Cyramza® (ramucirumab): Patientrapporterade resultat i RELAY-studien

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 status, and EGFR testing method) to receive treatment with erlotinib (150 mg/day) plus ramucirumab (10 mg/kg every 2 weeks; n=224) or placebo (10 mg/kg 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. ECOG PS was assessed at every visit and LCSS and EQ-5D-5L at

• baseline

• every other cycle, and

• 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, and

• estimated with Kaplan-Meier and Cox regression.²

LCSS and EQ-5D-5L Assessment

Time-to-deterioration in LCSS was

• 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

EQ-5D-5L mean scores were summarized by cycle/visit.²

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

Patient-Reported Outcome Results

ECOG PS

The majority of patients in both arms maintained an ECOG PS of 0 or 1 until PD (92.4% in the ramucirumab plus erlotinib arm and 95.1% in the erlotinib plus placebo arm); therefore, TTD analysis was not feasible.² 

LCSS and 5Q-5D-5L

Overall patient compliance for LCSS and EQ-5D-5L completion was similar between treatment arms (LCSS: 95.7% in the ramucirumab plus erlotinib arm and 96.7% in the erlotinib plus placebo arm; EQ-5D-5L: 96.1% in the ramucirumab plus erlotinib arm and 96.6% in the erlotinib plus placebo arm). Time-to-deterioration of both LCSS and ASBI was similar between treatment arms (LCSS: HR=0.96, 95% CI: 0.69-1.34; ASBI: HR=1.01, 95% CI: 0.73-1.40). Hemoptysis was the only LCSS item that was different between arms and favored the erlotinib plus placebo arm (HR=1.99, 95% CI: 1.21-3.28).² 

The authors concluded that patient health-related QOL, as measured with the EQ-5D-5L, was not adversely impacted by the addition of ramucirumab to erlotinib.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-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

PD = progressive disease

PS = performance status

QOL = quality of life

TTD = time-to-deterioration