Nakagawa Kazuhiko, Garon Edward B, Seto Takashi, Nishio Makoto, Aix Santiago Ponce, Paz-Ares Luis, Chiu Chao-Hua, Park Keunchil, Novello Silvia, Nadal Ernest, Nishino Kazumi, Yoh Kiyotaka, Shih Jin-Yuan, Chik Jeannie Y K, Moro-Sibilot Denis, Puri Tarun, Chacko Varughese Sunoj, Frimodt-Moller Bente, Visseren-Grul Carla, Reck Martin
Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka Japan.
Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Translational Research in Oncology US Network, Los Angeles, California.
J Thorac Oncol. 2025 Apr;20(4):487-499. doi: 10.1016/j.jtho.2024.11.032. Epub 2024 Nov 30.
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.
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).
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.
In RELAY, OS was not significantly improved with similar long OS durations in both treatment arms.
ClinicalTrials.gov Identifier: NCT02411448.
RELAY是一项全球双盲、安慰剂对照的3期研究（NCT02411448），结果显示，对于未经治疗的表皮生长因子受体（EGFR）突变的转移性非小细胞肺癌（NSCLC）患者，雷莫西尤单抗（RAM）联合厄洛替尼（ERL）（RAM + ERL）在无进展生存期（主要终点）方面有统计学意义的显著改善（风险比[HR]=0.59，95%置信区间[CI]：0.46 - 0.76，p<0.0001；中位无进展生存期：19.4个月对12.4个月）。在此，我们报告意向性治疗人群的最终总生存期（OS；次要终点）结果。
2016年1月至2018年2月期间，449例符合条件的EGFR外显子19缺失或L858R突变且无中枢神经系统转移的患者被随机（1:1）分为接受ERL（150毫克/天）联合RAM（每两周10毫克/千克，N = 224）或安慰剂（N = 225）治疗。
在数据截止时，报告了297例死亡（总事件发生率 = 66%），中位随访时间为45.1个月（四分位间距：26.7 - 71.2），OS的HR为0.98（95% CI：0.78 - 1.24，p = 0.864），RAM + ERL组的中位OS为51.1个月，安慰剂 + ERL组为46.0个月。预后较差患者亚组（L858R或TP53共突变）的结果表明OS有改善趋势（L858R：HR = 0.87，95% CI：0.62 - 1.22；外显子19缺失：HR = 1.13，95% CI：0.83 -
