Ramucirumab: Patient Reported Outcomes in the RELAY Study

Study Design

The RELAY trial was a phase 3, global, multicenter, randomized, double-blind, placebo-controlled trial in patients (N=449) with previously untreated EGFR mutation-positive, metastatic NSCLC. All patients had an EGFR mutation of exon 19 deletion or exon 21 L858R and an ECOG PS of 0 or 1. Patients were randomly assigned in a 1:1 ratio (stratified by sex, region, EGFR mutation type, and EGFR testing method) to receive treatment with erlotinib (150 mg/day) plus ramucirumab (10 mg/kg every 2 weeks; n=224) or placebo (every 2 weeks; n=225) until disease progression or unacceptable toxicity.¹

Assessment of Patient-Focused Outcomes

Assessment Interval

Patient-focused outcomes were evaluated using ECOG PS, LCSS, and EQ-5D-5L.²

ECOG PS was assessed by the clinician

• at baseline

• before every cycle

• at the end of treatment, and

• at the 30-day follow-up visit.²

LCSS and EQ-5D-5L questionnaires were completed by the patients at the beginning of the clinic visit

• at baseline

• every other cycle, and

• at the 30-day follow-up visit.²

ECOG PS Assessment

Time-to-deterioration in ECOG PS was

• a prespecified exploratory endpoint

• defined as the time from randomization to the first observation of ECOG PS ≥2

• analyzed using the Kaplan-Meier method, and

• compared using an unstratified log rank test.²

LCSS and EQ-5D-5L Assessment

Time-to-deterioration in LCSS was

• a prespecified secondary endpoint

• defined as the time from date of randomization until the date of the first ≥15 mm increase from baseline, and

• estimated with Kaplan-Meier and Cox regression.²

The EQ-5D-5L questionnaire was

• a prespecified secondary endpoint, and

• mean scores were summarized by cycle/visit.³

Mean changes from baseline in EQ-5D-5L/LCSS scores were estimated using Mixed Effect Model Repeat Measurement regression by comparing with baseline scores.^2,3

Assessment Compliance

Patient compliance for both LCSS and EQ-5D-5L completion across all time points was high, the rates being

• 95.7% in the ramucirumab plus erlotinib arm and 96.7% in the placebo plus erlotinib arm for the LCSS, and

• 96.1% in the ramucirumab plus erlotinib arm and 96.6% in the placebo plus erlotinib arm for the EQ-5D-5L.²

At the 30-day safety follow-up visit, compliance rates were

• 74.4% in the ramucirumab plus erlotinib arm and 79.1% in the placebo plus erlotinib arm for the LCSS, and

• 74.4% in the ramucirumab plus erlotinib arm and 79.7% in the placebo plus erlotinib arm for EQ-5D-5L.²

Patient-Reported Outcome Results

ECOG PS

The majority of patients in both arms maintained an ECOG PS of 0 or 1 (94% in both arms); therefore, TTD analysis was not feasible at the time of data cut-off.²

LCSS and EQ-5D-5L

Time-to-deterioration in LCSS total score and ASBI was similar between treatment arms (LCSS total score: HR=0.962; 95% CI: 0.690-1.343; ASBI: HR=1.012; 95% CI: 0.732-1.400). Hemoptysis was the only LCSS item for which the TTD was different between arms and favored the erlotinib plus placebo arm (HR=1.987; 95% CI: 1.206-3.275).²

The mean EQ-5D-5L Index Scores across treatment cycles were similar between treatment arms and remained constant within arms over time; however, a decline in the mean scores for both treatment arms was observed at the 30-day follow-up visit.²

References

1. Nakagawa K, Garon EB, Seto T, et al. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(12):1655-1669. https://doi.org/10.1016/S1470-2045(19)30634-5

2. Yoh K, Atagi S, Reck M, et al. 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. Curr Med Res Opin. 2020;36(10):1667-1665. https://doi.org/10.1080/03007995.2020.1808781

3. Yoh K, Atagi S, Reck M, et al. Patient-focused outcomes in RELAY, a phase 3 trial of ramucirumab plus erlotinib versus placebo plus ERL in untreated EGFR-mutated metastatic NSCLC. Talk presented at: 5th Annual Meeting of the European Society of Medical Oncology Asia (ESMO Asia); November 22-24, 2019; Singapore, Singapore.

Glossary

ASBI = average symptom burden index

ECOG = Eastern Cooperative Oncology Group

EGFR = epidermal growth factor receptor

EQ-5D-5L = EuroQoL five-dimension, five-level health status questionnaire

HR = hazard ratio

LCSS = Lung Cancer Symptom Scale

NSCLC = non-small cell lung cancer

PS = performance status

QOL = quality of life

TTD = time-to-deterioration