Skin disorder within 30 days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study

Fumihiko Kinoshita¹, Shigeru Tanzawa², Toshihiro Misumi³, Hiroshige Yoshioka⁴, Eisaku Miyauchi⁵, Kiichiro Ninomiya⁶, Yasunori Murata⁷, Masafumi Takeshita⁷, Masafumi Yamaguchi¹, Shunichi Sugawara⁸, Yosuke Kawashima⁸, Kazuki Hashimoto⁹, Masahide Mori⁹, Akihiko Miyanaga¹⁰, Anna Hayashi¹⁰, Hisashi Tanaka¹¹, Ryoichi Honda¹², Masafumi Nojiri¹³, Yuki Sato¹⁴, Ken Yamamoto¹⁵, Ken Masuda¹⁶, Toshiyuki Kozuki¹⁷, Takahisa Kawamura¹⁸, Takuji Suzuki¹⁹, Teppei Yamaguchi²⁰, Kazuhiro Asada²¹, Satoshi Tetsumoto²², Hiroshi Tanaka²³, Satoshi Watanabe²⁴, Yukihiro Umeda²⁵, Kakuhiro Yamaguchi²⁶, Shoichi Kuyama²⁷, Kosuke Tsuruno²⁸, Yuki Misumi²⁹, Hiroshi Kuraishi³⁰, Ken Yoshihara³¹, Akira Nakao³², Akihito Kubo³³, Toshihiko Yokoyama³⁴, Kana Watanabe³⁵, Nobuhiko Seki²

Affiliations

¹ Department of Thoracic Oncology, NHO Kyushu Cancer Center, Fukuoka, Japan.
² Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
³ Department of Data Science, National Cancer Center Hospital East, Chiba, Japan.
⁴ Department of Thoracic Oncology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata 573-1010, Japan.
⁵ Department of Respiratory Medicine, Tohoku University Hospital, Miyagi, Japan.
⁶ Center for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan.
⁷ Department of Respiratory Medicine, Ichinomiya Nishi Hospital, Aichi, Japan.
⁸ Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan.
⁹ Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center, Osaka, Japan.
¹⁰ Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
¹¹ Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Aomori, Japan.
¹² Department of Respiratory Medicine, Asahi General Hospital, Chiba, Japan.
¹³ Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa, Japan.
¹⁴ Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Hyogo, Japan.
¹⁵ Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center, Hyogo, Japan.
¹⁶ Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan.
¹⁷ Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center, Ehime, Japan.
¹⁸ Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
¹⁹ Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
²⁰ Department of Thoracic Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
²¹ Department of Respiratory Medicine, Shizuoka General Hospital, Shizuoka, Japan.
²² Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital, Osaka, Japan.
²³ Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.
²⁴ Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
²⁵ Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
²⁶ Department of Respiratory Medicine, Hiroshima University Hospital, Hiroshima, Japan.
²⁷ Department of Respiratory medicine, NHO Iwakuni Clinical Center, Yamaguchi, Japan.
²⁸ Department of Respiratory Medicine, Iizuka Hospital, Fukuoka, Japan.
²⁹ Department of Respiratory Medicine, Yokohama Municipal Citizen's Hospital, Kanagawa, Japan.
³⁰ Department of Respiratory Medicine, Nagano Red Cross Hospital, Nagano, Japan.
³¹ Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, Shimane, Japan.
³² Department of Respiratory Medicine, Fukuoka University Hospital, Fukuoka, Japan.
³³ Department of Respiratory Medicine and Allergology, Aichi Medical University School of Medicine, Aichi, Japan.
³⁴ Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Aichi, Japan.
³⁵ Department of Respiratory Medicine, Miyagi Cancer Center, Miyagi, Japan.

PMID: 40093977
PMCID: PMC11909677
DOI: 10.1177/17588359241312503

Skin disorder within 30 days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study

Fumihiko Kinoshita et al. Ther Adv Med Oncol. 2025.

. 2025 Mar 15:17:17588359241312503.

doi: 10.1177/17588359241312503. eCollection 2025.

Authors

Affiliations

¹ Department of Thoracic Oncology, NHO Kyushu Cancer Center, Fukuoka, Japan.
² Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
³ Department of Data Science, National Cancer Center Hospital East, Chiba, Japan.
⁴ Department of Thoracic Oncology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata 573-1010, Japan.
⁵ Department of Respiratory Medicine, Tohoku University Hospital, Miyagi, Japan.
⁶ Center for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan.
⁷ Department of Respiratory Medicine, Ichinomiya Nishi Hospital, Aichi, Japan.
⁸ Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan.
⁹ Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center, Osaka, Japan.
¹⁰ Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
¹¹ Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Aomori, Japan.
¹² Department of Respiratory Medicine, Asahi General Hospital, Chiba, Japan.
¹³ Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa, Japan.
¹⁴ Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Hyogo, Japan.
¹⁵ Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center, Hyogo, Japan.
¹⁶ Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan.
¹⁷ Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center, Ehime, Japan.
¹⁸ Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
¹⁹ Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
²⁰ Department of Thoracic Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
²¹ Department of Respiratory Medicine, Shizuoka General Hospital, Shizuoka, Japan.
²² Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital, Osaka, Japan.
²³ Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.
²⁴ Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
²⁵ Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
²⁶ Department of Respiratory Medicine, Hiroshima University Hospital, Hiroshima, Japan.
²⁷ Department of Respiratory medicine, NHO Iwakuni Clinical Center, Yamaguchi, Japan.
²⁸ Department of Respiratory Medicine, Iizuka Hospital, Fukuoka, Japan.
²⁹ Department of Respiratory Medicine, Yokohama Municipal Citizen's Hospital, Kanagawa, Japan.
³⁰ Department of Respiratory Medicine, Nagano Red Cross Hospital, Nagano, Japan.
³¹ Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, Shimane, Japan.
³² Department of Respiratory Medicine, Fukuoka University Hospital, Fukuoka, Japan.
³³ Department of Respiratory Medicine and Allergology, Aichi Medical University School of Medicine, Aichi, Japan.
³⁴ Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Aichi, Japan.
³⁵ Department of Respiratory Medicine, Miyagi Cancer Center, Miyagi, Japan.

PMID: 40093977
PMCID: PMC11909677
DOI: 10.1177/17588359241312503

Abstract

Background: Skin disorders are major adverse events associated with necitumumab plus gemcitabine and cisplatin (Neci + GC) administration. However, the prognostic effect of skin disorders in patients with lung squamous cell carcinoma (LSCC) administered Neci + GC is unclear.

Objectives: We examined this prognostic effect in patients with LSCC, and the usefulness of minocycline administration.

Design: This was a sub-analysis of the retrospective multicenter NINJA study.

Methods: We performed a landmark survival analysis according to the presence of skin disorders at Day 30 of treatment and examined the usefulness of minocycline for treating skin disorders.

Results: Among the 93 patients, 62 (66.7%) had a skin disorder at Day 30. Nineteen, 30, and 13 patients experienced Grade 1, 2, and 3 skin disorders, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with skin disorders at Day 30 were longer than those of patients without skin disorders (median OS: 434 vs 278 days, p = 0.0201; median PFS: 148 vs 82 days, p = 0.0835). Multivariable analysis showed that a skin disorder at Day 30 was an independent prognostic factor for both OS (p = 0.0044) and PFS (p = 0.0514). Of the 62 patients with skin disorders at Day 30, 38 (61.3%) were taking minocycline, and their time to treatment failure (TTF) was better than that in patients not taking minocycline (median TTF: 148 vs 101 days, p = 0.0495).

Conclusion: A skin disorder within 30 days was a favorable prognostic factor for patients with LSCC administered Neci + GC. Additionally, minocycline administration may be beneficial in patients who develop skin disorders within 30 days.

Keywords: adverse event; lung cancer; necitumumab; skin disorder; squamous cell carcinoma.

PubMed Disclaimer

Conflict of interest statement

F.K.: Nippon Kayaku, Eisai, Taiho Pharmaceutical, Eli Lilly Japan, Ono Pharmaceutical, Takeda Pharmaceutical. Shigeru Tanzawa: Nippon Kayaku, AstraZeneca, Chugai Pharmaceutical, MSD. T.M.: Nippon Kayaku, Chugai Pharmaceutical, AstraZeneca. H.Y.: Delta Fly Pharma, Nippon Kayaku, Boehringer Ingelheim, Chugai pharmaceutical, Taiho Pharmaceutical, Novartis Pharma, Ono Pharmaceutical, AstraZeneca, MSD, Bristol-Myers Squibb, Pfizer, Eli Lilly, Otsuka Pharmaceutical, Daiichi Sankyo, Amgen, Pfizer, Merck, and Kyowa Kirin. E.M.: Nippon Kayaku, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, Daiichi Sankyo, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, MSD, Kyowa Kirin, Merck Biopharma, Pfizer, Ono Pharmaceutical, Eisai, Otsuka pharmaceutical, Amgen, Thermo Fisher Scientific, Takeda Pharmaceutical, Sysmex. K.N.: Nippon Kayaku, AstraZeneca, Boehringer-Ingelheim, Kyowa Kirin, Lilly Japan, Chugai Pharmaceutical Nippon Kayaku, Taiho Pharmaceutical, MSD, Ono Pharmaceutical, Novartis Pharma, Takeda Pharmaceutical, Pfizer, Bristol Myers Squibb, Elekta K.K. Yasunori Murata: Nippon Kayaku, AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim. M.T.: Nippon Kayaku, Taiho Pharmaceutical Co. Ltd, AstraZeneca, Boehringer Ingelheim Japan Inc., Bristol Myers Squibb Co. Ltd, Novartis Pharma KK, MSD KK, Kyowa Kirin Co. Ltd, Ono Pharmaceutical Co. Ltd, Chugai Pharmaceutical Co. Ltd, Takeda Pharmaceutical Co. Ltd, Eli Lilly Japan KK. M.Y.: Nippon Kayaku, AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, MSD, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical. S.S.: Nippon Kayaku, AstraZeneca, Chugai Pharma, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Nippon Boehringer Ingelheim, Pfizer, Taiho Pharmaceutical, Eli Lilly and Company, Novartis, Kyowa Kirin, Takeda, Merck, Amgen, AbbVie, Otsuka, Thermo Fisher Scientific, Eisai, AnHeart, Daiichi Sankyo, Accerise. Y.K.: Nippon Kayaku, Taiho Pharmaceutical, Eli Lilly, Life Technologies Japan Ltd, Chugai Pharma, AstraZeneca, Kyowa Kirin, Japan. K.H.: Nippon Kayaku. M.M.: Nippon Kayaku, Astrazeneca, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eli Lilly, Kyowa-kirin, MSD, Ono Pharmaceutical, Pfizer, Taiho, Takeda, AbbVie Inc. A.M.: AstraZeneca, Nippon Kayaku, Merck, Kyowa Kirin, Pfizer, Inc., Takeda Pharmaceutical. A.H.: Nippon Kayaku. Hisashi Tanaka: Nippon Kayaku, Ono Pharmaceutical Co. Ltd, Bristol Myers Squibb, AstraZeneca, Chugai Pharmaceutical Co., Boehringer-Ingelheim Japan Inc., Pfizer Japan Inc., Takeda. R.H.: Nippon Kayaku. M.N.: Nippon Kayaku. Y.S.: Nippon Kayaku, AstraZeneca, MSD, Novartis, Chugai Pharmaceutical, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Bristol Myers Squibb, Eli Lilly, Takeda, Kyowa Kirin, Daiichi Sankyo. Ken Yamamoto: Nippon Kayaku. Ken Masuda: Nippon Kayaku. Toshiyuki Kozuki: Nippon Kayaku, Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical Co., Bristol-Myers Squibb, Ono Pharmaceutical Co., MSD, Pfizer Japan, Kyowa Hakko Kirin, Nippon Boehringer Ingelheim, Merck Biopharma, Novartis, Daiichi-Sankyo, Takeda Pharmaceutical Co., Bayer, Sawai, AMGEN, Eisai, Abbvie, Sanofi, Labcorp Development Japan, IQVIA Services Japan, Gilead Sciences. Takahisa Kawamura: Nippon Kayaku. Takuji Suzuki: Nippon Kayaku, AstraZeneca, Nippon Boehringer Ingelheim Co., Ltd. Teppei Yamaguchi: Nippon Kayaku, Ono Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, MSD, Bristol-Meyers Squibb. K.A.: Nippon Kayaku, AstraZeneca, Chugai Pharmaceutical. Satoshi Tetsumoto: Nippon Kayaku. Hiroshi Tanaka: Nippon Kayaku, Astra Zeneca, Chugai Pharmaceutical, MSD, Ono Pharmaceutical, Bristol Myers Squibb, Daiichi-Sankyo pharmaceutical, Eli Lilly, Takeda Pharmaceutical, Taiho Pharmaceutical, Merck, Boehringer Ingelheim, Amgen, Abbvie, Sun Pharmaceutical, Eisai, Novartis, Pfizer, Celltrion. S.W.: Nippon Kayaku, Lilly, Chugai Pharma, Ono Pharmaceutical, Taiho Pharmaceutical, Kyowa Kirin, Takeda Pharmaceutical, AstraZeneca, Novartis Pharma, Bristol-Myers, Daiichi Sankyo, Merck, Celltrion. Y.U.: Nippon Kayaku. Kakuhiro Yamaguchi: Nippon Kayaku. S.K.: Nippon Kayaku, Chugai Pharmaceutical Co., Ltd, Boehringer Ingelheim, Pfizer, MSD, Kyowa Kirin Co., Ltd, DAIICHI SANKYO COMPANY, LIMITED, Novartis, Bristol-Myers Squibb Company, AstraZenca, Eli Lilly, TAIHO PHARMACEUTICAL CO., LTD, Hisamitsu Pharmaceutical Co., Inc. KT: Nippon Kayaku. Yuki Misumi: Nippon Kayaku, BeiGene, Eli Lilly, AstraZeneca, AbbVie, Ono Pharmaceutical, Taiho Pharmaceutical, Novartis, Boehringer Ingelheim, Nobel pharma, Bristol Myers Squibb. H.K.: Nippon Kayaku. Ken Yoshihara: Nippon Kayaku. A.N.: Nippon Kayaku. A.K.: Nippon Kayaku, Chugai, Astra Zeneca, Lilly, Ono Pharmaceuticals, Takeda, MSD. Toshihiko Yokoyama: Nippon Kayaku. K.W.: Nippon Kayaku. N.S.: Nippon Kayaku, Eli Lilly, AstraZeneca, MSD, Chugai Pharmaceutical, Taiho Pharmaceutical, Pfizer, Ono Pharmaceutical, Takeda Pharmaceutical, Daiichi Sankyo, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Merck.

Figures

**Figure 1.**
A flow diagram of the patients’ characteristics and landmark survival analyses.

**Figure 2.**
Survival curves of OS (a) and PFS (b) according to the presence of skin disorders at Day 30. Survival curves of OS (c) and PFS (d) according to the grade of skin disorders at Day 30. OS, overall survival; PFS, progression-free survival.

**Figure 3.**
Survival curves of overall survival (a), progression-free survival (b), and time to treatment failure (c) according to the administration of minocycline in patients with skin disorders at Day 30.

See this image and copyright information in PMC

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Skin disorder within 30 days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study

Affiliations

Skin disorder within 30 days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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Full Text Sources

Miscellaneous