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

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.

Time frame: 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.

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).

Time frame: 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 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.

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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 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.

Time frame: 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.