Afatinib plus bevacizumab combination after osimertinib resistance in advanced EGFR-mutant non-small cell lung cancer: Phase II ABCD-study.

Autor: Hata A; Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center, Japan. Electronic address: akitohata@hotmail.com., Katakami N; Department of Medical Oncology, Takarazuka City Hospital, Japan., Takase N; Department of Medical Oncology, Takarazuka City Hospital, Japan., Kibata K; Department of Respiratory Medicine, First Department of Internal Medicine, Kansai Medical University, Japan., Yamanaka Y; Department of Respiratory Medicine, First Department of Internal Medicine, Kansai Medical University, Japan., Tamiya M; Department of Thoracic Oncology, Osaka International Cancer Institute, Japan., Mori M; Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, Japan., Kijima T; Department of Respiratory Medicine and Hematology, Hyogo Medical University, Japan., Morita S; Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Japan., Sakai K; Department of Genome Biology, Kindai University, Faculty of Medicine, Japan., Nishio K; Department of Genome Biology, Kindai University, Faculty of Medicine, Japan.
Jazyk: angličtina
Zdroj: Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2024 Nov; Vol. 197, pp. 107988. Date of Electronic Publication: 2024 Oct 05.
DOI: 10.1016/j.lungcan.2024.107988
Abstrakt: Introduction: Many clinical studies showed a synergy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and vascular endothelial growth factor inhibitors. We hypothesized afatinib plus bevacizumab exerts clinical potency after developing various osimertinib resistant mechanisms.
Methods: EGFR-mutant non-small cell lung cancer patients were enrolled after osimertinib resistance. Afatinib at 30-40 mg/day and bevacizumab at 15 mg/kg tri-weekly were administered until progression. Plasma/histologic rebiopsied samples after osimertinib failure were analyzed to examine resistant mechanisms: gene alterations/copy-number gain using cancer personalized profiling by deep sequencing.
Results: Between January 2018 and October 2020, 28 patients were enrolled. Response and disease control rates were 17.9 % and 78.6 %, respectively. Median duration of response was 9.0 (range, 4.2-22.3) months. Median progression-free and overall survivals were 2.7 and 9.3 months, respectively. Twenty-eight (100 %) plasma and/or 21 (75 %) histologic rebiopsies identified: 17 (61 %) TP53; 15 (54 %) T790M; 9 (32 %) uncommon EGFR; 9 (32 %) MET; 6 (21 %) C797S; 3 (11 %) BRAF; 2 (7 %) HER2; 2 (7 %) KRAS; and 2 (7 %) PI3K mutations. One (17 %) of 6 C797S patients showed complete response. Three (33 %) of 9 uncommon EGFR-mutated patients achieved radiographic response. Neither 15 T790M-positive nor 6 EGFR downstream signaling mutations: BRAF; KRAS; or PI3K-positive patients responded, but 5 (38 %) of 13 T790M-negative patients responded. Adverse events ≥ grade 3 and incidence ≥ 5 % were: hypertension (29 %); proteinuria (7 %); and diarrhea (7 %). There were neither treatment-related death nor interstitial lung disease.
Conclusions: Selected population could obtain clinical benefit from afatinib plus bevacizumab, based on rebiopsy results after osimertinib resistance.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Akito Hata: grants from MSD, Eli Lilly, Chugai, Taiho, Boehringer Ingelheim, AstraZeneca, AbbVie, and personal fees from AstraZenaca, Eli Lilly, MSD, Chugai, Pfizer, Boehringer Ingelheim, Taiho. Nobuyuki Katakami: grants from MSD, Ono, Delta-Fly, AstraZeneca, AbbVie, Chugai, and personal fees from Ono, Chugai, Pfizer, AstraZeneca, Boehringer Ingelheim, Taiho, MSD, Novartis, Bristol-Myers Squibb, Takeda, GlaxoSmithKline. Naoto Takase: personal fees from Taiho, Eisai, Merck, MSD, AstraZeneca, Nippon Kayaku, Eli Lilly, Ono, Bristol-Myers Squibb, Eisai, Daiichi-Sankyo, Boehringer Ingelheim, Chugai, Takeda, and Kyorin. Motohiro Tamiya: grants from Boehringer Ingelheim, MSD, Eisai, Janssen, Ono, Daiichi-Sankyo, Chugai, and personal fees from Boehringer Ingelheim, AstraZeneca, Eli Lilly, Asahikasei, Bristol-Myers Squibb, Amgen, Daiichi-Sankyo, Chugai, Taiho, Pfizer Ono, MSD, Kyowa-Kirin. Masahide Mori: grants from Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Delta-fly, MSD, Janssen, Ono, and personal fees from Astrazeneca, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eli Lilly, Kyowa-kirin, MSD, Nippon Kayaku, Novaritis, Ono, Otsuka, Pfizer, Shionogi, Taiho, Takeda. Takashi Kijima: grants from Chugai, Taiho, GlaxoSmithKline, and personal fees from Chugai, AstraZeneca, Ono, Bristol-Myers Squibb, and GlaxoSmithKline. Satoshi Morita: personal fees from AstraZeneca, Bristol-Myers Squibb, Chugai, Eli Lilly, MSD, Pfizer, and Boehringer Ingelheim. Kazuko Sakai: personal fees from Hitachi, Life Technologies, Chugai, Takeda, and Qiagen. Kazuto Nishio: grants from Boehringer Ingelheim, West Japan Oncology Group, Clinical Research Support Center Kyushu, Nichirei Biosciences, Eli Lilly, Hitachi, Sysmex, Otsuka, consulting fees from SymBio, Solasia, Eli Lilly, Otsuka, and personal fees from Chugai, Pfizer, Eli Lilly, MSD, Novartis, AstraZeneca, Amgen, Merck, Roche Diagnostics, Yakult, Guardant Health, Takeda, Boehringer Ingelheim, Fujirebio, Bristol-Myers Squibb, Merck, Janssen, Daiichi-Sankyo, Ono. All other authors declare no conflicts of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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