Abstract
Introduction: Osimertinib is a standard first-line treatment for non–small cell lung cancer (NSCLC) harboring mutations of the epidermal growth factor receptor gene (EGFR). However, tumors with the L858R mutation appear to be less sensitive to EGFR–tyrosine kinase inhibitors (TKIs) than those with exon-19 deletions, and subgroup analysis of the FLAURA study revealed that osimertinib did not significantly prolong overall survival (OS) compared with gefitinib or erlotinib in patients with the L858R. The RELAY study revealed a similar high efficacy of combination therapy with erlotinib plus ramucirumab (E+RAM) in patients with L858R and in those with exon-19 deletions. Patients who acquire the TKI resistance–associated T790M mutation during E+RAM treatment can also expect to receive benefit from second-line osimertinib. We have therefore planned a phase III study to evaluate the clinical efficacy of E+RAM compared with osimertinib monotherapy for untreated patients with advanced NSCLC harboring L858R. Patients and Methods: A total of 230 patients will be enrolled. The primary end point is time to failure of strategy (TFS), which is defined for this study as the time from randomization of treatment until disease progression or death on osimertinib, or the time from randomization until first disease progression or death of the primary treatment when osimertinib is not administered in the E+RAM group. Secondary end points include OS and progression-free survival. Conclusion: This is the first phase III clinical trial to target only NSCLC patients with the L858R mutation. Its results may establish an optimal treatment for such individuals.
Original language | English |
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Pages (from-to) | e257-e263 |
Journal | Clinical Lung Cancer |
Volume | 23 |
Issue number | 3 |
DOIs | |
Publication status | Published - May 2022 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Oncology
- Pulmonary and Respiratory Medicine
- Cancer Research
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Phase III Clinical Trial for the Combination of Erlotinib Plus Ramucirumab Compared With Osimertinib in Previously Untreated Advanced or Recurrent Non–Small Cell Lung Cancer Positive for the L858R Mutation of EGFR : REVOL858R (WJOG14420L). / Haratake, Naoki; Hayashi, Hidetoshi; Shimokawa, Mototsugu et al.
In: Clinical Lung Cancer, Vol. 23, No. 3, 05.2022, p. e257-e263.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Phase III Clinical Trial for the Combination of Erlotinib Plus Ramucirumab Compared With Osimertinib in Previously Untreated Advanced or Recurrent Non–Small Cell Lung Cancer Positive for the L858R Mutation of EGFR
T2 - REVOL858R (WJOG14420L)
AU - Haratake, Naoki
AU - Hayashi, Hidetoshi
AU - Shimokawa, Mototsugu
AU - Nakano, Yusuke
AU - Azuma, Koichi
AU - Oki, Masahide
AU - Ota, Keiichi
AU - Yoshioka, Hiroshige
AU - Sakamoto, Tomohiro
AU - Yamamoto, Nobuyuki
AU - Nakagawa, Kazuhiko
AU - Seto, Takashi
N1 - Funding Information: The study is funded by Eli Lilly Japan K.K. This study will be conducted with support from the West Japan Oncology Group (WJOG) Data Center (Osaka, Japan), and the authors thank the data managers and other support staff of WJOG for their contributions. Funding Information: Naoki Haratake reports personal fees from Eli Lilly Japan K.K., personal fees from AstraZeneca, personal fees from Chugai Pharmaceutical Co Ltd, outside the submitted work. Hidetoshi Hayashi reports grants and personal fees from AstraZeneca K.K, grants and personal fees from Boehringer Ingelheim Japan Inc, grants and personal fees from Bristol-Myers Squibb Co Ltd, grants and personal fees from Chugai Pharmaceutical Co Ltd, grants and personal fees from Eli Lilly Japan K.K., personal fees from Kyorin pharmaceutical co ltd, grants and personal fees from Merck Biopharma Co, Ltd, personal fees from MSD K.K., personal fees from Novartis pharmaceuticals k.k, personal fees from Ono Pharmaceutical Co Ltd, personal fees from Shanghai Haihe Biopharm, grants and personal fees from Taiho Pharmaceutical Co Ltd, grants and personal fees from Takeda Pharmaceutical Co Ltd, personal fees from Pfizer Japan Inc, personal fees from Merck Biopharma Co, Ltd, grants from Nippon Boehringer Ingelheim Co,Ltd, from Daiichi Sankyo Co, Ltd, grants from SymBio Pharmaceuticals Limited, grants from AbbVie Inc, grants from inVentiv Health Japan, grants from ICON Japan K.K, grants from GRITSONE ONCOLOGY.INC, grants from PAREXEL International Corp., grants from Kissei Pharmaceutical Co,Ltd, grants from EPS Corporation, grants from Syneos Health, grants from Pfizer R&D Japan G.K, grants from A2 Healthcare Corp., grants from Quintiles Inc, grants from IQVIA Services JAPAN K.K, grants from EP-CRSU CO, LTD, grants from Linical Co,Ltd, grants from Eisai Co, Ltd, grants from CMIC Shift Zero K.K., grants from Kyowa Hakko Kirin Co,Ltd, grants from Bayer Yakuhin, Ltd, grants from EPS International Co, Ltd, grants from Otsuka Pharmaceutical Co, Ltd, outside the submitted work. Koichi Azuma reports personal fees from AstraZeneca K.K., personal fees from Chugai Pharmaceutical Co Ltd, personal fees from Bristol-Myers Squibb Co Ltd, personal fees from Ono Pharmaceutical Co Ltd, personal fees from MSD K.K., outside the submitted work. Masahide Oki reports personal fees from AstraZeneca K.K., from null, outside the submitted work. Hiroshige Yoshioka reports personal fees from Chugai Pharmaceutical Co Ltd, personal fees from Eli Lilly Japan K.K., personal fees from AstraZeneca K.K, personal fees from Boehringer Ingelheim Japan Inc, personal fees from Pfizer Japan Inc, during the conduct of the study; personal fees from TAIHO PHARMACEUTICAL CO, LTD, personal fees from MSD K.K., personal fees from Delta Fly Pharma, personal fees from Nippon Kayaku, personal fees from Novartis pharmaceuticals k.k, personal fees from Otsuka Pharmaceutical Co, Ltd, outside the submitted work. Tomohiro Sakamoto reports personal fees from AstraZeneca K.K., personal fees from Chugai Pharmaceutical Co, Ltd, personal fees from Kyowa Kirin Co, Ltd, personal fees from Merck KGaA, personal fees from Eli Lilly Japan K.K., personal fees from Novartis Pharma K.K., personal fees from Nippon Boehringer Ingelheim Co, Ltd, personal fees from ONO PHARMACEUTICAL CO, LTD, personal fees from MSD K.K., personal fees from Illumina K.K., outside the submitted work. Nobuyuki Yamamoto reports personal fees from AstraZeneca, personal fees from MSD K.K., personal fees from ONO PHARMACEUTICAL CO, LTD, personal fees from Thermo Fisher Scientific, personal fees from DAIICHI SANKYO CO, grants and personal fees from TAIHO PHARMACEUTICAL CO, LTD, personal fees from Takeda Pharmaceutical CO, LTD, grants and personal fees from Chugai Pharmaceutical CO, LTD, personal fees from Eli Lilly Japan K.K., grants and personal fees from Boehringer-Ingelheim, personal fees from Novartis, personal fees from Pfizer Inc, personal fees from Bristol-Myers Squibb, personal fees from NIPPON KAYAKU, personal fees from GlaxoSmithKline K.K., personal fees from Sanofi K.K., personal fees from Hisamitsu Pharmaceutical CoInc, personal fees from Merk biopharma, grants from Tosoh Life Science Research Laboratory, outside the submitted work. Kazuhiko Nakagawa reports grants and personal fees from AstraZeneca K.K., grants and personal fees from Astellas Pharma Inc, grants and personal fees from MSD K.K., grants, personal fees and other from Ono Pharmaceutical Co,Ltd, grants and personal fees from Nippon Boehringer Ingelheim Co,Ltd, grants and personal fees from Novartis Pharma K.K., grants, personal fees and other from Pfizer Japan Inc, grants and personal fees from Bristol Myers Squibb Company, grants, personal fees and other from Eli Lilly Japan K.K., grants and personal fees from Chugai Pharmaceutical Co,Ltd, grants and personal fees from Daiichi Sankyo Co, Ltd, grants and personal fees from Merck Serono Co, Ltd/ Merck Biopharma Co, Ltd, during the conduct of the study; personal fees from Clinical Trial Co, Ltd, personal fees from MEDICUS SHUPPAN,Publishers Co, Ltd, personal fees from Care Net, Inc, personal fees from Reno. Medical K.K., personal fees and other from KYORIN Pharmaceutical Co,Ltd, personal fees from Medical Review Co, Ltd, personal fees from Roche Diagnostics K.K., personal fees from Bayer Yakuhin, Ltd, personal fees from Medical Mobile Communications co, Ltd, personal fees from 3H Clinical Trial Inc, personal fees from Nichi-Iko Pharmaceutical Co, Ltd, grants, personal fees and other from Takeda Pharmaceutical Co,Ltd, grants and personal fees from Taiho Pharmaceutical Co,Ltd, grants and personal fees from SymBio Pharmaceuticals Limited., personal fees from NANZANDO Co,Ltd, personal fees from YODOSHA CO, LTD, personal fees from Nikkei Business Publications, Inc, personal fees from Thermo Fisher Scientific K.K., personal fees from YOMIURI TELECASTING CORPORATION., personal fees from Nippon Kayaku Co,Ltd, grants and personal fees from AbbVie Inc, grants from inVentiv Health Japan, grants from ICON Japan K.K., grants from GRITSONE ONCOLOGY.INC, grants from PAREXEL International Corp., grants from Kissei Pharmaceutical Co,Ltd, grants from EPS Corporation., grants from Syneos Health., grants from Pfizer R&D Japan G.K., grants from A2 Healthcare Corp., grants from Quintiles Inc / IQVIA Services JAPAN K.K., grants from EP-CRSU CO, LTD, grants from Linical Co,Ltd, grants from Eisai Co, Ltd, grants from CMIC Shift Zero K.K., grants from Kyowa Hakko Kirin Co,Ltd, grants from Bayer Yakuhin, Ltd, grants from EPS International Co, Ltd, grants from Otsuka Pharmaceutical Co, Ltd, outside the submitted work. Takashi Seto has received grants and honoraria from Chugai Pharm aceutical, grants and honoraria from Daiichi Sankyo, grants and honoraria from Eli Lilly Japan, grants and honoraria from MSD, grants and honoraria from Novartis Pharma, grants and honoraria from Pfizer Japan, grants and honoraria from Takeda Pharmaceutical, grants from Abbvie, grants from Kissei Pharmaceutical, grants from LOXO Oncology, grants from Merck Biopharma, honoraria from AstraZeneca, honoraria from Bristol-Myers Squibb, honoraria from Covidien Japan, honoraria from Kyowa Hakko Kirin, honoraria from Mochida Pharmaceutical, honoraria from Nippon Boehringer Ingelheim, honoraria from Ono Pharmaceutical, honoraria from Taiho Pharmaceutical, honoraria from Thermo Fisher Scientific, honoraria from Precision Medicine Asia. The other authors have stated that they have no conflict of interest. Funding Information: The study is funded by Eli Lilly Japan K .K. This study will be conducted with support from the West Japan Oncology Group (WJOG) Data Center (Osaka, Japan), and the authors thank the data managers and other support staff of WJOG for their contributions. Publisher Copyright: © 2021
PY - 2022/5
Y1 - 2022/5
N2 - Introduction: Osimertinib is a standard first-line treatment for non–small cell lung cancer (NSCLC) harboring mutations of the epidermal growth factor receptor gene (EGFR). However, tumors with the L858R mutation appear to be less sensitive to EGFR–tyrosine kinase inhibitors (TKIs) than those with exon-19 deletions, and subgroup analysis of the FLAURA study revealed that osimertinib did not significantly prolong overall survival (OS) compared with gefitinib or erlotinib in patients with the L858R. The RELAY study revealed a similar high efficacy of combination therapy with erlotinib plus ramucirumab (E+RAM) in patients with L858R and in those with exon-19 deletions. Patients who acquire the TKI resistance–associated T790M mutation during E+RAM treatment can also expect to receive benefit from second-line osimertinib. We have therefore planned a phase III study to evaluate the clinical efficacy of E+RAM compared with osimertinib monotherapy for untreated patients with advanced NSCLC harboring L858R. Patients and Methods: A total of 230 patients will be enrolled. The primary end point is time to failure of strategy (TFS), which is defined for this study as the time from randomization of treatment until disease progression or death on osimertinib, or the time from randomization until first disease progression or death of the primary treatment when osimertinib is not administered in the E+RAM group. Secondary end points include OS and progression-free survival. Conclusion: This is the first phase III clinical trial to target only NSCLC patients with the L858R mutation. Its results may establish an optimal treatment for such individuals.
AB - Introduction: Osimertinib is a standard first-line treatment for non–small cell lung cancer (NSCLC) harboring mutations of the epidermal growth factor receptor gene (EGFR). However, tumors with the L858R mutation appear to be less sensitive to EGFR–tyrosine kinase inhibitors (TKIs) than those with exon-19 deletions, and subgroup analysis of the FLAURA study revealed that osimertinib did not significantly prolong overall survival (OS) compared with gefitinib or erlotinib in patients with the L858R. The RELAY study revealed a similar high efficacy of combination therapy with erlotinib plus ramucirumab (E+RAM) in patients with L858R and in those with exon-19 deletions. Patients who acquire the TKI resistance–associated T790M mutation during E+RAM treatment can also expect to receive benefit from second-line osimertinib. We have therefore planned a phase III study to evaluate the clinical efficacy of E+RAM compared with osimertinib monotherapy for untreated patients with advanced NSCLC harboring L858R. Patients and Methods: A total of 230 patients will be enrolled. The primary end point is time to failure of strategy (TFS), which is defined for this study as the time from randomization of treatment until disease progression or death on osimertinib, or the time from randomization until first disease progression or death of the primary treatment when osimertinib is not administered in the E+RAM group. Secondary end points include OS and progression-free survival. Conclusion: This is the first phase III clinical trial to target only NSCLC patients with the L858R mutation. Its results may establish an optimal treatment for such individuals.
UR - http://www.scopus.com/inward/record.url?scp=85120802793&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85120802793&partnerID=8YFLogxK
U2 - 10.1016/j.cllc.2021.10.007
DO - 10.1016/j.cllc.2021.10.007
M3 - Article
AN - SCOPUS:85120802793
VL - 23
SP - e257-e263
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
SN - 1525-7304
IS - 3
ER -