在未经治疗的egfr突变的转移性NSCLC患者中，Ramucirumab加厄洛替尼与安慰剂加厄洛替尼的最终生存结果：RELAY日本亚组

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports Pub Date : 2025-02-28 DOI:10.1016/j.jtocrr.2025.100819

Makoto Nishio MD, PhD , Takashi Seto MD, PhD , Martin Reck PhD , Edward B. Garon MD , Kazuto Nishio MD, PhD , Kazuo Kasahara MD, PhD , Kazumi Nishino MD, PhD , Miyako Satouchi MD, PhD , Kiyotaka Yoh MD , Hidetoshi Hayashi MD, PhD , Kazuko Sakai PhD , Sotaro Enatsu MD, PhD , Bente Frimodt-Møller MSc , Tomoko Matsui , Sunoj Chacko Varughese MSc , Michelle Carlsen MS , Carla Visseren-Grul MD , Kazuhiko Nakagawa MD, PhD

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引用次数: 0

摘要

无进展生存期（PFS）显著改善；3期RELAY研究中，ramucirumab （RAM）联合厄洛替尼（ERL）与安慰剂（PL）治疗未治疗的egfr突变的NSCLC(风险比[HR] = 0.59, 95%可信区间[CI]: 0.46-0.76, p <；0.0001)，包括日本子集。我们报告最新的PFS和最终的总生存期（OS）。方法患者（无中枢神经系统转移）按1:1随机分组（分层包括EGFR亮氨酸到精氨酸替代[L858R]/外显子19缺失[ex19del]）至ERL （150 mg/d）加RAM (10 mg/kg；n = 106)或PL (n = 105)，每2周静脉注射一次。这项研究没有为OS提供支持。结果在最终OS数据截止时间（中位随访= 48.2个月），RAM + ERL与PL + ERL的PFS获益持续(中位[m] PFS: 19.4 vs 11.2个月；Hr = 0.69, 95% ci: 0.51-0.93)；生存期分别为54.3个月和46.0个月（HR = 0.91, 95% CI: 0.65 ~ 1.26）。在L858R （n = 110）和ex19del （n = 100）亚组中，mOS分别为54.3个月对43.2个月（HR = 0.63, 95% CI: 0.40-0.99）和53.9个月对62.1个月（HR = 1.40, 95% CI: 0.86-2.28）。T790M进展后的发病率分别为52.0%和51.1%。接受奥西替尼作为后续治疗的患者比例为61.0%对55.2% (L858R: 58.2%对48.1%；Ex19del: 65.3% vs . 62.7%)；奥希替尼治疗的中位（范围）持续时间为16.8（0.7-58.3）个月，而20.1（2.1-77.2）个月。安全性与已知的RAM和ERL一致，毒性不会随时间增加。结论：日本亚组报告RAM加ERL可改善PFS，最大生存期大于50个月。OS因EGFR突变类型而异，L858R患者有获益指征。审判RegistrationNCT02411448

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Final Survival Outcomes With Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients With Untreated EGFR-Mutated Metastatic NSCLC: RELAY Japanese Subset

Introduction

Significant improvement in progression-free survival (PFS; primary end point) was reported in the phase 3 RELAY study with ramucirumab (RAM) plus erlotinib (ERL) versus placebo (PL) in untreated EGFR-mutated NSCLC (hazard ratio [HR] = 0.59, 95% confidence interval [CI]: 0.46–0.76, p < 0.0001), including in the Japanese subset. We report updated PFS and final overall survival (OS) for the Japanese subset.

Methods

Patients (no central nervous system metastases) were randomized 1:1 (stratification included EGFR leucine to arginine substitution [L858R]/exon 19 deletion [ex19del]) to ERL (150 mg/d) with RAM (10 mg/kg; n = 106) or PL (n = 105) intravenously every 2 weeks. The study was not powered for OS.

Results

At final OS data cutoff (median follow-up = 48.2 mo), PFS benefit was sustained with RAM plus ERL versus PL plus ERL (median [m] PFS: 19.4 versus 11.2 mo; HR = 0.69, 95% CI: 0.51–0.93); the mOS was 54.3 and 46.0 months (HR = 0.91, 95% CI: 0.65–1.26), respectively. In L858R (n = 110) and ex19del (n = 100) subgroups, the mOS was 54.3 versus 43.2 months (HR = 0.63, 95% CI: 0.40–0.99) and 53.9 versus 62.1 months (HR = 1.40, 95% CI: 0.86–2.28), respectively. T790M rates post-progression were 52.0% versus 51.1%, respectively. Osimertinib as subsequent therapy was received by 61.0% versus 55.2% patients (L858R: 58.2% versus 48.1%; ex19del: 65.3% versus 62.7%); the median (range) osimertinib treatment duration was 16.8 (0.7–58.3) versus 20.1 (2.1–77.2) months. Safety was consistent with known RAM and ERL profiles, with no increased toxicity over time.

Conclusions

The Japanese subset reported that RAM plus ERL improved PFS, and a mOS greater than 50 months was achieved. OS differed by EGFR mutation type, with an indication of benefit for patients with L858R.