Clinical Trial

. 2022 Dec 15;60(6):2200380.

doi: 10.1183/13993003.00380-2022. Print 2022 Dec.

Nintedanib plus chemotherapy for nonsmall cell lung cancer with idiopathic pulmonary fibrosis: a randomised phase 3 trial

Kohei Otsubo^{1

2}, Junji Kishimoto³, Masahiko Ando⁴, Hirotsugu Kenmotsu⁵, Yuji Minegishi^{6

7}, Hidehito Horinouchi⁸, Terufumi Kato⁹, Eiki Ichihara¹⁰, Masashi Kondo¹¹, Shinji Atagi¹², Motohiro Tamiya¹³, Satoshi Ikeda¹⁴, Toshiyuki Harada¹⁵, Shinnosuke Takemoto¹⁶, Hidetoshi Hayashi¹⁷, Keita Nakatomi¹⁸, Yuichiro Kimura¹⁹, Yasuhiro Kondoh²⁰, Masahiko Kusumoto²¹, Kazuya Ichikado²², Nobuyuki Yamamoto²³, Kazuhiko Nakagawa¹⁷, Yoichi Nakanishi^{1

24}, Isamu Okamoto²⁵

Affiliations

¹ Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
² Dept of Respiratory Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
³ Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan.
⁴ Dept of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan.
⁵ Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Japan.
⁶ Dept of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
⁷ Dept of Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan.
⁸ Dept of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁹ Dept of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan.
¹⁰ Dept of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
¹¹ Dept of Respiratory Medicine, Fujita Health University School of Medicine, Toyoake, Japan.
¹² Dept of Thoracic Oncology, National Hospital Organization Kinki-chuo Chest Medical Center, Sakai, Japan.
¹³ Dept of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
¹⁴ Dept of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.
¹⁵ Dept of Respiratory Medicine, JCHO Hokkaido Hospital, Sapporo, Japan.
¹⁶ Dept of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
¹⁷ Dept of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
¹⁸ Division of Respiratory Medicine, Kyushu Central Hospital, Fukuoka, Japan.
¹⁹ Dept of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan.
²⁰ Dept of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan.
²¹ Dept of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan.
²² Division of Respiratory Medicine, Saiseikai Kumamoto Hospital, Kumamoto, Japan.
²³ Internal Medicine III, Wakayama Medical University, Wakayama, Japan.
²⁴ Kitakyushu City Hospital Organization, Kitakyushu, Japan.
²⁵ Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan okamoto.isamu.290@m.kyushu-u.ac.jp.

PMID: 35361630
DOI: 10.1183/13993003.00380-2022

Free article

Clinical Trial

Nintedanib plus chemotherapy for nonsmall cell lung cancer with idiopathic pulmonary fibrosis: a randomised phase 3 trial

Kohei Otsubo et al. Eur Respir J. 2022.

Free article

. 2022 Dec 15;60(6):2200380.

doi: 10.1183/13993003.00380-2022. Print 2022 Dec.

Authors

Affiliations

¹ Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
² Dept of Respiratory Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
³ Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan.
⁴ Dept of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan.
⁵ Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Japan.
⁶ Dept of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
⁷ Dept of Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan.
⁸ Dept of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁹ Dept of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan.
¹⁰ Dept of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
¹¹ Dept of Respiratory Medicine, Fujita Health University School of Medicine, Toyoake, Japan.
¹² Dept of Thoracic Oncology, National Hospital Organization Kinki-chuo Chest Medical Center, Sakai, Japan.
¹³ Dept of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
¹⁴ Dept of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.
¹⁵ Dept of Respiratory Medicine, JCHO Hokkaido Hospital, Sapporo, Japan.
¹⁶ Dept of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
¹⁷ Dept of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
¹⁸ Division of Respiratory Medicine, Kyushu Central Hospital, Fukuoka, Japan.
¹⁹ Dept of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan.
²⁰ Dept of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan.
²¹ Dept of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan.
²² Division of Respiratory Medicine, Saiseikai Kumamoto Hospital, Kumamoto, Japan.
²³ Internal Medicine III, Wakayama Medical University, Wakayama, Japan.
²⁴ Kitakyushu City Hospital Organization, Kitakyushu, Japan.
²⁵ Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan okamoto.isamu.290@m.kyushu-u.ac.jp.

PMID: 35361630
DOI: 10.1183/13993003.00380-2022

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease implicated as an independent risk factor for lung cancer. However, optimal treatment for advanced lung cancer with IPF remains to be established. We performed a randomised phase 3 trial (J-SONIC) to assess the efficacy and safety of nintedanib plus chemotherapy (experimental arm) compared with chemotherapy alone (standard-of-care arm) for advanced nonsmall cell lung cancer (NSCLC) with IPF.

Methods: Chemotherapy-naïve advanced NSCLC patients with IPF were allocated to receive carboplatin (area under the curve of 6 on day 1) plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) (100 mg·m^-2 on days 1, 8 and 15) every 3 weeks with or without nintedanib (150 mg twice daily, daily). The primary end-point was exacerbation-free survival (EFS).

Results: Between May 2017 and February 2020, 243 patients were enrolled. Median EFS was 14.6 months in the nintedanib plus chemotherapy group and 11.8 months in the chemotherapy group (hazard ratio (HR) 0.89, 90% CI 0.67-1.17; p=0.24), whereas median progression-free survival was 6.2 and 5.5 months, respectively (HR 0.68, 95% CI 0.50-0.92). Overall survival was improved by nintedanib in patients with nonsquamous histology (HR 0.61, 95% CI 0.40-0.93) and in those at GAP (gender-age-physiology) stage I (HR 0.61, 95% CI 0.38-0.98). Seven (2.9%) out of 240 patients experienced acute exacerbation during study treatment.

Conclusions: The primary end-point of the study was not met. However, carboplatin plus nab-paclitaxel was found to be effective and tolerable in advanced NSCLC patients with IPF. Moreover, nintedanib in combination with such chemotherapy improved overall survival in patients with nonsquamous histology.

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Conflict of interest statement

Conflict of interest: K. Otsubo has received honoraria from Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly, Boehringer Ingelheim, ONO Pharmaceutical, AstraZeneca, Novartis, Merck and Thermo Fisher Scientific. H. Kenmotsu has received grants from Chugai Pharmaceutical, Novartis, Daiichi Sankyo, AstraZeneca and Loxo Oncology; and honoraria from Chugai Pharmaceutical, ONO Pharmaceutical, Boehringer Ingelheim, Eli Lilly, Kyowa Kirin, Bristol-Myers Squibb, MSD, Novartis, Daiichi Sankyo, AstraZeneca, Pfizer and Taiho Pharmaceutical. Y. Minegishi has received honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, ONO Pharmaceutical, Taiho Pharmaceutical and Chugai Pharmaceutical. H. Horinouchi has received grants from MSD, AbbVie, AstraZeneca, Bristol-Myers Squibb, ONO Pharmaceutical, Merck, Daiichi Sankyo, Janssen, Genomic Health, Chugai Pharmaceutical, Roche and Novartis; honoraria from AstraZeneca, MSD, Eli Lilly, ONO Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, Roche, Kyowa Kirin and Novartis; and fees for membership of an advisory board from Roche, AstraZeneca, Eli Lilly, Chugai Pharmaceutical, Roche, ONO Pharmaceutical, Bristol-Myers Squibb and MSD. T. Kato received grants from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Merck, MSD, Novartis, ONO Pharmaceutical, Pfizer and Regeneron; honoraria from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Merck, MSD, Novartis, Pfizer and Boehringer Ingelheim; fees for membership of an advisory board from AbbVie, AstraZeneca, Daiichi Sankyo, MSD, Merck, Amgen, Chugai Pharmaceutical, Eli Lilly, Novartis and Nippon Kayaku; and fees for membership of an independent data monitoring committee from Chugai Pharmaceutical, Taiho Pharmaceutical, Takeda and ONO Pharmaceutical. E. Ichihara has received grants from Eli Lilly and MSD; and honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Bristol-Myers Squibb, Novartis, ONO Pharmaceutical, Taiho Pharmaceutical, Takeda and Chugai Pharmaceutical. M. Kondo has received consulting fees from Takeda; and honoraria from Chugai Pharmaceutical, Eli Lilly, Pfizer, AstraZeneca, ONO Pharmaceutical, Bristol-Myers Squibb and MSD. S. Atagi has received grants from AstraZeneca, Eli Lilly, ONO Pharmaceutical, Taiho Pharmaceutical, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, MSD, Chugai Pharmaceutical, Merck and Roche; and honoraria from AstraZeneca, Eli Lilly, ONO Pharmaceutical, Taiho Pharmaceutical, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, Hisamitsu Pharmaceutical, MSD, Chugai Pharmaceutical, Kyowa Kirin, Merck, Novartis and Thermo Fisher Scientific. M. Tamiya has received grants and honoraria from Boehringer Ingelheim. S. Ikeda has received grants from AstraZeneca and Chugai Pharmaceutical; and honoraria from Chugai Pharmaceutical, ONO Pharmaceutical, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, AstraZeneca, Pfizer and Taiho Pharmaceutical. H. Hayashi has received reports grants from AstraZeneca, Astellas, MSD, ONO Pharmaceutical, Boehringer Ingelheim, Novartis, Pfizer, Bristol-Myers Squibb, Eli Lilly, Chugai Pharmaceutical, Daiichi Sankyo, Merck, Takeda, Taiho Pharmaceutical, SymBio Pharmaceuticals, AbbVie, inVentiv Health Japan, ICON Japan, Gritsone Oncology, Parexel, Kissei Pharmaceutical, EPS Corporation, Syneos Health, Pfizer R&D Japan, A2 Healthcare, IQVIA, EP-CRSU, Eisai, CMIC Shift Zero, Kyowa Kirin, Bayer Yakuhin, EPS and Otsuka Pharmaceutical; consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Pfizer, Shanghai Haihe Biopharm, Takeda and Merck; and honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Kyorin, Merck, Ltd, MSD, Novartis, ONO Pharmaceutical, Taiho Pharmaceutical and Takeda. Y. Kimura has received honoraria from AstraZeneca, Boehringer Ingelheim and Taiho Pharmaceutical. Y. Kondoh has received honoraria from Asahi Kasei Pharma, Shionogi, Boehringer Ingelheim, AstraZeneca, Eisai, Kyorin, Mitsubishi Tanabe Pharma and Novartis; and fees for membership of a data safety monitoring board or an advisory board from Asahi Kasei Pharma, Shionogi, Boehringer Ingelheim, Janssen, Healios, Chugai Pharmaceutical and Taiho Pharmaceutical. M. Kusumoto has received grants from Canon medical systems; and honoraria from AstraZeneca and Daiichi Sankyo. N. Yamamoto has received honoraria from MSD, AstraZeneca, ONO Pharmaceutical, Thermo Fisher Scientific, Daiichi Sankyo, Taiho Pharmaceutical, Takeda, Chugai Pharmaceutical, Eli Lilly, Boehringer Ingelheim, Novartis, Pfizer, Bristol-Myers Squibb, Nippon Kayaku, GlaxoSmithKline, Sanofi, Hisamitsu Pharmaceutical and Merck; and fees for membership of a data safety monitoring board or an advisory board from MSD, AstraZeneca, ONO Pharmaceutical, Taiho Pharmaceutical, Takeda, Chugai Pharmaceutical, Eli Lilly, Boehringer Ingelheim, Novartis, Pfizer, Bristol-Myers Squibb, Life Technologies Japan, Nippon Kayaku, Amgen, Guardant Health and Janssen. K. Nakagawa has received grants from Takeda, Taiho Pharmaceutical, SymBio Pharmaceuticals, AbbVie, ICON, Parexel, Kissei Pharmaceutical, EPS, Syneos Health, Pfizer R&D Japan, A2 Healthcare, IQVIA, Eisai, CMIC Shift Zero, Kyowa Kirin, Bayer Yakuhin, Otsuka Pharmaceutical, PRA Health Sciences, Covance, Medical Research Support, Sanofi, PPD-SNBL, Japan Clinical Research Operations, Sysmex, Mochida Pharmaceutical and GlaxoSmithKline; honoraria from AstraZeneca, Chugai Pharmaceutical, Takeda, Roche, MSD, Eli Lilly, Nippon Kayaku, ONO Pharmaceutical, Astellas, Bayer Yakuhin, Merck, Nanzando, Daiichi Sankyo, Novartis, Kyowa Kirin, Medical Mobile Communications, Yomiuri Telecasting Corporation, Nikkei Business Publications, Boehringer Ingelheim, Medicus Shuppan, Taiho Pharmaceutical, Pfizer, AbbVie, Bristol-Myers Squibb, CareNet, Amgen, Medical Review, Yodosha, 3H Clinical Trial, Thermo Fisher Scientific, Hisamitsu Pharmaceutical, Nichi-Iko Pharmaceutical and Kyorin; and payment for expert testimony from Astellas, Takeda, Eli Lilly, Pfizer, Kyorin and ONO Pharmaceutical. Y. Nakanishi has received grants from ONO Pharmaceutical; and honoraria from MSD, ONO Pharmaceutical, AstraZeneca, Pfizer and Boehringer Ingelheim. I. Okamoto has received grants from AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, ONO Pharmaceutical, MSD, Eli Lilly, Astellas, Bristol-Myers Squibb, Novartis, Chugai Pharmaceutical, Pfizer and AbbVie; consulting fees from AstraZeneca, Bristol-Myers Squibb and AbbVie; and honoraria from AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, ONO Pharmaceutical, MSD, Eli Lilly, Bristol-Myers Squibb, Novartis, Chugai Pharmaceutical and Pfizer. All other authors declare no competing interests.

Comment in

Lung cancer in pulmonary fibrosis: no room for nihilism!
Crestani B, Kolb M. Crestani B, et al. Eur Respir J. 2022 Dec 15;60(6):2201946. doi: 10.1183/13993003.01946-2022. Print 2022 Dec. Eur Respir J. 2022. PMID: 36522141 No abstract available.

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Nintedanib plus chemotherapy for nonsmall cell lung cancer with idiopathic pulmonary fibrosis: a randomised phase 3 trial

Affiliations

Nintedanib plus chemotherapy for nonsmall cell lung cancer with idiopathic pulmonary fibrosis: a randomised phase 3 trial

Authors

Affiliations

Abstract

Conflict of interest statement

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