biliary tract infection	4.5% 3/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Infections and infestations - Oth spec	10.6% 7/66 • Number of events 7 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Sepsis	4.5% 3/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Urinary tract infection	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Wound infection	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Injury, poisoning and procedural complications Inj, pois and proced complic - Oth spec	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Injury, poisoning and procedural complications Vascular access complication	1.5% 1/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Alanine aminotransferase increased	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Alkaline phosphatase increased	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Aspartate aminotransferase increased	4.5% 3/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Blood bilirubin increased	9.1% 6/66 • Number of events 6 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Lymphocyte count decreased	4.5% 3/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Neutrophil count decreased	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Platelet count decreased	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Weight loss	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations White blood cell decreased	4.5% 3/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Acidosis	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Anorexia	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Dehydration	4.5% 3/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	9.1% 5/55 • Number of events 5 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hyperglycemia	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypernatremia	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypoalbuminemia	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypokalemia	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypophosphatemia	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Metabolism, nutrition disord - Oth spec	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Musculoskeletal and connective tissue disorders Pain in extremity	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, mal, uncpec - Oth spec	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Nervous system disorders - Oth spec	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Peripheral sensory neuropathy	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Presyncope	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Seizure	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Renal and urinary disorders Acute kidney injury	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Renal and urinary disorders Renal calculi	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Chylothorax	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Laryngopharyngeal dysesthesia	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Surgical and medical procedures Surgical and medical proced - Oth spec	4.5% 3/66 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Vascular disorders Hematoma	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Vascular disorders Hypertension	4.5% 3/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Vascular disorders Superficial thrombophlebitis	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Vascular disorders Thromboembolic event	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Vascular disorders Vascular disorders - Other, specify	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.

Other adverse events

Measure	Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) n=66 participants at risk Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.	Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) n=55 participants at risk Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
Metabolism and nutrition disorders Acidosis	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Anorexia	34.8% 23/66 • Number of events 97 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	38.2% 21/55 • Number of events 86 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Dehydration	10.6% 7/66 • Number of events 11 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	14.5% 8/55 • Number of events 18 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypercalcemia	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hyperglycemia	22.7% 15/66 • Number of events 40 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	16.4% 9/55 • Number of events 28 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypermagnesemia	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypernatremia	4.5% 3/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypoalbuminemia	63.6% 42/66 • Number of events 157 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	61.8% 34/55 • Number of events 124 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypocalcemia	13.6% 9/66 • Number of events 18 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	16.4% 9/55 • Number of events 21 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypoglycemia	1.5% 1/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypokalemia	31.8% 21/66 • Number of events 56 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	38.2% 21/55 • Number of events 43 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypomagnesemia	13.6% 9/66 • Number of events 29 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	12.7% 7/55 • Number of events 13 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hyponatremia	15.2% 10/66 • Number of events 13 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	9.1% 5/55 • Number of events 8 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Hypophosphatemia	9.1% 6/66 • Number of events 6 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Metabolism and nutrition disorders Metabolism, nutrition disord - Oth spec	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Musculoskeletal and connective tissue disorders Arthralgia	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Musculoskeletal and connective tissue disorders Back pain	6.1% 4/66 • Number of events 14 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	9.1% 5/55 • Number of events 8 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Musculoskeletal and connective tissue disorders Flank pain	3.0% 2/66 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Musculoskeletal and connective tissue disorders Musculoskeletal, conn tissue - Oth spec	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Musculoskeletal and connective tissue disorders Myalgia	1.5% 1/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Musculoskeletal and connective tissue disorders Pain in extremity	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Cognitive disturbance	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Dizziness	9.1% 6/66 • Number of events 17 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	9.1% 5/55 • Number of events 15 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Dysarthria	3.0% 2/66 • Number of events 5 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Dysesthesia	4.5% 3/66 • Number of events 18 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Dysgeusia	21.2% 14/66 • Number of events 40 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	25.5% 14/55 • Number of events 58 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Headache	4.5% 3/66 • Number of events 10 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	9.1% 5/55 • Number of events 8 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Blood and lymphatic system disorders Anemia	53.0% 35/66 • Number of events 118 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	43.6% 24/55 • Number of events 112 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Blood and lymphatic system disorders Blood and lymph sys disorders - Oth Spec	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Blood and lymphatic system disorders Febrile neutropenia	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Blood and lymphatic system disorders Leukocytosis	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Cardiac disorders Cardiac disorders - Other, specify	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Cardiac disorders Sinus bradycardia	1.5% 1/66 • Number of events 8 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Cardiac disorders Sinus tachycardia	4.5% 3/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Ear and labyrinth disorders Ear and labyrinth disorders - Oth spec	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Ear and labyrinth disorders Ear pain	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Eye disorders Blurred vision	4.5% 3/66 • Number of events 5 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 16 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Eye disorders Dry eye	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Eye disorders Eye pain	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Eye disorders Scleral disorder	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Eye disorders Watering eyes	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Abdominal distension	3.0% 2/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Abdominal pain	27.3% 18/66 • Number of events 37 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	32.7% 18/55 • Number of events 36 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Ascites	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Bloating	7.6% 5/66 • Number of events 15 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	9.1% 5/55 • Number of events 26 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Constipation	24.2% 16/66 • Number of events 40 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	16.4% 9/55 • Number of events 10 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Diarrhea	84.8% 56/66 • Number of events 272 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	85.5% 47/55 • Number of events 191 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Dry mouth	13.6% 9/66 • Number of events 36 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	12.7% 7/55 • Number of events 27 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Dyspepsia	7.6% 5/66 • Number of events 10 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	9.1% 5/55 • Number of events 14 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Dysphagia	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Enterocolitis	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Esophagitis	1.5% 1/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Flatulence	7.6% 5/66 • Number of events 10 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	10.9% 6/55 • Number of events 23 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Gastritis	1.5% 1/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Gastroesophageal reflux disease	9.1% 6/66 • Number of events 16 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	9.1% 5/55 • Number of events 10 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Gastrointestinal disorders - Oth spec	3.0% 2/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 6 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Gastrointestinal fistula	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Gastroparesis	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Hemorrhoids	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Malabsorption	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Mucositis oral	13.6% 9/66 • Number of events 16 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	21.8% 12/55 • Number of events 23 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Nausea	86.4% 57/66 • Number of events 279 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	83.6% 46/55 • Number of events 222 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Oral dysesthesia	4.5% 3/66 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Oral pain	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Rectal pain	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Small intestinal mucositis	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Gastrointestinal disorders Vomiting	27.3% 18/66 • Number of events 25 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	27.3% 15/55 • Number of events 35 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Chills	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Edema limbs	9.1% 6/66 • Number of events 11 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	10.9% 6/55 • Number of events 11 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Fatigue	92.4% 61/66 • Number of events 395 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	94.5% 52/55 • Number of events 307 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Fever	7.6% 5/66 • Number of events 6 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Flu like symptoms	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Gen disord and admin site conds-Oth spec	7.6% 5/66 • Number of events 29 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 9 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Localized edema	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Malaise	3.0% 2/66 • Number of events 5 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Non-cardiac chest pain	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
General disorders Pain	6.1% 4/66 • Number of events 9 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	14.5% 8/55 • Number of events 15 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Hepatobiliary disorders Bile duct stenosis	7.6% 5/66 • Number of events 15 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	16.4% 9/55 • Number of events 40 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Immune system disorders Allergic reaction	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Biliary tract infection	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Bladder infection	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Bronchial infection	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Device related infection	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Hepatic infection	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Infections and infestations - Oth spec	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Nail infection	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Sepsis	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Sinusitis	4.5% 3/66 • Number of events 5 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Skin infection	3.0% 2/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Upper respiratory infection	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Urinary tract infection	6.1% 4/66 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Vaginal infection	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Infections and infestations Wound infection	6.1% 4/66 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Injury, poisoning and procedural complications Bruising	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Injury, poisoning and procedural complications Fall	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Injury, poisoning and procedural complications Infusion related reaction	6.1% 4/66 • Number of events 6 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Injury, poisoning and procedural complications Vascular access complication	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Injury, poisoning and procedural complications Wound dehiscence	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Alanine aminotransferase increased	39.4% 26/66 • Number of events 77 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	29.1% 16/55 • Number of events 51 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Alkaline phosphatase increased	34.8% 23/66 • Number of events 78 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	34.5% 19/55 • Number of events 83 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Aspartate aminotransferase increased	33.3% 22/66 • Number of events 53 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	25.5% 14/55 • Number of events 40 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Blood bilirubin increased	22.7% 15/66 • Number of events 24 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	20.0% 11/55 • Number of events 13 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Creatinine increased	4.5% 3/66 • Number of events 5 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Investigations - Other, specify	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Lymphocyte count decreased	10.6% 7/66 • Number of events 10 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	12.7% 7/55 • Number of events 29 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Neutrophil count decreased	24.2% 16/66 • Number of events 20 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	27.3% 15/55 • Number of events 20 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Platelet count decreased	30.3% 20/66 • Number of events 54 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	36.4% 20/55 • Number of events 55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations Weight loss	63.6% 42/66 • Number of events 162 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	60.0% 33/55 • Number of events 142 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Investigations White blood cell decreased	18.2% 12/66 • Number of events 18 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	18.2% 10/55 • Number of events 16 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Memory impairment	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Nervous system disorders - Oth spec	3.0% 2/66 • Number of events 9 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Neuralgia	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Paresthesia	9.1% 6/66 • Number of events 11 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	12.7% 7/55 • Number of events 26 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Peripheral motor neuropathy	1.5% 1/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Peripheral sensory neuropathy	74.2% 49/66 • Number of events 269 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	70.9% 39/55 • Number of events 215 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Nervous system disorders Somnolence	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Psychiatric disorders Anxiety	4.5% 3/66 • Number of events 9 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	7.3% 4/55 • Number of events 11 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Psychiatric disorders Confusion	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Psychiatric disorders Depression	4.5% 3/66 • Number of events 9 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 5 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Psychiatric disorders Insomnia	4.5% 3/66 • Number of events 8 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	9.1% 5/55 • Number of events 8 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Renal and urinary disorders Acute kidney injury	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Renal and urinary disorders Chronic kidney disease	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Renal and urinary disorders Hematuria	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Renal and urinary disorders Proteinuria	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Renal and urinary disorders Renal and urinary disorders - Oth spec	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Renal and urinary disorders Renal calculi	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Renal and urinary disorders Urinary frequency	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Renal and urinary disorders Urinary retention	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Renal and urinary disorders Urinary tract pain	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Renal and urinary disorders Urinary urgency	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Reproductive system and breast disorders Reproductive system and breast -Oth spec	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	1.5% 1/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Atelectasis	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Cough	9.1% 6/66 • Number of events 10 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.1% 4/66 • Number of events 20 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	10.9% 6/55 • Number of events 8 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Hiccups	1.5% 1/66 • Number of events 8 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Nasal congestion	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Postnasal drip	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Resp, thoracic, mediastinal - Oth spec	3.0% 2/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Sore throat	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Respiratory, thoracic and mediastinal disorders Wheezing	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Skin and subcutaneous tissue disorders Alopecia	16.7% 11/66 • Number of events 46 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	12.7% 7/55 • Number of events 30 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Skin and subcutaneous tissue disorders Dry skin	3.0% 2/66 • Number of events 11 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Skin and subcutaneous tissue disorders Erythema multiforme	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Skin and subcutaneous tissue disorders Nail discoloration	1.5% 1/66 • Number of events 13 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrm	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Skin and subcutaneous tissue disorders Pruritus	6.1% 4/66 • Number of events 6 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	4.5% 3/66 • Number of events 17 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Skin and subcutaneous tissue disorders Skin and subcut tissue disord - Oth spec	1.5% 1/66 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Surgical and medical procedures Surgical and medical proced - Oth spec	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Vascular disorders Flushing	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 2 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Vascular disorders Hematoma	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Vascular disorders Hot flashes	0.00% 0/66 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	3.6% 2/55 • Number of events 4 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Vascular disorders Hypertension	10.6% 7/66 • Number of events 28 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	5.5% 3/55 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Vascular disorders Hypotension	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	7.3% 4/55 • Number of events 5 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Vascular disorders Thromboembolic event	3.0% 2/66 • Number of events 3 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	0.00% 0/55 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.
Vascular disorders Vascular disorders - Other, specify	1.5% 1/66 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.	1.8% 1/55 • Number of events 1 • Adverse events and Serious Adverse events were collected for 2 years and all cause mortality was collected for 4 years and 7 months.

Additional Information

Frank Sinicrope

Mayo Clinic

Phone: 5072664338

Email: Sinicrope.Frank@mayo.edu

Results disclosure agreements

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