Abstract
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 language | English |
---|---|
Article number | 100171 |
Journal | JTO Clinical and Research Reports |
Volume | 2 |
Issue number | 6 |
DOIs | |
Publication status | Published - Jun 2021 |
Externally published | Yes |
Keywords
- Circulating tumor DNA
- EGFR
- Japan
- Non–small cell lung cancer
- Ramucirumab
ASJC Scopus subject areas
- Oncology
- Pulmonary and Respiratory Medicine
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Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients With Untreated Metastatic EGFR-Mutated NSCLC : RELAY Japanese Subset. / Nishio, Kazuto; Seto, Takashi; Nishio, Makoto; Reck, Martin; Garon, Edward B.; Sakai, Kazuko; Goto, Koichi; Kato, Terufumi; Nakanishi, Yoichi; Takahashi, Toshiaki; Yamamoto, Nobuyuki; Kiura, Katsuyuki; Ohe, Yuichiro; Tamura, Tomohide; Visseren-Grul, Carla; Frimodt-Moller, Bente; Hozak, Rebecca R.; Wijayawardana, Sameera R.; Zimmermann, Annamaria; Homma, Gosuke; Enatsu, Sotaro; Nakagawa, Kazuhiko.
In: JTO Clinical and Research Reports, Vol. 2, No. 6, 100171, 06.2021.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients With Untreated Metastatic EGFR-Mutated NSCLC
T2 - RELAY Japanese Subset
AU - Nishio, Kazuto
AU - Seto, Takashi
AU - Nishio, Makoto
AU - Reck, Martin
AU - Garon, Edward B.
AU - Sakai, Kazuko
AU - Goto, Koichi
AU - Kato, Terufumi
AU - Nakanishi, Yoichi
AU - Takahashi, Toshiaki
AU - Yamamoto, Nobuyuki
AU - Kiura, Katsuyuki
AU - Ohe, Yuichiro
AU - Tamura, Tomohide
AU - Visseren-Grul, Carla
AU - Frimodt-Moller, Bente
AU - Hozak, Rebecca R.
AU - Wijayawardana, Sameera R.
AU - Zimmermann, Annamaria
AU - Homma, Gosuke
AU - Enatsu, Sotaro
AU - Nakagawa, Kazuhiko
N1 - Funding Information: Disclosure: Prof. K. Nishio reports receiving grants and personal fees from Otsuka Pharmaceutical Co., Ltd., Life Technologies Japan, Nippon Boehringer Ingelheim, and Eli Lilly Japan; grants from Ignyta , Inc., and Chugai Pharmaceutical Co., Ltd.; and personal fees from Eisai Co., Ltd., Pfizer, Novartis Pharma, Merck Sharp & Dohme, Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb, SymBio Pharmaceuticals, Solasia Pharma, Yakult Honsha, Roche Diagnostics, AstraZeneca, Sanofi, Guardant Health, Inc., Astellas Pharma, Inc., Takeda Pharmaceutical Co., Ltd., and Kobayashi Pharmaceutical, outside of the submitted work. Dr. Seto is an employee of Precision Medicine Asia and reports receiving lecture fees, honoraria, or other fees from AstraZeneca, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan, Merck Sharp & Dohme, Pfizer Japan, and Taiho Pharmaceutical, and grants from AbbVie Inc. , AstraZeneca , Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eli Lilly Japan K.K. , Kissei Pharmaceutical Co., Ltd. , LOXO Oncology, Inc., Merck Sharp & Dohme , Nippon Boehringer Ingelheim Co., Ltd. , Novartis , Pfizer Japan Inc. , and Takeda Pharmaceutical Company Limited. Dr. M. Nishio reports receiving grants and personal fees from Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb, Pfizer, Chugai Pharmaceutical Co., Ltd., Eli Lilly and Company, Taiho Pharmaceutical, AstraZeneca, Merck Sharp & Dohme, Novartis, Daiichi Sankyo, and Takeda Pharmaceutical Co., Ltd., and personal fees from Boehringer Ingelheim, Merck Biopharma, Teijin Pharma Limited, and AbbVie, outside of the submitted work. Prof. Dr. Reck reports receiving honoraria for lectures and consultancy from Amgen, Inc., AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly and Company, Merck, Mirati, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung, outside of the submitted work. Prof. Garon reports receiving grants from Eli Lilly and Company during the conduct of the study and, outside of the submitted work, grants from Novartis , AstraZeneca , Bristol-Myers Squibb Company , Dynavax, EMD Serono , Genentech , Inc., Iovance Biotherapeutics, Merck & Co., Inc. , Mirati, Neon, and Novartis . Dr. Sakai reports receiving personal fees from Roche Diagnostics , Bio-Rad , AstraZeneca , and Chugai Pharmaceutical Co., Ltd., outside of the submitted work. Dr. Goto reports receiving grants and personal fees from Chugai Pharmaceutical Co., Ltd. and Eli Lilly Japan K.K. during the conduct of the study and, outside of the submitted work, personal fees from Guardant Health, Inc. and Otsuka Pharmaceutical Co., Ltd., grants from Amgen Inc., Astellas Pharma Inc., Eisai Co., Ltd., Ignyta , Inc., Loxo Oncology, Inc., Medical & Biological Laboratories Co., Ltd., Merck Serono Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., and Sysmex Corporation, and grants and personal fees from Takeda Pharmaceutical Co., Ltd., Amgen Astellas BioPharma K.K., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol-Myers Squibb K.K., Daiichi Sankyo Co., Ltd., Janssen Pharmaceutical K.K., Kyowa Hakko Kirin Co., Ltd., Merck Biopharma Co., Ltd., Merck Sharp & Dohme K.K., Nippon Kayaku Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Pfizer, Inc., Taiho Pharmaceutical Co., Ltd., Thermo Fisher Scientific K.K., Xcoo, Inc., and Takeda Pharmaceutical Co., Ltd. Dr. Kato reports receiving grants and personal fees from AbbVie, Amgen Inc., AstraZeneca, Bristol-Myers Squibb, Chugai, Eli Lilly, Merck Biopharma, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical Co., Ltd., Pfizer, and Taiho; personal fees from Boehringer Ingelheim, Daiichi Sankyo, F. Hoffman-La Roche, Nippon Kayaku, Nitto Denko, Shionogi & Co., Sumitomo Dainippon, and Takeda Pharmaceutical Co., Ltd.; and grants from Astellas Pharma Inc. , Kyorin, Kyowa-Kirin, and Regeneron Pharmaceuticals Inc. , outside of the submitted work. Dr. Nakanishi reports receiving grants and personal fees from Chugai Pharmaceutical Co., Ltd. and personal fees from Eli Lilly and Company, AstraZeneca, Boehringer Ingelheim Japan, Merck Sharp & Dohme, Ono Pharmaceutical Co., Ltd., and Pfizer outside of the submitted work. Dr. Takahashi reports receiving grants from Japan Agency for Medical Research and Development during the conduct of the study and, outside of the submitted work, grants and personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd. , Merck Sharp & Dohme K.K., and Pfizer Japan Inc., and personal fees from Nippon Boehringer Ingelheim Co., Ltd. and Roche Diagnostics K.K. Dr. Yamamoto reports receiving grants and personal fees from Merck Sharp & Dohme K.K., AstraZeneca, Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Boehringer Ingelheim, Novartis, and Pfizer Inc.; personal fees from Thermo Fisher Scientific, Bristol-Myers Squibb, Life Technologies Japan Ltd., Nippon Kayaku, and Merck Biopharma; and grants from Astellas Pharma Inc. , Tsumura & Co., Shionogi & Co., Ltd., AbbVie G.K., Amgen Inc. , Kyorin Pharmaceutical Co., Ltd., Eisai Co., Ltd., Terumo Corporation , Toppan Printing Co., Ltd., and Tosoh outside of the submitted work. Prof. Kiura reports receiving personal fees from AstraZeneca K.K., Eli Lilly Japan K.K., and Novartis International AG; grants and personal fees from Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co. Ltd., Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme K.K., Chugai Pharmaceutical Co., Ltd., and Bristol-Myers Squibb K.K.; and grants from Teijin Pharma Limited, Shionogi & Co., Ltd., Nippon Kayaku Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., and Takeda Pharmaceutical Company Limited , outside of the submitted work. Dr. Ohe reports receiving grants and personal fees from Eli Lilly during the conduct of the study and, outside of the submitted work, grants and personal fees from AstraZeneca, Amgen Inc., Bristol-Myers Squibb, Chugai, Kyorin, Merck Sharp & Dohme, Nippon Kayaku, Ono Pharmaceutical Co., Ltd., Taiho, Takeda Pharmaceutical Co., Ltd., and Pfizer; personal fees from Boehringer Ingelheim, Celtrion, and Novartis; and grants from Janssen, Kissei Pharmaceutical Co., Ltd. , and Ignyta, Inc . Dr. Tamura reports receiving personal fees from Eli Lilly, Chugai, Ono Pharmaceutical Co., Ltd., Nippon Kayaku, Taiho Pharmaceutical, Boehringer Ingelheim, Merck Sharp & Dohme, and CMIC Shift Zero, outside of the submitted work. Dr. Visseren-Grul, Mrs. Frimodt-Moller, R. Hozak, Dr. Wijayawardana, Mrs. Zimmermann, Dr. Homma, and Dr. Enatsu are employees and minor shareholders of Eli Lilly and Company. Prof. Nakagawa reports receiving grants and personal fees from AstraZeneca K.K., Astellas Pharma Inc., Merck Sharp & Dohme K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., and Merck Serono Co., Ltd./Merck Biopharma Co., Ltd.; grants, personal fees, and other fees from Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., and Eli Lilly Japan K.K. during the conduct of the study and, outside of the submitted work, personal fees from Clinical Trial Co., Ltd., Medicus Shuppan, Publishers Co., Ltd., Care Net, Inc., Reno Medical K.K., Medical Review Co., Ltd., Roche Diagnostics K.K., Bayer Yakuhin, Ltd., Medical Mobile Communications Co., Ltd., 3H Clinical Trial Inc., Nichi-Iko Pharmaceutical Co., Ltd., Nanzando Co., Ltd., Yodosha Co., Ltd., Nikkei Business Publications, Inc., Thermo Fisher Scientific K.K., Yomiuri Telecasting Corporation, and Nippon Kayaku Co., Ltd.; personal fees and other fees from Kyorin Pharmaceutical Co., Ltd.; grants from inVentiv Health Japan, ICON Japan K.K., Gritsone Oncology Inc., Parexel International Corporation, Kissei Pharmaceutical Co., Ltd., EPS Corporation, Syneos Health, Pfizer R&D Japan G.K., A2 Healthcare Corporation, Quintiles Inc./IQVIA Services JAPAN K.K., EP-CRSU Co., Ltd., Linical Co., Ltd., Eisai Co., Ltd., CMIC Shift Zero K.K., Kyowa Hakko Kirin Co., Ltd., Bayer Yakuhin, Ltd., EPS International Co., Ltd., and Otsuka Pharmaceutical Co., Ltd.; grants and personal fees from Taiho Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., and AbbVie Inc.; and grants, personal fees, and other fees from Takeda Pharmaceutical Co., Ltd. Funding Information: This study was sponsored by Eli Lilly and Company , manufacturer and licensee of ramucirumab. Eli Lilly and Company was involved in the study design, data collection, data analysis, and preparation of the manuscript, and in the decision to submit the manuscript for publication. The authors thank all the study participants. Medical writing assistance was provided by Rebecca Lew, PhD, CMPP, and Prudence Stanford, PhD, of ProScribe—Envision Pharma Group, and was funded by Eli Lilly and Company . ProScribe’s services complied with international guidelines for Good Publication Practice (GPP3). Funding Information: Disclosure: Prof. K. Nishio reports receiving grants and personal fees from Otsuka Pharmaceutical Co., Ltd., Life Technologies Japan, Nippon Boehringer Ingelheim, and Eli Lilly Japan; grants from Ignyta, Inc., and Chugai Pharmaceutical Co., Ltd.; and personal fees from Eisai Co., Ltd., Pfizer, Novartis Pharma, Merck Sharp & Dohme, Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb, SymBio Pharmaceuticals, Solasia Pharma, Yakult Honsha, Roche Diagnostics, AstraZeneca, Sanofi, Guardant Health, Inc., Astellas Pharma, Inc., Takeda Pharmaceutical Co., Ltd., and Kobayashi Pharmaceutical, outside of the submitted work. Dr. Seto is an employee of Precision Medicine Asia and reports receiving lecture fees, honoraria, or other fees from AstraZeneca, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan, Merck Sharp & Dohme, Pfizer Japan, and Taiho Pharmaceutical, and grants from AbbVie Inc., AstraZeneca, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., LOXO Oncology, Inc., Merck Sharp & Dohme, Nippon Boehringer Ingelheim Co., Ltd., Novartis, Pfizer Japan Inc., and Takeda Pharmaceutical Company Limited. Dr. M. Nishio reports receiving grants and personal fees from Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb, Pfizer, Chugai Pharmaceutical Co., Ltd., Eli Lilly and Company, Taiho Pharmaceutical, AstraZeneca, Merck Sharp & Dohme, Novartis, Daiichi Sankyo, and Takeda Pharmaceutical Co., Ltd., and personal fees from Boehringer Ingelheim, Merck Biopharma, Teijin Pharma Limited, and AbbVie, outside of the submitted work. Prof. Dr. Reck reports receiving honoraria for lectures and consultancy from Amgen, Inc., AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly and Company, Merck, Mirati, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung, outside of the submitted work. Prof. Garon reports receiving grants from Eli Lilly and Company during the conduct of the study and, outside of the submitted work, grants from Novartis, AstraZeneca, Bristol-Myers Squibb Company, Dynavax, EMD Serono, Genentech, Inc., Iovance Biotherapeutics, Merck & Co., Inc., Mirati, Neon, and Novartis. Dr. Sakai reports receiving personal fees from Roche Diagnostics, Bio-Rad, AstraZeneca, and Chugai Pharmaceutical Co., Ltd., outside of the submitted work. Dr. Goto reports receiving grants and personal fees from Chugai Pharmaceutical Co., Ltd. and Eli Lilly Japan K.K. during the conduct of the study and, outside of the submitted work, personal fees from Guardant Health, Inc. and Otsuka Pharmaceutical Co., Ltd., grants from Amgen Inc., Astellas Pharma Inc., Eisai Co., Ltd., Ignyta, Inc., Loxo Oncology, Inc., Medical & Biological Laboratories Co., Ltd., Merck Serono Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., and Sysmex Corporation, and grants and personal fees from Takeda Pharmaceutical Co., Ltd., Amgen Astellas BioPharma K.K., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol-Myers Squibb K.K., Daiichi Sankyo Co., Ltd., Janssen Pharmaceutical K.K., Kyowa Hakko Kirin Co., Ltd., Merck Biopharma Co., Ltd., Merck Sharp & Dohme K.K., Nippon Kayaku Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Pfizer, Inc., Taiho Pharmaceutical Co., Ltd., Thermo Fisher Scientific K.K., Xcoo, Inc., and Takeda Pharmaceutical Co., Ltd. Dr. Kato reports receiving grants and personal fees from AbbVie, Amgen Inc., AstraZeneca, Bristol-Myers Squibb, Chugai, Eli Lilly, Merck Biopharma, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical Co., Ltd., Pfizer, and Taiho; personal fees from Boehringer Ingelheim, Daiichi Sankyo, F. Hoffman-La Roche, Nippon Kayaku, Nitto Denko, Shionogi & Co., Sumitomo Dainippon, and Takeda Pharmaceutical Co., Ltd.; and grants from Astellas Pharma Inc., Kyorin, Kyowa-Kirin, and Regeneron Pharmaceuticals Inc., outside of the submitted work. Dr. Nakanishi reports receiving grants and personal fees from Chugai Pharmaceutical Co., Ltd. and personal fees from Eli Lilly and Company, AstraZeneca, Boehringer Ingelheim Japan, Merck Sharp & Dohme, Ono Pharmaceutical Co., Ltd., and Pfizer outside of the submitted work. Dr. Takahashi reports receiving grants from Japan Agency for Medical Research and Development during the conduct of the study and, outside of the submitted work, grants and personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme K.K., and Pfizer Japan Inc., and personal fees from Nippon Boehringer Ingelheim Co., Ltd. and Roche Diagnostics K.K. Dr. Yamamoto reports receiving grants and personal fees from Merck Sharp & Dohme K.K., AstraZeneca, Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Boehringer Ingelheim, Novartis, and Pfizer Inc.; personal fees from Thermo Fisher Scientific, Bristol-Myers Squibb, Life Technologies Japan Ltd., Nippon Kayaku, and Merck Biopharma; and grants from Astellas Pharma Inc., Tsumura & Co., Shionogi & Co., Ltd., AbbVie G.K., Amgen Inc., Kyorin Pharmaceutical Co., Ltd., Eisai Co., Ltd., Terumo Corporation, Toppan Printing Co., Ltd., and Tosoh outside of the submitted work. Prof. Kiura reports receiving personal fees from AstraZeneca K.K., Eli Lilly Japan K.K., and Novartis International AG; grants and personal fees from Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co. Ltd., Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme K.K., Chugai Pharmaceutical Co., Ltd., and Bristol-Myers Squibb K.K.; and grants from Teijin Pharma Limited, Shionogi & Co., Ltd., Nippon Kayaku Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., and Takeda Pharmaceutical Company Limited, outside of the submitted work. Dr. Ohe reports receiving grants and personal fees from Eli Lilly during the conduct of the study and, outside of the submitted work, grants and personal fees from AstraZeneca, Amgen Inc., Bristol-Myers Squibb, Chugai, Kyorin, Merck Sharp & Dohme, Nippon Kayaku, Ono Pharmaceutical Co., Ltd., Taiho, Takeda Pharmaceutical Co., Ltd., and Pfizer; personal fees from Boehringer Ingelheim, Celtrion, and Novartis; and grants from Janssen, Kissei Pharmaceutical Co., Ltd., and Ignyta, Inc. Dr. Tamura reports receiving personal fees from Eli Lilly, Chugai, Ono Pharmaceutical Co., Ltd., Nippon Kayaku, Taiho Pharmaceutical, Boehringer Ingelheim, Merck Sharp & Dohme, and CMIC Shift Zero, outside of the submitted work. Dr. Visseren-Grul, Mrs. Frimodt-Moller, R. Hozak, Dr. Wijayawardana, Mrs. Zimmermann, Dr. Homma, and Dr. Enatsu are employees and minor shareholders of Eli Lilly and Company. Prof. Nakagawa reports receiving grants and personal fees from AstraZeneca K.K., Astellas Pharma Inc., Merck Sharp & Dohme K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., and Merck Serono Co., Ltd./Merck Biopharma Co., Ltd.; grants, personal fees, and other fees from Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., and Eli Lilly Japan K.K. during the conduct of the study and, outside of the submitted work, personal fees from Clinical Trial Co., Ltd., Medicus Shuppan, Publishers Co., Ltd., Care Net, Inc., Reno Medical K.K., Medical Review Co., Ltd., Roche Diagnostics K.K., Bayer Yakuhin, Ltd., Medical Mobile Communications Co., Ltd., 3H Clinical Trial Inc., Nichi-Iko Pharmaceutical Co., Ltd., Nanzando Co., Ltd., Yodosha Co., Ltd., Nikkei Business Publications, Inc., Thermo Fisher Scientific K.K., Yomiuri Telecasting Corporation, and Nippon Kayaku Co., Ltd.; personal fees and other fees from Kyorin Pharmaceutical Co., Ltd.; grants from inVentiv Health Japan, ICON Japan K.K., Gritsone Oncology Inc., Parexel International Corporation, Kissei Pharmaceutical Co., Ltd., EPS Corporation, Syneos Health, Pfizer R&D Japan G.K., A2 Healthcare Corporation, Quintiles Inc./IQVIA Services JAPAN K.K., EP-CRSU Co., Ltd., Linical Co., Ltd., Eisai Co., Ltd., CMIC Shift Zero K.K., Kyowa Hakko Kirin Co., Ltd., Bayer Yakuhin, Ltd., EPS International Co., Ltd., and Otsuka Pharmaceutical Co., Ltd.; grants and personal fees from Taiho Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., and AbbVie Inc.; and grants, personal fees, and other fees from Takeda Pharmaceutical Co., Ltd.This study was sponsored by Eli Lilly and Company, manufacturer and licensee of ramucirumab. Eli Lilly and Company was involved in the study design, data collection, data analysis, and preparation of the manuscript, and in the decision to submit the manuscript for publication. The authors thank all the study participants. Medical writing assistance was provided by Rebecca Lew, PhD, CMPP, and Prudence Stanford, PhD, of ProScribe?Envision Pharma Group, and was funded by Eli Lilly and Company. ProScribe's services complied with international guidelines for Good Publication Practice (GPP3). Eli Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the US and EU and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, and blank or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org. Publisher Copyright: © 2021 The Authors
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - Circulating tumor DNA
KW - EGFR
KW - Japan
KW - Non–small cell lung cancer
KW - Ramucirumab
UR - http://www.scopus.com/inward/record.url?scp=85122680134&partnerID=8YFLogxK
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U2 - 10.1016/j.jtocrr.2021.100171
DO - 10.1016/j.jtocrr.2021.100171
M3 - Article
AN - SCOPUS:85122680134
VL - 2
JO - JTO Clinical and Research Reports
JF - JTO Clinical and Research Reports
SN - 2666-3643
IS - 6
M1 - 100171
ER -