RELAY: Final Overall Survival for Erlotinib Plus Ramucirumab or Placebo in Untreated, EGFR-Mutated Metastatic NSCLC
- PMID: 39622410
- DOI: 10.1016/j.jtho.2024.11.032
RELAY: Final Overall Survival for Erlotinib Plus Ramucirumab or Placebo in Untreated, EGFR-Mutated Metastatic NSCLC
Abstract
Introduction: RELAY, a global double-blind, placebo-controlled phase 3 study (NCT02411448) found statistically significant improvement in progression-free survival (primary end point) for ramucirumab (RAM) plus erlotinib (ERL) (RAM + ERL) in patients with untreated EGFR-mutated metastatic NSCLC (hazard ratio [HR] = 0.59, 95% confidence interval [CI]: 0.46-0.76, p < 0.0001; median progression-free survival: 19.4 versus 12.4 mo). Here, we report the final overall survival (OS; secondary end point) outcomes for the intention-to-treat population.
Methods: Between January 2016 and February 2018, 449 eligible patients with an EGFR exon 19del or L858R mutation and no central nervous system metastases were randomized (1:1) to ERL (150 mg/day) with RAM (10 mg/kg every two weeks, N = 224) or placebo (N = 225).
Results: At data cutoff, 297 deaths were reported (overall event rate = 66%), with a median follow-up of 45.1 months (interquartile range: 26.7-71.2), an OS HR of 0.98 (95% CI: 0.78-1.24, p = 0.864), and median OS of 51.1 months (RAM + ERL) and 46.0 months (placebo + ERL). Outcomes in subsets of patients with poor prognosis (L858R or TP53 co-mutation) suggest a directional improvement in OS (L858R: HR = 0.87, 95% CI: 0.62-1.22; exon 19del: HR = 1.13, 95% CI: 0.83-1.55; TP53 co-mutation: HR = 0.83, 95% CI: 0.58-1.19; TP53-wild-type: HR = 1.22, 95% CI: 0.87-1.72). Treatment-emergent T790M rates were similar between arms. Over 80% of patients received post-study discontinuation therapy (>50% received osimertinib in comparable numbers between arms). The safety profile for RAM + ERL was consistent with previous reports with no increased toxicity over time or new safety signals observed.
Conclusion: In RELAY, OS was not significantly improved with similar long OS durations in both treatment arms.
Clinical trial information: ClinicalTrials.gov Identifier: NCT02411448.
Keywords: EGFR mutation; Erlotinib; NSCLC; Overall survival; Ramucirumab.
Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Disclosure Dr. Nakagawa reports funding from Amgen, Ascent Development Services, Astellas Pharma, AstraZeneca, Bayer Yakuhin, BMS, Chugai, CMIC, Covance Japan, Daiichi Sankyo, Eisai, Eli Lilly Japan, EPS Corporation, EPS International, EP-CRSU, GSK, IQVIA Services JAPAN, Janssen, Japan Clinical Research Operations, Kobayashi, MRS, Merck Biopharma, Mebix, Mochida, MSD, Nippon Boehringer Ingelheim, Nippon Kayaku, Novartis Pharma, Otsuka, Pfizer Japan, Pfizer R&D Japan G.K., Pra Healthsciences, Sanofi, Shionogi &, SRL, Syneos Health Clinical, Taiho, Takeda; consulting fees from Eli Lilly Japan, Ono; honoraria from Amgen, AstraZeneca, Bayer Yakuhin, BMS, Chugai, CMIC ShiftZero, CMIC, Daiichi Sankyo, Eli Lilly Japan, Global Health Consulting Japan, Hisamitsu, Incyte biosciences Japan, Japan Clinical Research Operations, Janssen Pharmaceutical Factori, Life Technologies Japan, M3, Medical Mobile Communications, Merck Biopharma, MSD, Neo Communication, Nippon Boehringer Ingelheim, Nippon Kayaku, Novartis, Ono, Pfizer Japan, Takeda, Taiho, Taiyo Pharma, The YomiuriShimbun, Yodosha; and patents planned with Daiichi Sankyo. Dr. Garon reports funding from ABL-Bio, Arrivent, AstraZeneca, BridgeBio, BMS, Daiichi Sanko, Eli Lilly, EMD Serono, Genentech, Gilead, Iovance Biotherapeutics, Merck; Mirati Novartis, Prelude, Regeneron, Synthekine, TILT Biotherapeutics; consulting or advisory role for Abbvie, Arcus, AstraZeneca, Arrivent, Atreca, Black Diamond Therapeutics, BridgeBio, BMS, Daiichi Sankyo, EMD Serono, Eli Lilly, Gilead, GSK, Hookipa, I-Mab, LianBio, Merck, Merus, Novartis, Nuvalent, Personalis, Pfizer, Regeneron, Sanofi, Seagan, Sensei, Sumitomo, Strata, Summit, Synthekine, Xilio, Zymeworks; travel support from A2 Bio, Novartis; Sponsored Independent Medical Education for Daiichi Sankyo; and is on the scientific advisory board for LUNGevity. Dr. Seto reports honoraria from Amgen, AstraZeneca, BMS, Chugai, Eli Lilly Japan, MSD, Novartis Pharma, Ono, Pfzer Japan, Takeda, and Towa; and is an employee of Precision Medicine Asia. Dr. Nishio reports honoraria from Abbvie, AstraZeneca, Boehringer Ingelheim, BMS, Chugai, Daiichi Sankyo Healthcare, Eli Lilly, Janssen, Merck, MSD, Nippon Kayaku, Novartis Pharma, Ono, Pfizer, Taiho, Takeda. Dr. Paz-Ares reports institutional funding from AstraZeneca, BMS, MSD, Pfizer, and PharmaMar; travel support from AstraZeneca, BMS, Eli Lilly, Pfizer, and Roche, MSD; honoraria from Abbvie, Amgen, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, BMS, Celgene, Gilead, Eli Lilly, Merck Serono, Merck & Co., Inc., S.A., MSD, Mirati, Novartis, Pfizer, PharmaMar, Roche/Genentech, Sanofi, Takeda; an advisory board member for Altum Sequencing and Stab therapeutics, and leadership roles at Altum Sequencing and Stab therapeutics. Dr. Chiu reports honoraria from AstraZeneca, Boehringer Ingelheim, BMS, Chugai, Eli Lilly, Janssen, Merck KGaA, MSD, Novartis, Ono, Pfizer, Roche, and Takeda. Dr. Park reports funding from AstraZeneca, MSD; consulting or advisory role for AstraZeneca, Daiichi Sankyo, Eli Lilly, GENIUS, IMBDx, Janssen Research & Development, Merus, Zymeworks; honoraria for BeiGene, Incyte, MSD; Scientific Advisory Board: IMBDx, GENINUS, ABION. Dr. Novello reports consulting fees from Novartis and Sanofi, honoraria from Amgen, AstraZeneca, MSD, Novartis, Pfizer, Roche, Takeda, Thermofisher, and Sanofi; and is an advisory board member for AstraZeneca, MSD, Pfizer and Roche. Dr. Nadal reports research funding from Billerica, BMS, EMD Serono Research & Development Institute, Pfizer, Roche, and MA, USA, an affiliate of Merck; consulting fees from Amgen, AstraZeneca, Billerica, Boehringer Ingelheim, BMS, Daiichi Sankyo, Eli Lilly, EMD Serono Research & Development Institute, Genmab, Janssen, Johnson and Johnson, MA, MSD, Pfizer, Pierre Fabre, Qiagen, Regeneron, Roche, Sanofi, Takeda, and MA, USA, an affiliate of Merck; travel support from AstraZeneca, MSD, Pfizer, Roche and Takeda; honoraria for lectures from Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Illumina, Janssen, Johnson and Johnson, MSD, Pfizer, Qiagen, Roche, Sanofi, and Takeda; fees for participation in data safety meetings from Apollomics, Transgene and Roche. Dr. Nishino reports funding from Ono, Taiho, MSD, Abbvie, Daiichi Sankyo, Amgen, Eisai Co, Sanofi K.K., Janssen K.K., Novartis, Pfizer, Eli Lilly Japan, Merck Biopharma Co., Ltd., Takeda, Chugai, AstraZeneca; Speakers bureau for AstraZeneca, Chugai, Nippon Boehringer Ingelheim, Eli Lilly Japan, Roche Diagnostics, Novartis, Pfizer, Merk, Janssen K.K., BMS, Nippon Kayaku, Taiho; and on advisory board for AstraZeneca, Eli Lilly Japan, Pfizer. Dr. Yoh reports funding from Abbvie, Amgen, ArriVent Biopharma, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eli Lilly, MSD, Taiho, Taked; consulting fees from Boehringer Ingelheim and Abbvie; honoraria from Amgen, AstraZeneca, BMS, Chugai, Daiichi Sankyo, Kyowa kirin, Eli Lilly, MSD, Ono, Takeda. Dr. Shih reports funding from Taipei City Thoracic Disease Academic Research and Education Foundation, and Roche; consulting fees from AstraZeneca, Pfizer, MSD, Chugai, Takeda, CStone, Janssen, TTY Biopharm, Ono, and BMS; honoraria from ACTgenomics, Amgen, Genconn Biotech, AstraZeneca, Roche, Bayer, Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, MSD, Chugai, Takeda, CStone, Janssen, Tshbiopharm, TTY Biopharm, Orient EuroPharma, Ono, and BMS. Dr. Moro-Sibilot reports funding from Roche, AstraZeneca, BMS, Boehringer Ingelheim, Abbvie, Pfizer; consulting fees from Roche, AstraZeneca, BMS, MSD, Eli Lilly, Takeda, Boehringer Ingelheim, Abbvie, Becton Dickinson, Pfizer, Novartis; honoraria from Roche, BMS, MSD, Takeda; non-financial support from Roche, AstraZeneca, BMS, MSD, Eli Lilly, Takeda, Boehringer Ingelheim and Pfizer. Dr. Puri is a full-time employee of Eli Lilly and Company with stock options. Mr. Varughese is a full-time employee of Eli Lilly and Company and declares no conflict of interest. Ms. Frimodt-Moller and Dr. Visseren-Grul are full-time employees of Eli Lilly and Company with stock options. Dr. Reck reports consulting fees from Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Beigene, Eli Lilly, Mirati, MSD, Merck, Novartis, Pfizer, Sanofi, Regeneron, Roche, Takeda, and Samsung Bioepis; honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Beigene, Eli Lilly, Mirati, MSD, Merck, Novartis, Pfizer, Sanofi, Regeneron, Roche, Takeda, and Samsung Bioepis; meeting or travel support from Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Beigene, Eli Lilly, Mirati, MSD, Merck, Novartis, Pfizer, Sanofi, Regeneron, Roche, Takeda, and Samsung Bioepis; participation in Data Safety Monitoring Board or Advisory Board for Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Beigene, Eli Lilly, Mirati, MSD, Merck, Novartis, Pfizer, Sanofi, Regeneron, Roche, Takeda, and Samsung Bioepis. The remaining authors declare no conflict of interest.
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