TY - JOUR
T1 - A phase II trial of EGFR-TKI readministration with afatinib in advanced non-small-cell lung cancer harboring a sensitive non-T790M EGFR mutation
T2 - Okayama Lung Cancer Study Group trial 1403
AU - Oda, Naohiro
AU - Hotta, Kastuyuki
AU - Ninomiya, Kiichiro
AU - Minami, Daisuke
AU - Ichihara, Eiki
AU - Murakami, Toshi
AU - Yokoyama, Toshihide
AU - Ichikawa, Hirohisa
AU - Chikamori, Kenichi
AU - Takigawa, Nagio
AU - Ochi, Nobuaki
AU - Harita, Shingo
AU - Maeda, Yoshinobu
AU - Kiura, Katsuyuki
N1 - Funding Information:
Conflict of interest NO has received grants from Boehringer-Ingel-heim, during the conduct of the study. KH has received grants and personal fees from Boehringer-Ingelheim, during the conduct of the study; grants and personal fees from AstraZeneca, grants and personal fees from Ono Pharmaceutical, personal fees from Nihon Kayaku, personal fees from Taiho Pharmaceutical, grants and personal fees from Chugai Pharmaceutical, personal fees from Astellas, grants and personal fees from Novartis, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from Eli Lilly Japan, grants and personal fees from Merck Sharp Dohme, outside the submitted work. KN has received grants from Boehringer-Ingelheim, during the conduct of the study; personal fees from Bristol-Myers Squibb, other from Astra-Zeneca, personal fees from Ono Pharmaceutical, outside the submitted work. EI has received grants from Boehringer-Ingelheim, during the conduct of the study; personal fees from AstraZeneca, personal fees from Ono Pharmaceutical, grants and personal fees from Merck Sharp Dohme, personal fees from Chugai Pharmaceutical, personal fees from Novartis, personal fees from Bristol-Myers Squibb, grants from Eli Lilly Japan, outside the submitted work. TY has received personal fees from AstraZeneca, personal fees from Ono Pharmaceutical, personal fees from Taiho Pharmaceutical, personal fees from Eli Lilly Japan, outside the submitted work. KC has received grants and personal fees from Chugai pharmaceutical, grants from Bristol-Myers Squibb, personal fees from Eli Lilly Japan, grants from Taiho Pharmaceutical, personal fees from Ono Pharmaceutical, outside the submitted work;. NT has received grants and personal fees from Eli Lilly Japan, grants and personal fees from AstraZeneca, grants and personal fees from Daiichi-Sankyo Pharmaceutical, grants and personal fees from Chugai Pharmaceutical, grants and personal fees from Taiho Pharmaceutical, grants and personal fees from Pfizer Inc. Japan, grants and personal fees from Boehringer-Ingelheim, grants and personal fees from Ono Pharmaceutical, grants and personal fees from Kyowa Hakko Kirin, grants from Nippon Kayaku, grants from Takeda Pharmaceutical, personal fees from Merck Sharp Dohme, personal fees from Novartis, outside the submitted work. YM has received grants from Bristol-Myers Squibb, Pfizer, Otsuka Pharmaceutical, Kyowa Hakko Kirin, Merck Sharp Dohme, Eisai, Mochida Pharmaceutical, Ono Pharmaceutical,
Funding Information:
Acknowledgements The authors wish to acknowledge and thank the coordinators and all the other investigators who contributed to this study; independent data-monitoring committee members (Mikio Kata-oka and Masafumi Fujii) and site investigators (Hiroshige Yoshioka [Kurashiki Central Hospital], Masayuki Yasugi [Chugoku Central Hospital], Daijiro Harada [Shikoku Cancer Center], Shoichi Kuyama, Ken-ichiro Kudo [Iwakuni Medical Center], Koji Inoue, Tomonori Moritaka [Ehime Prefectural Central Hospital], Masaaki Inoue [Shimonoseki City Hospital], Takuo Shibayama [Okayama Medical Center], Daizo Kishino, Etsuko Kurimoto [Himeji Red Cross Hospital], and Takashi Ninomiya, Toshio Kubo, Kadoaki Ohashi, Go Makimoto, Satoru Senoo, Kazuya Nishii, Hiromi Watanabe, Chihiro Ando, Masahiro Tabata, Taizo Hirata, Hisao Higo [Okayama University Hospital]). The study received support from the Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan. The study received no specific grant from any profit fundings.
Funding Information:
Astellas, Meiji Seika Pharma, Asahi Kasei Pharma., Nippon Shinyaku, Toyama Chemical., and Yakult Honsha, outside the submitted work. KK has received from personal fees from Nippon Boehringer-Ingel-heim, during the conduct of the study; grants from Chugai Pharmaceutical, grants from Pfizer, grants from Novartis, grants and personal fees from Taiho pharmaceutical, grants from Eli Lilly Japan, grants and personal fees from Ono Pharmaceutical, personal fees from Astra-Zeneca, personal fees from Nippon Kayaku, personal fees from Daiichi Sankyo, personal fees from Shionogi, outside the submitted work. All other authors declare that they have no conflict of interest.
Funding Information:
The authors wish to acknowledge and thank the coordinators and all the other investigators who contributed to this study; independent data-monitoring committee members (Mikio Kataoka and Masafumi Fujii) and site investigators (Hiroshige Yoshioka [Kurashiki Central Hospital], Masayuki Yasugi [Chugoku Central Hospital], Daijiro Harada [Shikoku Cancer Center], Shoichi Kuyama, Kenichiro Kudo [Iwakuni Medical Center], Koji Inoue, Tomonori Moritaka [Ehime Prefectural Central Hospital], Masaaki Inoue [Shimonoseki City Hospital], Takuo Shibayama [Okayama Medical Center], Daizo Kishino, Etsuko Kurimoto [Himeji Red Cross Hospital], and Takashi Ninomiya, Toshio Kubo, Kadoaki Ohashi, Go Makimoto, Satoru Senoo, Kazuya Nishii, Hiromi Watanabe, Chihiro Ando, Masahiro Tabata, Taizo Hirata, Hisao Higo [Okayama University Hospital]). The study received support from the Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan. The study received no specific grant from any profit fundings.
Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Purpose: The aim of this study was to evaluate the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) readministration using afatinib in patients with non-small-cell lung cancer (NSCLC) with a sensitive non-T790M EGFR mutation who had received cytotoxic chemotherapy after acquiring resistance to EGFR-TKIs. Methods: Eligible patients had EGFR-mutant tumors resistant to first- or second-generation EGFR-TKIs and an EGFR-TKI-free period with cytotoxic agents. Confirmation of absence of the T790M mutation was required before registration. Afatinib (40 mg/body) was administered daily. The primary endpoint was progression-free survival (PFS). We assumed estimated and threshold PFS times of 3.3 and 1 months, with an α of 0.05 and β of 0.1, respectively. Results: Twelve patients were enrolled from December 2014 to May 2017. The objective response rate and disease control rate were 17% and 84%, respectively. The median PFS time was 4.2 months (95% confidence interval [CI] 2.0–5.8), which met the pre-defined primary endpoint. The median overall survival was 11.6 months (95% CI 9.2-not reached). Grade 3 or worse adverse events included diarrhea (25%), elevated creatinine levels (8%), and hypokalemia (8%), without any treatment-related deaths. Conclusion: EGFR-TKI readministration with afatinib for sensitive EGFR-mutant NSCLC without T790M after resistance to a first- or second-generation EGFR-TKI yielded modest activity with tolerable toxicity. It might be one of the treatment options in patients who do not possess T790M tumors, although further studies in this patient setting are warranted.
AB - Purpose: The aim of this study was to evaluate the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) readministration using afatinib in patients with non-small-cell lung cancer (NSCLC) with a sensitive non-T790M EGFR mutation who had received cytotoxic chemotherapy after acquiring resistance to EGFR-TKIs. Methods: Eligible patients had EGFR-mutant tumors resistant to first- or second-generation EGFR-TKIs and an EGFR-TKI-free period with cytotoxic agents. Confirmation of absence of the T790M mutation was required before registration. Afatinib (40 mg/body) was administered daily. The primary endpoint was progression-free survival (PFS). We assumed estimated and threshold PFS times of 3.3 and 1 months, with an α of 0.05 and β of 0.1, respectively. Results: Twelve patients were enrolled from December 2014 to May 2017. The objective response rate and disease control rate were 17% and 84%, respectively. The median PFS time was 4.2 months (95% confidence interval [CI] 2.0–5.8), which met the pre-defined primary endpoint. The median overall survival was 11.6 months (95% CI 9.2-not reached). Grade 3 or worse adverse events included diarrhea (25%), elevated creatinine levels (8%), and hypokalemia (8%), without any treatment-related deaths. Conclusion: EGFR-TKI readministration with afatinib for sensitive EGFR-mutant NSCLC without T790M after resistance to a first- or second-generation EGFR-TKI yielded modest activity with tolerable toxicity. It might be one of the treatment options in patients who do not possess T790M tumors, although further studies in this patient setting are warranted.
KW - Afatinib
KW - EGFR mutation
KW - EGFR-TKI
KW - Non-small-cell lung cancer
KW - Readministration
KW - T790M
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U2 - 10.1007/s00280-018-3694-5
DO - 10.1007/s00280-018-3694-5
M3 - Article
C2 - 30276451
AN - SCOPUS:85054329444
SN - 0344-5704
VL - 82
SP - 1031
EP - 1038
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 6
ER -