Trial Outcomes & Findings for A Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-Small Cell Lung Cancer (NCT NCT01703091)

Last Updated: 2019-09-30

Results Overview

PFS was defined as the time from baseline until measured progressive disease (PD) or death from any cause, whichever is first. According to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), PD was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression. Participants without objectively determined PD, who were alive at the end of the follow-up period (or lost to follow-up), were censored on the date of the participant's last complete radiographic tumor assessment; if no baseline or post-baseline radiologic assessment was available, the participant was censored at the date of randomization.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

197 participants

Primary outcome timeframe

Baseline to Measured Progressive Disease or Death from Any Cause (Up to 21 Months)

Results posted on

2019-09-30

Participant Flow

Study completion was defined as death due to any cause or disease progression.

Participant milestones

Participant milestones
Measure	Ramucirumab Plus Docetaxel Ramucirumab 10 milligrams/kilogram (mg/kg) administered as an intravenous (IV) infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 milligrams/square meter (mg/m2) administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.	Placebo Plus Docetaxel Placebo administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.
Overall Study STARTED	98	99
Overall Study Received at Least One Dose of Study Drug	94	98
Overall Study COMPLETED	89	95
Overall Study NOT COMPLETED	9	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Ramucirumab Plus Docetaxel Ramucirumab 10 milligrams/kilogram (mg/kg) administered as an intravenous (IV) infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 milligrams/square meter (mg/m2) administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.	Placebo Plus Docetaxel Placebo administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.
Overall Study Adverse Event	5	3
Overall Study Physician Decision	2	1
Overall Study Withdrawal by Subject	1	0
Overall Study Sponsor Decision	1	0

Baseline Characteristics

A Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ramucirumab + Docetaxel n=94 Participants Ramucirumab 10 mg/kg administered as an intravenous (IV) infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.	Placebo + Docetaxel n=98 Participants Placebo administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.	Total n=192 Participants Total of all reporting groups
Age, Continuous	63.9 Years n=5 Participants	64.1 Years n=7 Participants	64 Years n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	27 Participants n=7 Participants	55 Participants n=5 Participants
Sex: Female, Male Male	66 Participants n=5 Participants	71 Participants n=7 Participants	137 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	94 Participants n=5 Participants	98 Participants n=7 Participants	192 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Japan	94 Participants n=5 Participants	98 Participants n=7 Participants	192 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Measured Progressive Disease or Death from Any Cause (Up to 21 Months)

Population: Full Analysis Set (FAS) population: All randomized participants who received at least one dose of study drug and whose prior therapy did not include EGFR-TKI monotherapy. The number of censored participant data for ramucirumab and placebo is 13 and 9, respectively.

Outcome measures

Outcome measures
Measure	Ramucirumab + Docetaxel n=76 Participants Ramucirumab 10 mg/kg administered as an intravenous (IV) infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.	Placebo + Docetaxel n=81 Participants Placebo administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.
Progression-Free Survival (PFS)	5.22 Months Interval 3.52 to 6.97	4.21 Months Interval 2.83 to 5.62

SECONDARY outcome

Timeframe: Baseline to Death from Any Cause (Up to 28 Months)

Population: FAS population: All randomized participants who received at least one dose of study drug and whose prior therapy did not include EGFR-TKI monotherapy. The number of censored participant data for ramucirumab and placebo is 36 and 35, respectively.

OS was defined as time from baseline to the date of death from any cause. Participants who were alive at the end of the follow-up period (or lost to follow-up) were censored on the last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	Ramucirumab + Docetaxel n=76 Participants Ramucirumab 10 mg/kg administered as an intravenous (IV) infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.	Placebo + Docetaxel n=81 Participants Placebo administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.
Overall Survival (OS)	15.15 Months Interval 12.45 to 26.55	14.65 Months Interval 11.93 to 24.44

SECONDARY outcome

Timeframe: Baseline to Measured Progressive Disease or Participant Stops Study (Up to 97 Weeks)

Population: FAS population: All randomized participants who received at least one dose of study drug and whose prior therapy did not include EGFR-TKI monotherapy.

Participants achieved an objective response if they had a best overall response of complete response (CR) or partial response (PR). According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal \[ULN\]); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. The percentage of participants who achieved an objective response equals (number of participants with CR or PR)/(number of participants assessed)\*100.

Outcome measures

Outcome measures
Measure	Ramucirumab + Docetaxel n=76 Participants Ramucirumab 10 mg/kg administered as an intravenous (IV) infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.	Placebo + Docetaxel n=81 Participants Placebo administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.
Percentage of Participants Who Achieved Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) [Objective Tumor Response Rate (ORR)]	28.9 Percentage of Participants Interval 19.1 to 40.5	18.5 Percentage of Participants Interval 10.8 to 28.7

SECONDARY outcome

Timeframe: Baseline to Measured Progressive Disease or Participant Stopped Study (Up to 97 Weeks)

Population: FAS population: All randomized participants who received at least one dose of study drug and whose prior therapy did not include EGFR-TKI monotherapy.

Participants achieved disease control if they had a best overall response of PR, CR or SD. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal \[ULN\]); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. The percentage of participants who achieved disease control equals (number of participants with CR, PR, or SD)/(number of participants assessed)\*100.

Outcome measures

Outcome measures
Measure	Ramucirumab + Docetaxel n=76 Participants Ramucirumab 10 mg/kg administered as an intravenous (IV) infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.	Placebo + Docetaxel n=81 Participants Placebo administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.
Percentage of Participants Who Achieved Best Overall Disease Response of CR, PR or Stable Disease (SD) [Disease Control Rate (DCR)]	78.9 Percentage of Participants Interval 68.1 to 87.5	70.4 Percentage of Participants Interval 59.2 to 80.0

SECONDARY outcome

Timeframe: Baseline, Day 21 Each Cycle (Cycle = 21 Days) and 30-Day Follow Up (Up to 97 Weeks)

Population: FAS population: All randomized participants who received at least one dose of study drug and whose prior therapy did not include EGFR-TKI monotherapy.

The EQ-5D is a quality-of-life instrument which allowed participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a scale from 1 to 3 (no problem, some problems, and extreme problems, respectively). These combinations of attributes were converted into a weighted Health State Index score according to a United Kingdom population-based algorithm; the possible values for the Health State Index score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension).

Outcome measures

Outcome measures
Measure	Ramucirumab + Docetaxel n=76 Participants Ramucirumab 10 mg/kg administered as an intravenous (IV) infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.	Placebo + Docetaxel n=81 Participants Placebo administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.
Change From Baseline in European Quality of Life Questionnaire - 5 Dimension (EQ-5D) Index Score Cycle 1 (n = 69, 77)	-0.024 Units on a Scale Standard Deviation 0.1928	-0.007 Units on a Scale Standard Deviation 0.1918
Change From Baseline in European Quality of Life Questionnaire - 5 Dimension (EQ-5D) Index Score Cycle 2 (n = 62, 66)	-0.021 Units on a Scale Standard Deviation 0.2190	0.006 Units on a Scale Standard Deviation 0.1961
Change From Baseline in European Quality of Life Questionnaire - 5 Dimension (EQ-5D) Index Score Cycle 3 (n = 48, 53)	-0.010 Units on a Scale Standard Deviation 0.2324	-0.005 Units on a Scale Standard Deviation 0.1891
Change From Baseline in European Quality of Life Questionnaire - 5 Dimension (EQ-5D) Index Score Cycle 4 (n = 40, 48)	0.015 Units on a Scale Standard Deviation 0.1683	-0.026 Units on a Scale Standard Deviation 0.1610
Change From Baseline in European Quality of Life Questionnaire - 5 Dimension (EQ-5D) Index Score Cycle 5 (n = 32, 40)	0.000 Units on a Scale Standard Deviation 0.2280	-0.012 Units on a Scale Standard Deviation 0.1433
Change From Baseline in European Quality of Life Questionnaire - 5 Dimension (EQ-5D) Index Score Cycle 6 (n = 28, 36)	0.035 Units on a Scale Standard Deviation 0.1741	-0.005 Units on a Scale Standard Deviation 0.1409
Change From Baseline in European Quality of Life Questionnaire - 5 Dimension (EQ-5D) Index Score Cycle 7 (n = 25 ,31)	0.002 Units on a Scale Standard Deviation 0.1857	-0.039 Units on a Scale Standard Deviation 0.1282
Change From Baseline in European Quality of Life Questionnaire - 5 Dimension (EQ-5D) Index Score Cycle 8 (n = 23, 30)	-0.053 Units on a Scale Standard Deviation 0.1750	-0.071 Units on a Scale Standard Deviation 0.1800
Change From Baseline in European Quality of Life Questionnaire - 5 Dimension (EQ-5D) Index Score 30-Day Follow Up (n= 56, 70)	-0.102 Units on a Scale Standard Deviation 0.2209	-0.132 Units on a Scale Standard Deviation 0.3344

SECONDARY outcome

Timeframe: Baseline to Measured Progressive Disease or Participant Stopped Study (up to 97 weeks)

Population: FAS population: All randomized participants who received at least one dose of study drug and whose prior therapy did not include EGFR-TKI monotherapy.

The participant-reported LCSS was a 9-item questionnaire. Six items were symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items described total symptomatic distress, interference with activity level, and global quality of life. Participant responses to each item were measured using a visual analog scale (VAS) from 0 (best outcome) to 100 (worst outcome). The Average Symptom Burden Index (ASBI) was the mean of the 6 symptom-specific items in the LCSS. The Total LCSS was the mean of all 9 LCSS items. Maximum improvement in LCSS scores, ASBI, and Total LCSS score was the largest decrease from baseline for each variable, which was the smallest (most negative or smallest positive) non-missing value among all change from baseline values for each variable.

Outcome measures

Outcome measures
Measure	Ramucirumab + Docetaxel n=76 Participants Ramucirumab 10 mg/kg administered as an intravenous (IV) infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.	Placebo + Docetaxel n=81 Participants Placebo administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Loss of Appetite (n=73, 79)	-12.5 Millimeter Standard Deviation 26.23	-16.2 Millimeter Standard Deviation 21.45
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Fatigue (n=73, 80)	-4.9 Millimeter Standard Deviation 25.38	-7.8 Millimeter Standard Deviation 23.59
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Cough (n=73, 80)	-4.4 Millimeter Standard Deviation 23.10	-18.3 Millimeter Standard Deviation 23.83
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Overall Symptoms (n=73, 80)	-7.1 Millimeter Standard Deviation 26.10	-11.5 Millimeter Standard Deviation 19.83
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Interference with Activity Level (n=73, 80)	-8.4 Millimeter Standard Deviation 25.84	-11.9 Millimeter Standard Deviation 21.98
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Quality of Life (n=73, 80)	-11.7 Millimeter Standard Deviation 28.06	-12.7 Millimeter Standard Deviation 21.06
Change From Baseline in Lung Cancer Symptom Scale (LCSS) ASBI (n=73, 79)	-2.82 Millimeter Standard Deviation 14.93	-6.93 Millimeter Standard Deviation 12.06
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Dyspnea (n=73, 80)	-4.7 Millimeter Standard Deviation 23.09	-8.7 Millimeter Standard Deviation 20.16
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Hemoptysis (n=73, 80)	-1.2 Millimeter Standard Deviation 12.83	-3.7 Millimeter Standard Deviation 17.25
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Pain (n=73, 80)	-9.6 Millimeter Standard Deviation 23.66	-9.0 Millimeter Standard Deviation 21.52
Change From Baseline in Lung Cancer Symptom Scale (LCSS) Total LCSS (n=73, 79)	-3.20 Millimeter Standard Deviation 15.64	-7.13 Millimeter Standard Deviation 11.74

Adverse Events

Ramucirumab + Docetaxel

Serious events: 30 serious events

Other events: 94 other events

Deaths: 0 deaths

Placebo + Docetaxel

Serious events: 31 serious events

Other events: 98 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Ramucirumab + Docetaxel n=94 participants at risk Ramucirumab 10 mg/kg administered as an intravenous (IV) infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.	Placebo + Docetaxel n=98 participants at risk Placebo administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.
Blood and lymphatic system disorders Febrile neutropenia	8.5% 8/94 • Number of events 8 All randomized participants who received at least one dose of study drug.	6.1% 6/98 • Number of events 6 All randomized participants who received at least one dose of study drug.
Blood and lymphatic system disorders Splenomegaly	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Anorectal disorder	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Gastric ulcer haemorrhage	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Ileus	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Ileus paralytic	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Large intestine perforation	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Stomatitis	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
General disorders General physical health deterioration	2.1% 2/94 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
General disorders Malaise	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Hepatobiliary disorders Drug-induced liver injury	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Hepatobiliary disorders Hepatic cirrhosis	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Infections and infestations Bronchopulmonary aspergillosis	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Infections and infestations Diverticulitis	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Infections and infestations Herpes zoster	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Infections and infestations Infection	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Infections and infestations Lung abscess	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Infections and infestations Lung infection	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	3.1% 3/98 • Number of events 3 All randomized participants who received at least one dose of study drug.
Infections and infestations Pneumonia	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Infections and infestations Sepsis	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Infections and infestations Septic shock	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	4.3% 4/94 • Number of events 4 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypercalcaemia	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Chondrocalcinosis pyrophosphate	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphangiosis carcinomatosa	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	2.1% 2/94 • Number of events 2 All randomized participants who received at least one dose of study drug.	4.1% 4/98 • Number of events 4 All randomized participants who received at least one dose of study drug.
Nervous system disorders Cerebral infarction	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Nervous system disorders Cognitive disorder	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Bladder disorder	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	2.1% 2/94 • Number of events 2 All randomized participants who received at least one dose of study drug.	2.0% 2/98 • Number of events 2 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/94 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.1% 2/94 • Number of events 2 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumothorax	3.2% 3/94 • Number of events 3 All randomized participants who received at least one dose of study drug.	3.1% 3/98 • Number of events 3 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	1.1% 1/94 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.

Measure	Ramucirumab + Docetaxel n=94 participants at risk Ramucirumab 10 mg/kg administered as an intravenous (IV) infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.	Placebo + Docetaxel n=98 participants at risk Placebo administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle. Docetaxel 60 mg/m2 administered as an IV infusion over approximately 60 minutes on Day 1 of every 21-day cycle.
Blood and lymphatic system disorders Anaemia	39.4% 37/94 • Number of events 60 All randomized participants who received at least one dose of study drug.	41.8% 41/98 • Number of events 68 All randomized participants who received at least one dose of study drug.
Blood and lymphatic system disorders Febrile neutropenia	27.7% 26/94 • Number of events 29 All randomized participants who received at least one dose of study drug.	15.3% 15/98 • Number of events 17 All randomized participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukopenia	13.8% 13/94 • Number of events 33 All randomized participants who received at least one dose of study drug.	24.5% 24/98 • Number of events 63 All randomized participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	18.1% 17/94 • Number of events 46 All randomized participants who received at least one dose of study drug.	30.6% 30/98 • Number of events 70 All randomized participants who received at least one dose of study drug.
Eye disorders Eye discharge	5.3% 5/94 • Number of events 5 All randomized participants who received at least one dose of study drug.	1.0% 1/98 • Number of events 1 All randomized participants who received at least one dose of study drug.
Eye disorders Lacrimation increased	8.5% 8/94 • Number of events 8 All randomized participants who received at least one dose of study drug.	4.1% 4/98 • Number of events 4 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	7.4% 7/94 • Number of events 7 All randomized participants who received at least one dose of study drug.	6.1% 6/98 • Number of events 6 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	3.2% 3/94 • Number of events 4 All randomized participants who received at least one dose of study drug.	5.1% 5/98 • Number of events 5 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	16.0% 15/94 • Number of events 34 All randomized participants who received at least one dose of study drug.	28.6% 28/98 • Number of events 36 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	33.0% 31/94 • Number of events 50 All randomized participants who received at least one dose of study drug.	23.5% 23/98 • Number of events 50 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	36.2% 34/94 • Number of events 52 All randomized participants who received at least one dose of study drug.	39.8% 39/98 • Number of events 52 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Periodontal disease	6.4% 6/94 • Number of events 7 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Stomatitis	53.2% 50/94 • Number of events 92 All randomized participants who received at least one dose of study drug.	31.6% 31/98 • Number of events 41 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	14.9% 14/94 • Number of events 15 All randomized participants who received at least one dose of study drug.	22.4% 22/98 • Number of events 31 All randomized participants who received at least one dose of study drug.
General disorders Face oedema	16.0% 15/94 • Number of events 18 All randomized participants who received at least one dose of study drug.	7.1% 7/98 • Number of events 7 All randomized participants who received at least one dose of study drug.
General disorders Fatigue	30.9% 29/94 • Number of events 45 All randomized participants who received at least one dose of study drug.	25.5% 25/98 • Number of events 47 All randomized participants who received at least one dose of study drug.
General disorders Malaise	45.7% 43/94 • Number of events 97 All randomized participants who received at least one dose of study drug.	48.0% 47/98 • Number of events 85 All randomized participants who received at least one dose of study drug.
General disorders Oedema peripheral	36.2% 34/94 • Number of events 38 All randomized participants who received at least one dose of study drug.	28.6% 28/98 • Number of events 33 All randomized participants who received at least one dose of study drug.
General disorders Pyrexia	33.0% 31/94 • Number of events 54 All randomized participants who received at least one dose of study drug.	26.5% 26/98 • Number of events 45 All randomized participants who received at least one dose of study drug.
Immune system disorders Hypersensitivity	3.2% 3/94 • Number of events 3 All randomized participants who received at least one dose of study drug.	5.1% 5/98 • Number of events 15 All randomized participants who received at least one dose of study drug.
Infections and infestations Conjunctivitis	6.4% 6/94 • Number of events 6 All randomized participants who received at least one dose of study drug.	2.0% 2/98 • Number of events 2 All randomized participants who received at least one dose of study drug.
Infections and infestations Lung infection	4.3% 4/94 • Number of events 4 All randomized participants who received at least one dose of study drug.	5.1% 5/98 • Number of events 5 All randomized participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	8.5% 8/94 • Number of events 9 All randomized participants who received at least one dose of study drug.	11.2% 11/98 • Number of events 11 All randomized participants who received at least one dose of study drug.
Infections and infestations Paronychia	6.4% 6/94 • Number of events 6 All randomized participants who received at least one dose of study drug.	7.1% 7/98 • Number of events 7 All randomized participants who received at least one dose of study drug.
Infections and infestations Pharyngitis	8.5% 8/94 • Number of events 9 All randomized participants who received at least one dose of study drug.	2.0% 2/98 • Number of events 2 All randomized participants who received at least one dose of study drug.
Infections and infestations Skin infection	5.3% 5/94 • Number of events 5 All randomized participants who received at least one dose of study drug.	3.1% 3/98 • Number of events 4 All randomized participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	9.6% 9/94 • Number of events 14 All randomized participants who received at least one dose of study drug.	5.1% 5/98 • Number of events 7 All randomized participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	16.0% 15/94 • Number of events 17 All randomized participants who received at least one dose of study drug.	2.0% 2/98 • Number of events 2 All randomized participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	20.2% 19/94 • Number of events 26 All randomized participants who received at least one dose of study drug.	6.1% 6/98 • Number of events 12 All randomized participants who received at least one dose of study drug.
Investigations Blood bilirubin increased	3.2% 3/94 • Number of events 4 All randomized participants who received at least one dose of study drug.	6.1% 6/98 • Number of events 11 All randomized participants who received at least one dose of study drug.
Investigations Gamma-glutamyltransferase increased	5.3% 5/94 • Number of events 5 All randomized participants who received at least one dose of study drug.	2.0% 2/98 • Number of events 2 All randomized participants who received at least one dose of study drug.
Investigations Lymphocyte count decreased	6.4% 6/94 • Number of events 16 All randomized participants who received at least one dose of study drug.	11.2% 11/98 • Number of events 43 All randomized participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	77.7% 73/94 • Number of events 281 All randomized participants who received at least one dose of study drug.	70.4% 69/98 • Number of events 219 All randomized participants who received at least one dose of study drug.
Investigations Platelet count decreased	23.4% 22/94 • Number of events 42 All randomized participants who received at least one dose of study drug.	14.3% 14/98 • Number of events 22 All randomized participants who received at least one dose of study drug.
Investigations Weight decreased	5.3% 5/94 • Number of events 6 All randomized participants who received at least one dose of study drug.	9.2% 9/98 • Number of events 12 All randomized participants who received at least one dose of study drug.
Investigations White blood cell count decreased	77.7% 73/94 • Number of events 261 All randomized participants who received at least one dose of study drug.	69.4% 68/98 • Number of events 226 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	57.4% 54/94 • Number of events 90 All randomized participants who received at least one dose of study drug.	52.0% 51/98 • Number of events 92 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	30.9% 29/94 • Number of events 44 All randomized participants who received at least one dose of study drug.	21.4% 21/98 • Number of events 32 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypophosphataemia	2.1% 2/94 • Number of events 4 All randomized participants who received at least one dose of study drug.	5.1% 5/98 • Number of events 5 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	19.1% 18/94 • Number of events 24 All randomized participants who received at least one dose of study drug.	14.3% 14/98 • Number of events 27 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	8.5% 8/94 • Number of events 9 All randomized participants who received at least one dose of study drug.	13.3% 13/98 • Number of events 17 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	20.2% 19/94 • Number of events 32 All randomized participants who received at least one dose of study drug.	18.4% 18/98 • Number of events 26 All randomized participants who received at least one dose of study drug.
Nervous system disorders Dizziness	4.3% 4/94 • Number of events 4 All randomized participants who received at least one dose of study drug.	6.1% 6/98 • Number of events 7 All randomized participants who received at least one dose of study drug.
Nervous system disorders Dysgeusia	26.6% 25/94 • Number of events 36 All randomized participants who received at least one dose of study drug.	26.5% 26/98 • Number of events 34 All randomized participants who received at least one dose of study drug.
Nervous system disorders Headache	12.8% 12/94 • Number of events 16 All randomized participants who received at least one dose of study drug.	16.3% 16/98 • Number of events 22 All randomized participants who received at least one dose of study drug.
Nervous system disorders Peripheral sensory neuropathy	21.3% 20/94 • Number of events 20 All randomized participants who received at least one dose of study drug.	27.6% 27/98 • Number of events 27 All randomized participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	18.1% 17/94 • Number of events 18 All randomized participants who received at least one dose of study drug.	18.4% 18/98 • Number of events 21 All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Proteinuria	29.8% 28/94 • Number of events 36 All randomized participants who received at least one dose of study drug.	8.2% 8/98 • Number of events 11 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	6.4% 6/94 • Number of events 6 All randomized participants who received at least one dose of study drug.	11.2% 11/98 • Number of events 12 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.4% 6/94 • Number of events 6 All randomized participants who received at least one dose of study drug.	9.2% 9/98 • Number of events 9 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	48.9% 46/94 • Number of events 90 All randomized participants who received at least one dose of study drug.	18.4% 18/98 • Number of events 21 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	6.4% 6/94 • Number of events 9 All randomized participants who received at least one dose of study drug.	6.1% 6/98 • Number of events 6 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Hiccups	8.5% 8/94 • Number of events 24 All randomized participants who received at least one dose of study drug.	9.2% 9/98 • Number of events 24 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.3% 5/94 • Number of events 6 All randomized participants who received at least one dose of study drug.	4.1% 4/98 • Number of events 4 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	14.9% 14/94 • Number of events 14 All randomized participants who received at least one dose of study drug.	6.1% 6/98 • Number of events 6 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	67.0% 63/94 • Number of events 63 All randomized participants who received at least one dose of study drug.	62.2% 61/98 • Number of events 62 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis acneiform	9.6% 9/94 • Number of events 9 All randomized participants who received at least one dose of study drug.	12.2% 12/98 • Number of events 13 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dry skin	18.1% 17/94 • Number of events 18 All randomized participants who received at least one dose of study drug.	17.3% 17/98 • Number of events 17 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Nail discolouration	23.4% 22/94 • Number of events 22 All randomized participants who received at least one dose of study drug.	19.4% 19/98 • Number of events 19 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Nail ridging	5.3% 5/94 • Number of events 5 All randomized participants who received at least one dose of study drug.	7.1% 7/98 • Number of events 7 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Onychomadesis	7.4% 7/94 • Number of events 7 All randomized participants who received at least one dose of study drug.	6.1% 6/98 • Number of events 6 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	11.7% 11/94 • Number of events 11 All randomized participants who received at least one dose of study drug.	2.0% 2/98 • Number of events 2 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	8.5% 8/94 • Number of events 9 All randomized participants who received at least one dose of study drug.	7.1% 7/98 • Number of events 8 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	7.4% 7/94 • Number of events 8 All randomized participants who received at least one dose of study drug.	12.2% 12/98 • Number of events 16 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash maculo-papular	2.1% 2/94 • Number of events 2 All randomized participants who received at least one dose of study drug.	6.1% 6/98 • Number of events 8 All randomized participants who received at least one dose of study drug.
Vascular disorders Flushing	4.3% 4/94 • Number of events 12 All randomized participants who received at least one dose of study drug.	7.1% 7/98 • Number of events 12 All randomized participants who received at least one dose of study drug.
Vascular disorders Hypertension	10.6% 10/94 • Number of events 10 All randomized participants who received at least one dose of study drug.	0.00% 0/98 All randomized participants who received at least one dose of study drug.
Vascular disorders Vasculitis	2.1% 2/94 • Number of events 2 All randomized participants who received at least one dose of study drug.	9.2% 9/98 • Number of events 11 All randomized participants who received at least one dose of study drug.