Development of a novel therapeutic strategy for lung cancer with interstitial pneumonia - from the viewpoint of chemoprevention -

• Project/Area Number: 18K15925
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Okayama University
• Principal Investigator: Kubo Toshio 岡山大学, 大学病院, 助教 (90726928)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 間質性肺炎 / 肺癌 / 化学予防

Outline of Final Research Achievements

The treatment for lung cancer patients with interstitial pneumonia is difficult because of the risk of acute exacerbation and low lung function. This time, we examined the chemo-preventive effect of nintedanib, which is a drug for interstitial pneumonia. From the results of the gene profile, it was considered difficult to prevent the development of lung cancer with nintedanib. A multicenter, retrospective analysis revealed that the lung cancer incidence of nintedanib and pirfenidone, an anti-fibrotic drug used for interstitial pneumonia, were 1.2 vs 2.6 per 100 person-years (P = 0.33, Gray test), and no statistically significant difference was observed.
From this study, we could not obtain the expected results regarding the chemo-preventive effect of nintedanib on lung cancer development.

Academic Significance and Societal Importance of the Research Achievements

間質性肺炎に肺癌を合併する頻度は高いが、急性増悪のリスクや低肺機能のため、治療介入が難しいことが多い。今回は治療介入が難しい間質性肺炎合併肺癌に対し、いかに発癌を予防するかという観点から新規治療戦略の開発を目指した。今回の検討では、発癌予防の候補薬剤と考えていたニンテダニブについて期待できる結果は得られなかったが、間質性肺炎合併肺癌の予後は不良であり、発癌予防に観点をおいた治療戦略の開発は今後も重要と考えられる。

Research Products

• [Journal Article] Rapid and Long-term Response of Pulmonary Pleomorphic Carcinoma to Nivolumab (2019)
  • Author(s): Senoo Satoru、Ninomiya Takashi、Makimoto Go、Nishii Kazuya、Kano Hirohisa、Watanabe Hiromi、Hata Yusuke、Kubo Toshio、Tanaka Takehiro、Hotta Katsuyuki、Maeda Yoshinobu、Kiura Katsuyuki
  • Journal Title: Internal Medicine Volume: 58 Issue: 7 Pages: 985-989
  • DOI: 10.2169/internalmedicine.0890-18
  • NAID: 130007622179
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2019-04-01
  • Peer Reviewed
• [Journal Article] Influence of age on the efficacy of immune checkpoint inhibitors in advanced cancers: a systematic review and meta-analysis (2019)
  • Author(s): Ninomiya Kiichiro、Oze Isao、Kato Yuka、Kubo Toshio、Ichihara Eiki、Rai Kammei、Ohashi Kadoaki、Kozuki Toshiyuki、Tabata Masahiro、Maeda Yoshinobu、Kiura Katsuyuki、Hotta Katsuyuki
  • Journal Title: Acta Oncologica Volume: 59 Issue: 3 Pages: 249-256
  • DOI: 10.1080/0284186x.2019.1695062
  • Peer Reviewed
• [Journal Article] Patients’ preferences and perceptions of lung cancer treatment decision making: results from Okayama lung cancer study group trial 1406 (2019)
  • Author(s): Makimoto Go、Hotta Katsuyuki、Oze Isao、Ninomiya Kiichiro、Nakanishi Masamoto、Hara Naofumi、Kano Hirohisa、Watanabe Hiromi、Hata Yusuke、Nishii Kazuya、Nakasuka Takamasa、Itano Junko、Ninomiya Takashi、Kubo Toshio、Ohashi Kadoaki、Ichihara Eiki、Tabata Masahiro、Maeda Yoshinobu、Kiura Katsuyuki
  • Journal Title: Acta Oncologica Volume: 59 Issue: 3 Pages: 324-328
  • DOI: 10.1080/0284186x.2019.1679880
  • Peer Reviewed
• [Journal Article] Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden. (2019)
  • Author(s): Makimoto G, Ohashi K, Tomida S, Nishii K, Matsubara T, Kayatani H, Higo H, Ninomiya K, Sato A, Watanabe H, Kano H, Ninomiya T, Kubo T, Rai K, Ichihara E, Hotta K, Tabata M, Toyooka S, Takata M, Maeda Y, Kiura K.
  • Journal Title: J Thorac Oncol. Volume: 11 Issue: 11 Pages: 2009-2018
  • DOI: 10.1016/j.jtho.2019.07.017
  • NAID: 120006871852
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Programmed cell death-ligand 1 expression and efficacy of cisplatin-based chemotherapy in lung cancer: A sub-analysis of data from the two Okayama Lung Cancer Study Group prospective feasibility studies (2019)
  • Author(s): Nishii Kazuya、Hotta Katsuyuki、Ninomiya Kiichiro、Kato Yuka、Ichihara Eiki、Ohashi Kadoaki、Ninomiya Takashi、Kubo Toshio、Rai Kammei、Tabata Masahiro、Maeda Yoshinobu、Kiura Katsuyuki
  • Journal Title: Respiratory Investigation Volume: 57 Issue: 5 Pages: 460-465
  • DOI: 10.1016/j.resinv.2019.04.004
  • Peer Reviewed
• [Journal Article] Re-administration of osimertinib in osimertinib-acquired resistant non-small-cell lung cancer (2019)
  • Author(s): Ichihara Eiki、Hotta Katsuyuki、Ninomiya Kiichiro、Kubo Toshio、Ohashi Kadoaki、Rai Kammei、Tanaka Hisaaki、Tabata Masahiro、Maeda Yoshinobu、Kiura Katsuyuki
  • Journal Title: Lung Cancer Volume: 132 Pages: 54-58
  • DOI: 10.1016/j.lungcan.2019.02.021
  • Peer Reviewed
• [Journal Article] The effect and safety of immune checkpoint inhibitor rechallenge in non-small cell lung cancer (2019)
  • Author(s): Watanabe Hiromi、Kubo Toshio、Ninomiya Kiichiro、Kudo Kenichiro、Minami Daisuke、Murakami Etsuko、Ochi Nobuaki、Ninomiya Takashi、Harada Daijiro、Yasugi Masayuki、Ichihara Eiki、Ohashi Kadoaki、Fujiwara Keiichi、Hotta Katsuyuki、Tabata Masahiro、Maeda Yoshinobu、Kiura Katsuyuki
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 49 Issue: 8 Pages: 762-765
  • DOI: 10.1093/jjco/hyz066
  • Peer Reviewed
• [Journal Article] A phase I/II trial of weekly nab‐paclitaxel for pretreated non‐small‐cell lung cancer patients without epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement (2019)
  • Author(s): Harada Daijiro、Kozuki Toshiyuki、Nogami Naoyuki、Bessho Akihiro、Hosokawa Shinobu、Fukamatsu Nobuaki、Hotta Katsuyuki、Ohashi Kadoaki、Kubo Toshio、Yoshioka Hiroshige、Yokoyama Toshihide、Sone Naoyuki、Kuyama Shoichi、Kudo Kenichiro、Yasugi Masayuki、Takigawa Nagio、Oze Isao、Kiura Katsuyuki
  • Journal Title: Asia-Pacific Journal of Clinical Oncology Volume: 15 Issue: 4 Pages: 250-256
  • DOI: 10.1111/ajco.13147
  • Peer Reviewed
• [Journal Article] Chemoradiotherapy for locally advanced lung cancer patients with interstitial lung abnormalities (2019)
  • Author(s): Higo Hisao、Kubo Toshio、Makimoto Satoko、Makimoto Go、Ihara Hiroki、Masaoka Yoshihisa、Ninomiya Takashi、Ichihara Eiki、Ohashi Kadoaki、Sato Akiko、Hotta Katsuyuki、Tabata Masahiro、Takigawa Nagio、Maeda Yoshinobu、Kiura Katsuyuki
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 49 Issue: 5 Pages: 458-464
  • DOI: 10.1093/jjco/hyz016
  • Peer Reviewed
• [Journal Article] Atezolizumab Treatment Beyond Progression in Advanced NSCLC: Results From the Randomized, Phase III OAK Study (2018)
  • Author(s): Gandara David R.、von Pawel Joachim、Mazieres Julien、Sullivan Richard、Helland ?slaug、Han Ji-Youn、Ponce Aix Santiago、Rittmeyer Achim、Barlesi Fabrice、Kubo Toshio、Park Keunchil、Goldschmidt Jerome、Gandhi Mayank、Yun Cindy、Yu Wei、Matheny Christina、He Pei、Sandler Alan、Ballinger Marcus、Fehrenbacher Louis
  • Journal Title: Journal of Thoracic Oncology Volume: 13 Issue: 12 Pages: 1906-1918
  • DOI: 10.1016/j.jtho.2018.08.2027
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Combined effect of cabozantinib and gefitinib in crizotinib-resistant lung tumors harboring ROS1 fusions (2018)
  • Author(s): Kato Yuka、Ninomiya Kiichiro、Ohashi Kadoaki、Tomida Shuta、Makimoto Go、Watanabe Hiromi、Kudo Kenichiro、Matsumoto Shingo、Umemura Shigeki、Goto Koichi、Ichihara Eiki、Ninomiya Takashi、Kubo Toshio、Sato Akiko、Hotta Katsuyuki、Tabata Masahiro、Toyooka Shinichi、Maeda Yoshinobu、Kiura Katsuyuki
  • Journal Title: Cancer Science Volume: 109 Issue: 10 Pages: 3149-3158
  • DOI: 10.1111/cas.13752
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of repeat rebiopsy in detecting the EGFR T790M secondary mutation in patients with non-small cell lung cancer (2018)
  • Author(s): Ichihara Eiki、Hotta Katsuyuki、Kubo Toshio、Higashionna Tsukasa、Ninomiya Kiichiro、Ohashi Kadoaki、Tabata Masahiro、Maeda Yoshinobu、Kiura Katsuyuki
  • Journal Title: Oncotarget Volume: 9 Issue: 50 Pages: 29525-29531
  • DOI: 10.18632/oncotarget.25705
  • Peer Reviewed / Open Access
• [Journal Article] Atezolizumab in Japanese Patients With Previously Treated Advanced Non?Small-Cell Lung Cancer: A Subgroup Analysis of the Phase 3 OAK Study (2018)
  • Author(s): Hida Toyoaki、Kaji Reiko、Satouchi Miyako、Ikeda Norihiko、Horiike Atsushi、Nokihara Hiroshi、Seto Takashi、Kawakami Tomohisa、Nakagawa Shintaro、Kubo Toshio
  • Journal Title: Clinical Lung Cancer Volume: 19 Issue: 4 Pages: e405-e415
  • DOI: 10.1016/j.cllc.2018.01.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Second primary cancer in survivors of locally advanced non-small cell lung cancer treated with concurrent chemoradiation followed by surgery (2018)
  • Author(s): Makimoto Go、Kubo Toshio、Oze Isao、Ohashi Kadoaki、Hotta Katsuyuki、Tabata Masahiro、Soh Junichi、Toyooka Shinichi、Katsui Kuniaki、Takigawa Nagio、Tanimoto Mitsune、Kiura Katsuyuki
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 48 Issue: 3 Pages: 287-290
  • DOI: 10.1093/jjco/hyy003
  • Peer Reviewed
• [Journal Article] MET or NRAS amplification is an acquired resistance mechanism to the third-generation EGFR inhibitor naquotinib (2018)
  • Author(s): Ninomiya Kiichiro、Ohashi Kadoaki、Makimoto Go、Tomida Shuta、Higo Hisao、Kayatani Hiroe、Ninomiya Takashi、Kubo Toshio、Ichihara Eiki、Hotta Katsuyuki、Tabata Masahiro、Maeda Yoshinobu、Kiura Katsuyuki
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1955-1955
  • DOI: 10.1038/s41598-018-20326-z
  • Peer Reviewed / Open Access
• [Journal Article] A Phase II Study of Trastuzumab Emtansine in HER2-Positive Non-Small Cell Lung Cancer (2018)
  • Author(s): Hotta Katsuyuki、Aoe Keisuke、Kozuki Toshiyuki、Ohashi Kadoaki、Ninomiya Kiichiro、Ichihara Eiki、Kubo Toshio、Ninomiya Takashi、Chikamori Kenichi、Harada Daijiro、Nogami Naoyuki、Hirata Taizo、Hinotsu Shiro、Toyooka Shinichi、Kiura Katsuyuki
  • Journal Title: Journal of Thoracic Oncology Volume: 13 Issue: 2 Pages: 273-279
  • DOI: 10.1016/j.jtho.2017.10.032
  • Peer Reviewed
• [Journal Article] A phase I trial of afatinib and bevacizumab in chemo-naive patients with advanced non-small-cell lung cancer harboring EGFR mutations: Okayama Lung Cancer Study Group Trial 1404. (2018)
  • Author(s): Ninomiya T, Nogami N, Kozuki T, Harada D, Kubo T, Ohashi K, Kuyama S, Kudo K, Bessho A, Fukamatsu N, Fujimoto N, Aoe K, Shibayama T, Sugimoto K, Takigawa N, Hotta K, Kiura K.
  • Journal Title: Lung Cancer. Volume: 115 Pages: 103-108
  • DOI: 10.1016/j.lungcan.2017.11.025
  • Peer Reviewed
• [Presentation] Significant combination benefit of anti-VEGFR antibody and oncogene-targeted agents in EGFR or ALK mutant NSCLC cells. (2019)
  • Author(s): Watanabe H, Ichihara E, Kayatani H, Higo G, Makimoto G, Kano H, Nishii K, Hara N, Ninomiya K, Kubo T, Ohashi K, Rai K, Hotta K, Tabata M, Maeda Y, Kiura K.
  • Organizer: AACR Annual Meeting
  • Int'l Joint Research
• [Presentation] Updated analysis of a phase I trial of afatinib (Afa) and bevacizumab (Bev) in chemo-naive patients (pts) with advanced non-small-cell lung cancer (NSCLC) harboring EGFR-mutations: OLCSG1404. (2019)
  • Author(s): Ninomiya T, Nogami N, Kozuki T, Harada D, Kubo T, Ohashi K, Kuyama S, Kudo K, Bessho A, Fujimoto N, Aoe K, Shibayama T, Minami D, Sugimoto K, Ochi N, Takigawa N, Hotta K, Kiura K.
  • Organizer: ESMO Annual Meeting
  • Int'l Joint Research
• [Presentation] Phase II trial of carboplatin, nab-paclitaxel and bevacizumab for advanced non-squamous non-small cell lung cancer (CARNAVAL study; TORG1424/OLCSG1402). (2019)
  • Author(s): Kubo T, Nogami N, Bessho A, Morita A, Ikeo S, Yokoyama T, Ishihara M, Honda T, Fujimoto N, Murakami S, Kaira K, Harada T, Nakamura K, Iwasawa S, Shimokawa T, Kiura K, Yamashita N, Okamoto H.
  • Organizer: ESMO Asia Annual Meeting
  • Int'l Joint Research
• [Presentation] Phase Ib trial of nivolumab combined with metformin for refractory/recurrent solid tumors. (2018)
  • Author(s): Kubo T, Hotta K, Ninomiya T, Kato H, Horiguchi S, Takamoto A, Kozuki T, Nogami N, Ishii H, Nishina T, Harada D, Toyooka S, Okada H, Fujiwara T, Udono H, Kiura K
  • Organizer: ASCO Annual Meeting
  • Int'l Joint Research
• [Presentation] Immune checkpoint inhibitor efficacy and safety in elderly non-small cell lung cancer patients. (2018)
  • Author(s): Kubo T, Watanabe H, Ninomiya K, Kudo K, Minami D, Murakami D, Ochi N, Ninomiya T, Harada D, Yasugi M, Ichihara E, Ohashi K, Fujiwara K, Hotta K, Tabata M, Maeda Y, Kiura K
  • Organizer: ESMO Annual Meeting
  • Int'l Joint Research