Patient-reported outcomes in RELAY, a phase 3 trial of ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic non-small-cell lung cancer

Figures & data

Table 1. LCSS scores: baseline and change from baseline – difference between treatment arms.

	Baseline LCSS Scores^a				MMRM Analysis of Change from Baseline Ramucirumab–Placebo^b^,c
	Ramucirumab Arm		Placebo Arm		LS Mean (SE)	p Value^d
	(N = 224)		(N = 225)
	n	Mean ± SD	n	Mean ± SD
Loss of appetite	216	24.7 ± 24.4	218	26.1 ± 22.9	−0.52 (1.68)	.757
Fatigue	216	30.8 ± 26.5	218	26.7 ± 25.9	−0.60 (1.61)	.711
Cough	216	29.6 ± 29.9	218	20.3 ± 24.1	2.42 (1.35)	.073
Shortness of breath	216	20.3 ± 23.9	218	18.2 ± 22.4	1.78 (1.40)	.204
Blood in sputum	216	2.6 ± 10.9	216	1.6 ± 7.9	1.63 (0.60)	.007
Pain	216	18.3 ± 23.5	216	16.6 ± 23.8	0.12 (1.39)	.930
Symptom distress	216	21.9 ± 24.3	217	19.8 ± 24.9	−0.98 (1.43)	.494
Activity level	216	22.8 ± 25.4	217	22.7 ± 27.6	−0.53 (1.62)	.744
Quality of life	216	27.4 ± 23.5	217	30.0 ± 25.7	−0.78 (1.58)	.624
Total LCSS	216	22.0 ± 15.0	216	20.2 ± 16.0	0.13 (1.08)	.908
ASBI	216	21.0 ± 15.2	216	18.3 ± 14.6	0.58 (1.02)	.572

Abbreviations. ASBI, Average Symptom Burden Index; LCSS, Lung Cancer Symptom Scale; LS, Least square; MMRM, Mixed-effect model repeated-measures regression; SD, Standard deviation; SE, Standard error of the LS mean.

^aScores range from 0 to 100 with lower scores representing lower symptom burden or less interference with health-related quality of life.

^bComparison of treatment group marginal means (the mean of the LS means averaged over the cycles). Model: response = baseline score + treatment + cycle + treatment × cycle (with patient nested in treatment as random effect in the model).

^cAt Cycle 2, n = 209 for the ramucirumab/erlotinib arm and n = 214 for the placebo/erlotinib arm (n = 213 for some LCSS items). At subsequent cycles, n decreases for both arms as patients discontinue from the study.

^dp Value for treatment comparison is based on LS means.

Figure 1. Time to deterioration (TtD) in LCSS. A forest plot is shown to display the TtD hazard ratios for the LCSS data for the six symptom-specific items and three summary items, as well as the Total Score (mean of the nine LCSS items) and the Average Symptom Burden Index (ASBI; mean of the 6 symptom items). Abbreviations. HR, Hazard ratio; PboErl, Placebo + erlotinib treatment arm; RamErl, Ramucirumab + erlotinib treatment arm.

Figure 2. Kaplan–Meier estimates of time to deterioration for (A) Total LCSS and (B) ASBI. Abbreviations. HR, Hazard ratio; NR, Not reached; PboErl, Placebo + erlotinib treatment arm; RamErl, Ramucirumab + erlotinib treatment arm.

Figure 3. LCSS Total Score by cycle. For the 100 point LCSS scale, the mean LCSS Total Score ± SD is shown for each cycle for the two treatment arms. Higher mean LCSS scores indicate worse symptom burden. Abbreviations. PboErl, Placebo + erlotinib treatment arm; RamErl, Ramucirumab + erlotinib treatment arm.

Figure 4. Mean EQ-5D Index Scores (±SD) across treatment cycles. Patients completed the EQ-5D at baseline (Cycle/Visit 0) and every other subsequent visit. The mean EQ-5D Index score for each treatment arm is shown over time, including the 30 day post-discontinuation follow-up visit. Abbreviations. PboErl, Placebo + erlotinib treatment arm; RamErl, Ramucirumab + erlotinib treatment arm.

Data availability statement

Eli Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the USA and EU and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once they are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, and blank or annotated case report forms will be provided in a secure data sharing environment for up to 2 years per proposal. For details on submitting a request, see the Vivli website: www.vivli.org.