Trial Outcomes & Findings for Study of Gemcitabine, Abraxane® Plus Placebo Versus Gemcitabine, Abraxane® Plus 1 or 2 Truncated Courses of Demcizumab in Subjects With 1st-Line Metastatic Pancreatic Ductal Adenocarcinoma (NCT NCT02289898)

Last Updated: 2020-09-28

Results Overview

Investigator assessed Kaplan-Meier estimates of progression-free survival for placebo/placebo arm and pooled demcizumab arm.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

207 participants

Primary outcome timeframe

Investigator-assessed progression-free survival time through duration of the study (2 years, 23 days).

Results posted on

2020-09-28

Participant Flow

A total of 207 subjects were randomized and 204 subjects were treated in the study.

Participant milestones

Participant milestones
Measure	Placebo/Placebo Arm Abraxane and gemcitabine plus placebo (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression.	Demcizumab/Placebo Arm Abraxane and gemcitabine plus demcizumab (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression.	Demcizumab/Demcizumab Arm Abraxane and gemcitabine plus demcizumab (3 cycles), abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus demcizumab (3 cycles), and then Abraxane and gemcitabine until disease progression.
Overall Study STARTED	68	71	65
Overall Study COMPLETED	16	18	9
Overall Study NOT COMPLETED	52	53	56

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/Placebo Arm Abraxane and gemcitabine plus placebo (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression.	Demcizumab/Placebo Arm Abraxane and gemcitabine plus demcizumab (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression.	Demcizumab/Demcizumab Arm Abraxane and gemcitabine plus demcizumab (3 cycles), abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus demcizumab (3 cycles), and then Abraxane and gemcitabine until disease progression.
Overall Study Death	5	4	3
Overall Study Physician Decision	2	5	2
Overall Study Withdrawal by Subject	0	4	1
Overall Study Adverse Event	3	5	5
Overall Study Disease progression	34	28	34
Overall Study Use of another anticancer therapy	0	0	1
Overall Study Other	8	7	10

Baseline Characteristics

Study of Gemcitabine, Abraxane® Plus Placebo Versus Gemcitabine, Abraxane® Plus 1 or 2 Truncated Courses of Demcizumab in Subjects With 1st-Line Metastatic Pancreatic Ductal Adenocarcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/Placebo Arm n=68 Participants Abraxane and gemcitabine plus placebo (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression.	Demcizumab/Placebo Arm n=71 Participants Abraxane and gemcitabine plus demcizumab (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression.	Demcizumab/Demcizumab Arm n=65 Participants Abraxane and gemcitabine plus demcizumab (3 cycles), abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus demcizumab (3 cycles), and then Abraxane and gemcitabine until disease progression.	Total n=204 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	37 Participants n=5 Participants	34 Participants n=7 Participants	30 Participants n=5 Participants	101 Participants n=4 Participants
Age, Categorical >=65 years	31 Participants n=5 Participants	37 Participants n=7 Participants	35 Participants n=5 Participants	103 Participants n=4 Participants
Age, Continuous	62 years n=5 Participants	63 years n=7 Participants	66 years n=5 Participants	63 years n=4 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	31 Participants n=7 Participants	30 Participants n=5 Participants	88 Participants n=4 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	40 Participants n=7 Participants	35 Participants n=5 Participants	116 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	60 Participants n=5 Participants	70 Participants n=7 Participants	62 Participants n=5 Participants	192 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment Canada	3 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment Belgium	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment United States	17 Participants n=5 Participants	18 Participants n=7 Participants	15 Participants n=5 Participants	50 Participants n=4 Participants
Region of Enrollment United Kingdom	3 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Region of Enrollment Australia	24 Participants n=5 Participants	13 Participants n=7 Participants	19 Participants n=5 Participants	56 Participants n=4 Participants
Region of Enrollment Spain	19 Participants n=5 Participants	31 Participants n=7 Participants	21 Participants n=5 Participants	71 Participants n=4 Participants

PRIMARY outcome

Timeframe: Investigator-assessed progression-free survival time through duration of the study (2 years, 23 days).

Population: Placebo/placebo arm and pooled demcizumab arms (ITT population).

Investigator assessed Kaplan-Meier estimates of progression-free survival for placebo/placebo arm and pooled demcizumab arm.

Outcome measures

Outcome measures
Measure	Placebo/Placebo Arm n=68 Participants Abraxane and gemcitabine plus placebo (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression.	Demcizumab/Placebo and Demcizumab/Demcizumab n=136 Participants Pooled demcizumab arms: Demcizumab/placebo arm - Abraxane and gemcitabine plus demcizumab (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression. Demcizumab/demcizumab arn - Abraxane and gemcitabine plus demcizumab (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus demcizumab (3 cycles), and then Abraxane and gemcitabine until disease progression.
Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms Progressed (event)	38 Participants	70 Participants
Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms Died (event)	5 Participants	12 Participants
Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms Censored, follow-up ended	3 Participants	7 Participants
Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms Censored, follow-up ongoing	22 Participants	47 Participants

Adverse Events

Placebo/Placebo Arm

Serious events: 40 serious events

Other events: 68 other events

Deaths: 5 deaths

Demcizumab/Placebo Arm

Serious events: 49 serious events

Other events: 71 other events

Deaths: 12 deaths

Demcizumab/Demcizumab Arm

Serious events: 34 serious events

Other events: 65 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

John, Lewicki, Chief Scientific Officer

Mereo BioPharma Group Plc.

Phone: +44333023300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Placebo/Placebo Arm n=68 participants at risk Abraxane and gemcitabine plus placebo (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression.	Demcizumab/Placebo Arm n=71 participants at risk Abraxane and gemcitabine plus demcizumab (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression.	Demcizumab/Demcizumab Arm n=65 participants at risk Abraxane and gemcitabine plus demcizumab (3 cycles), abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus demcizumab (3 cycles), and then Abraxane and gemcitabine until disease progression.
Vascular disorders Deep vein thrombosis	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Vascular disorders Embolism	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Vascular disorders Hypotension	1.5% 1/68 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	1.5% 1/68 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour rupture	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
General disorders Pyrexia	8.8% 6/68 • Number of events 6 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	4.2% 3/71 • Number of events 3 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	9.2% 6/65 • Number of events 6 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
General disorders Chest discomfort	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
General disorders Multiple organ dysfunction syndrome	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
General disorders Peripheral swelling	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
General disorders Systemic inflammatory response syndrome	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Psychiatric disorders Anxiety	1.5% 1/68 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Psychiatric disorders Confusional state	1.5% 1/68 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Psychiatric disorders Delirium	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Psychiatric disorders Mental status changes	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Injury, poisoning and procedural complications Fall	2.9% 2/68 • Number of events 2 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Injury, poisoning and procedural complications Toxicity to various agents	1.5% 1/68 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Injury, poisoning and procedural complications Anaesthetic complication	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations Blood bilirubin increased	1.5% 1/68 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations Liver function test increased	1.5% 1/68 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations Neutrophil count decreased	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations Transaminases increased	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations White blood cell count decreased	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Cardiac disorders Cardiac failure	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	2.8% 2/71 • Number of events 2 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Cardiac disorders Angina pectoris	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	2.8% 2/71 • Number of events 2 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Cardiac disorders Atrial fibrillation	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Cardiac disorders Acute myocardial infarction	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Cardiac disorders Cardiac arrest	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Cardiac disorders Cardiac failure congestive	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Blood and lymphatic system disorders Febrile neutropenia	5.9% 4/68 • Number of events 4 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Blood and lymphatic system disorders Anaemia	4.4% 3/68 • Number of events 3 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Blood and lymphatic system disorders Neutropenia	1.5% 1/68 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	3.1% 2/65 • Number of events 2 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Blood and lymphatic system disorders Haemolytic anaemia	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	2.8% 2/71 • Number of events 2 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Blood and lymphatic system disorders Haemolytic uraemic syndrome	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.5% 1/65 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	3.1% 2/65 • Number of events 2 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/71 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	3.1% 2/65 • Number of events 2 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/68 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	1.4% 1/71 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	0.00% 0/65 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.

Other adverse events
Measure	Placebo/Placebo Arm n=68 participants at risk Abraxane and gemcitabine plus placebo (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression.	Demcizumab/Placebo Arm n=71 participants at risk Abraxane and gemcitabine plus demcizumab (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression.	Demcizumab/Demcizumab Arm n=65 participants at risk Abraxane and gemcitabine plus demcizumab (3 cycles), abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus demcizumab (3 cycles), and then Abraxane and gemcitabine until disease progression.
Vascular disorders Hypertension	14.7% 10/68 • Number of events 10 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	23.9% 17/71 • Number of events 17 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	32.3% 21/65 • Number of events 21 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Vascular disorders Hypotension	16.2% 11/68 • Number of events 11 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	8.5% 6/71 • Number of events 6 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	7.7% 5/65 • Number of events 5 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Vascular disorders Deep vein thrombosis	10.3% 7/68 • Number of events 7 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	5.6% 4/71 • Number of events 4 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	13.8% 9/65 • Number of events 9 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
General disorders Fatigue	50.0% 34/68 • Number of events 34 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	43.7% 31/71 • Number of events 31 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	56.9% 37/65 • Number of events 37 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
General disorders Oedema peripheral	42.6% 29/68 • Number of events 29 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	54.9% 39/71 • Number of events 39 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	52.3% 34/65 • Number of events 34 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
General disorders Pyrexia	35.3% 24/68 • Number of events 24 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	42.3% 30/71 • Number of events 30 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	35.4% 23/65 • Number of events 23 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
General disorders Asthenia	26.5% 18/68 • Number of events 18 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	38.0% 27/71 • Number of events 27 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	30.8% 20/65 • Number of events 20 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
General disorders Chills	8.8% 6/68 • Number of events 6 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	4.2% 3/71 • Number of events 3 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	12.3% 8/65 • Number of events 8 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
General disorders Headache	17.6% 12/68 • Number of events 12 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	18.3% 13/71 • Number of events 13 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	33.8% 22/65 • Number of events 22 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Psychiatric disorders Insomnia	13.2% 9/68 • Number of events 9 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	11.3% 8/71 • Number of events 8 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	13.8% 9/65 • Number of events 9 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Psychiatric disorders Anxiety	14.7% 10/68 • Number of events 10 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	7.0% 5/71 • Number of events 5 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	4.6% 3/65 • Number of events 3 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Psychiatric disorders Depression	8.8% 6/68 • Number of events 6 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	4.2% 3/71 • Number of events 3 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	10.8% 7/65 • Number of events 7 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations Platelet count decreased	23.5% 16/68 • Number of events 16 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	28.2% 20/71 • Number of events 20 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	20.0% 13/65 • Number of events 13 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations Alanine aminotransferase increased	23.5% 16/68 • Number of events 16 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	21.1% 15/71 • Number of events 15 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	23.1% 15/65 • Number of events 15 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations Neutrophil count decreased	23.5% 16/68 • Number of events 16 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	16.9% 12/71 • Number of events 12 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	18.5% 12/65 • Number of events 12 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations Aspartate aminotransferase increased	19.1% 13/68 • Number of events 13 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	7.0% 5/71 • Number of events 5 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	18.5% 12/65 • Number of events 12 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations Brain natriuretic peptide increased	7.4% 5/68 • Number of events 5 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	15.5% 11/71 • Number of events 11 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	21.5% 14/65 • Number of events 14 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations White blood cell count decreased	13.2% 9/68 • Number of events 9 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	5.6% 4/71 • Number of events 4 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	15.4% 10/65 • Number of events 10 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations Blood alkaline phosphatase increased	7.4% 5/68 • Number of events 5 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	8.5% 6/71 • Number of events 6 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	15.4% 10/65 • Number of events 10 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations Weight decreased	11.8% 8/68 • Number of events 8 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	7.0% 5/71 • Number of events 5 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	12.3% 8/65 • Number of events 8 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations Blood bilirubin increased	8.8% 6/68 • Number of events 6 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	4.2% 3/71 • Number of events 3 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	4.6% 3/65 • Number of events 3 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Investigations Gamma-glutamyltransferase increased	7.4% 5/68 • Number of events 5 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	2.8% 2/71 • Number of events 2 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	7.7% 5/65 • Number of events 5 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Blood and lymphatic system disorders Anaemia	39.7% 27/68 • Number of events 27 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	60.6% 43/71 • Number of events 43 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	53.8% 35/65 • Number of events 35 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Blood and lymphatic system disorders Thrombocytopenia	22.1% 15/68 • Number of events 15 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	19.7% 14/71 • Number of events 14 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	24.6% 16/65 • Number of events 16 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Blood and lymphatic system disorders Neutropenia	30.9% 21/68 • Number of events 21 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	33.8% 24/71 • Number of events 24 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	38.5% 25/65 • Number of events 25 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea	26.5% 18/68 • Number of events 18 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	22.5% 16/71 • Number of events 16 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	15.4% 10/65 • Number of events 10 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Respiratory, thoracic and mediastinal disorders Epistaxis	14.7% 10/68 • Number of events 10 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	18.3% 13/71 • Number of events 13 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	26.2% 17/65 • Number of events 17 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Respiratory, thoracic and mediastinal disorders Cough	14.7% 10/68 • Number of events 10 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	16.9% 12/71 • Number of events 12 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	16.9% 11/65 • Number of events 11 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	4.4% 3/68 • Number of events 3 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	5.6% 4/71 • Number of events 4 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	12.3% 8/65 • Number of events 8 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	1.5% 1/68 • Number of events 1 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	9.9% 7/71 • Number of events 7 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	10.8% 7/65 • Number of events 7 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.4% 5/68 • Number of events 5 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	2.8% 2/71 • Number of events 2 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	7.7% 5/65 • Number of events 5 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Nervous system disorders Dysgeusia	26.5% 18/68 • Number of events 18 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	22.5% 16/71 • Number of events 16 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	26.2% 17/65 • Number of events 17 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Nervous system disorders Peripheral sensory neuropathy	23.5% 16/68 • Number of events 16 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	23.9% 17/71 • Number of events 17 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	26.2% 17/65 • Number of events 17 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Nervous system disorders Dizziness	14.7% 10/68 • Number of events 10 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	7.0% 5/71 • Number of events 5 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	10.8% 7/65 • Number of events 7 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Nervous system disorders Neurotoxicity	2.9% 2/68 • Number of events 2 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	15.5% 11/71 • Number of events 11 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	6.2% 4/65 • Number of events 4 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Eye disorders Vision blurred	4.4% 3/68 • Number of events 3 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	4.2% 3/71 • Number of events 3 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	7.7% 5/65 • Number of events 5 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Gastrointestinal disorders Nausea	61.8% 42/68 • Number of events 42 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	53.5% 38/71 • Number of events 38 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	63.1% 41/65 • Number of events 41 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Gastrointestinal disorders Diarrhoea	50.0% 34/68 • Number of events 34 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	57.7% 41/71 • Number of events 41 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	69.2% 45/65 • Number of events 45 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Gastrointestinal disorders Vomiting	39.7% 27/68 • Number of events 27 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	45.1% 32/71 • Number of events 32 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	38.5% 25/65 • Number of events 25 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.
Gastrointestinal disorders Constipation	29.4% 20/68 • Number of events 20 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	29.6% 21/71 • Number of events 21 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.	43.1% 28/65 • Number of events 28 • Adverse event data are collected from the time of randomization through 30 days after discontinuation from the study (30 dates from the date of the treatment termination visit). Total study duration: 2 years, 23 days.