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

Kazuto Nishio, Takashi Seto, Makoto Nishio, Martin Reck, Edward B. Garon, Kazuko Sakai, Koichi Goto, Terufumi Kato, Yoichi Nakanishi, Toshiaki Takahashi, Nobuyuki Yamamoto, Katsuyuki Kiura, Yuichiro Ohe, Tomohide Tamura, Carla Visseren-Grul, Bente Frimodt-Moller, Rebecca R. Hozak, Sameera R. Wijayawardana, Annamaria Zimmermann, Gosuke HommaSotaro Enatsu, Kazuhiko Nakagawa

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7 Citations (Scopus)


Introduction: The phase 3 RELAY global study (NCT02411448) revealed significant improvement in progression-free survival (PFS) with ramucirumab plus erlotinib (RAM + ERL) compared with placebo plus ERL (PL + ERL) in untreated EGFR-mutated metastatic NSCLC (hazard ratio [HR] = 0.59 [95% confidence interval (CI): 0.46–0.76, p < 0.0001]). This prespecified analysis evaluates efficacy, safety, and postprogression EGFR T790M rates of RELAY patients enrolled in Japan. Methods: Patients were randomized (1:1) to oral ERL (150 mg/d) plus intravenous RAM (10 mg/kg) or PL every 2 weeks. End points included PFS (primary), safety (secondary), and biomarker analyses (exploratory). Plasma samples collected at baseline and poststudy treatment discontinuation were evaluated for EGFR T790M mutations by next-generation sequencing. Results: The Japanese subset included 211 of 449 (47.0%) RELAY patients (RAM + ERL, n = 106; PL + ERL, n = 105). Median PFS was 19.4 versus 11.2 months for RAM + ERL versus PL + ERL treatment (HR = 0.610 [0.431–0.864]) in the Japanese intent-to-treat population, 16.6 versus 12.5 months (HR = 0.701 [0.424–1.159]) in the EGFR exon 19 deletion subgroup, and 19.4 versus 10.9 months (HR = 0.514 [0.317–0.835]) in the EGFR exon 21 L858R subgroup, respectively. Adverse events of grade 3 or above with RAM + ERL included hypertension (24.8%, all grade 3) and dermatitis acneiform (23.8%). Postprogression treatment-emergent T790M rates were similar between arms (RAM + ERL: 47%, 9 of 19 patients; PL + ERL: 50%, 20 of 40 patients). Conclusions: Clinically meaningful efficacy was observed with RAM + ERL versus PL + ERL in the RELAY Japanese subset, with no new safety concerns. Postprogression T790M rates were similar across treatment arms, indicating the addition of RAM did not affect the ERL-associated EGFR T790M rates at disease progression.

Original languageEnglish
Article number100171
JournalJTO Clinical and Research Reports
Issue number6
Publication statusPublished - Jun 2021


  • Circulating tumor DNA
  • EGFR
  • Japan
  • Non–small cell lung cancer
  • Ramucirumab

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine


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