A multicenter single-arm phase II study of nab-paclitaxel/carboplatin for non-small cell lung cancer patients with interstitial lung disease

Background: The prognosis of non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) has been reported to be poor, and 10-20% of those receiving chemotherapy experienced exacerbation of ILD induced by chemotherapy. To evaluate the safety and efficacy of nab-paclitaxel (nab-P)/ carboplatin (C) for NSCLC patients with ILD, this multicenter phase II study was conducted. Methods: Chemotherapy-naive patients with pathologically confirmed advanced NSCLC and ILD received 4 cycles of nab-P (100 mg/m2, d1, 8, 15) + C (AUC=6 d1) every 3 weeks. ILDs were diagnosed based on the fibrosing ILD criteria and categorized to three patterns by investigators; usual interstitial pneumonia (UIP), possible UIP, inconsistent UIP. Primary endpoint was exacerbation-free rate (EFR) of ILD at 28 days after protocol treatment. Secondary endpoints were response rate, progression-free survival (PFS), overall survival (OS), EFR of ILD, toxicities. Results: From 06/2014 to 12/2016, 94 patients were enrolled in this study, and 92 patients received protocol treatment. Median age was 70 years, 89% were male, 45/55% were PS 0/1, and 58% had non-squamous histology. In the primary analysis, EFR of ILD at 28 days after protocol treatment was 95.7% (88/92, 90%CI; 90.3-98.6). In the subgroup of patients with UIP pattern, EFR of ILD at 28 days was 94% (47/50). Response rate was 51% (90%CI; 40-62). At the time of data cutoff, median PFS was 6.1 months, and median OS was 15.1 months. The most common grade 3 or 4 adverse events were neutropenia (75%), leukopenia (53%), anemia (48%), thrombocytopenia (20%), hyponatremia (17%), febrile neutropenia (9%) and infection (7%). Two treatment-related deaths (one each of pulmonary infection and ILD exacerbation) were observed. Conclusions: This study demonstrated that nab-P/C was well tolerated in NSCLC patients with ILD in terms of safety including risk of exacerbation of ILD, even if of UIP pattern. Although this study was a single arm, nab-P/C might be more effective compared with other regimens of previous reports. Legal entity responsible for the study: Kanagawa Cardiovascular and Respiratory Center. Funding: Japanese Ministry of Health, Labor and Welfare. Disclosure: H. Kenmotsu: Grants and Honoraria: AstraZeneca K.K., Chugai Pharmaceutical Co, Ltd., Boeringer Ingelheim, Ono Pharmaceutical Co, Ltd., Bristol-Myers K.K, Eli Lilly K.K, Kyowa Hakko Kirin Co., Ltd., MSD K.K., Novartis Pharma K.K. K. Yoh: Research funding and honoraria: Taiho Pharmaceutical. T. Baba: Honoraria: Ono Pharmaceutical Co, Ltd, Bristol Myers Squibb K.K., AstraZeneca K.K., Toray Industries, INC, Daiichi Sankyo, Inc.; Speakers' bureau: AstraZeneca K.K., Boston Scientific Japan Co.,Ltd., Nippon Boehringer Ingelheim Co., Shionogi & Co., Ltd., Astellas Pharma Inc, Amco Inc., Asahi Kasei Pharma Corporation; Research funding: Taiho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Savara Inc., Hisamitsu Pharmaceutical Co., Inc., AstraZeneca K.K. Y. Fujiwara: Grants: AbbVie, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Incyte, Merck Serono, Novartis grants; Personal fees: AstraZeneca, MSD, BMS, personal fees from Taiho, Ono, outside the submitted work. O. Yamaguchi: Honoraria: Bristol-Myers Squibb, Ono Pharmaceutical, AstraZeneca. H. Okamoto: Takeda, MSD, Ono, AstraZeneca, Merck, Chugai, Taiho, Bristol, Eli Lilly, Daiichi Sankyo. N. Yamamoto: Membership of advisory board: AstraZeneca, Boehringer-Ingelheim, Chugai, Eli Lilly, MSD, Takeda; Corporate-sponsored research: MSD, Eli Lilly, Chugai; Honoraria: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Ono Pharmaceutcial Ltd., Pfizer, Takeda. T. Ninomiya: Honoraria: Chugai Pharmaceutical Co., Nippon Boehringer Ingerheim Co. T. Ogura: Advisory board: Nippon Boehringer Ingelheim Co., Shionogi & Co., Ltd; Speakers' bureau: Nippon Boehringer Ingelheim Co., Shionogi & Co., Ltd., Astellas Pharma Inc.; Research funding: Taiho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co, Savara Inc, Hisamitsu Pharmaceutical Co., Inc., AstraZeneca K.K. T. Kato: Honoraria and Research grant: Bristol Myers Squibb and Taiho. All other authors have declared no conflicts of interest.