The safety assessment of crizotinib and alectinib from real-world data of 840 ALK-inhibitor naïve patients with NSCLC harboring ALK-rearrangement (WJOG9516L)

Abstract

Abstract Background Previous clinical trials demonstrated that alectinib (ALEC) produced fewer adverse events compared to crizotinib (CRZ). Data regarding adverse events (AE) in clinical practice, however, is limited. We reviewed ALK-rearranged NSCLC patients treated with crizotinib or alectinib in institutions of the West Japan Oncology Group, and the safety of CRZ and ALEC were evaluated using the real-world data. Methods We reviewed the clinical data of ALK-rearranged NSCLC patients who received CRZ or ALEC between May 2012 and Dec 2016. Patients were divided into two groups, the CRZ, or the ALEC group. To evaluate the safety of each ALK-inhibitor, we compared the AEs between the CRZ and the ALEC groups. Results Of 864 patients enrolled from 61 institutions, 840 patients were analyzed. Median age was 61 (range, 20-94); 56% were female; and 95% had adenocarcinoma. There was no significant difference in the frequencies of ILD, renal dysfunction, and digestive dysfunction between the CRZ and the ALEC groups.(p\xa0=\xa00.905, p\xa0=\xa00.7208, p\xa0=\xa00.1735) Meanwhile, liver dysfunction was significantly more frequent in the CRZ group compared to the ALEC group.(50.7% in CRZ group vs. 29.1% in ALEC group, p\xa0=\xa00.0313) In adverse events of grade 3 or more, liver dysfunction remained significantly different in frequency between the two groups.(13.3% in CRZ vs. 3.9% in ALEC, p\xa0 Conclusions In clinical practice, the patients treated with CRZ exhibited a trend to discontinue CRZ at a higher rate due to AE compared to the ALEC group. The PFS of patients treated with ALEC, even in the patients who experience AE due to CRZ, was more than 2 years. Clinical trial identification UMIN000028605. Legal entity responsible for the study Nobuyuki Yamamoto. Funding Pfizer. Disclosure K. Ito: Honoraria (self): Pfizer; Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim; Speaker Bureau / Expert testimony: Chugai; Honoraria (self): Eli Lilly; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Kyorin; Research grant / Funding (institution): Daiichi-Sankyo. T. Yamanaka: Honoraria (self), Research grant / Funding (self): Takeda; Honoraria (self): Chugai; Honoraria (self), Research grant / Funding (self): Taiho; Honoraria (self): Boehringer Ingelheim; Advisory / Consultancy: Giiead Sciences; Advisory / Consultancy: Bayer. D. Fujimoto: Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Taiho Pharmaceutical Co; Honoraria (self): Chugai Pharmaceutical Co; Honoraria (self): MSD KK; Honoraria (self): Boehringer Ingelheim Japan Inc; Honoraria (self): Eli Lilly Japan KK,. M. Mori: Honoraria (institution), Speaker Bureau / Expert testimony: Chugai. H. Tanaka: Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (institution): Eli Lilly; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Taiho pharmaceuticals; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (institution): Ono pharmaceuticals; Honoraria (self), Research grant / Funding (institution): Chugai pharmaceuticals; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Takeda pharmaceuticals; Research grant / Funding (institution): Merck Serono. S. Teraoka: Honoraria (self): Chugai Pharmaceutical. O. Hataji: Honoraria (self): Chugai; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Boerhringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Daiichi-Sankyo; Honoraria (self), Research grant / Funding (institution): Kyorin; Honoraria (self): Eli Lilly. A. Bessho: Honoraria (self), Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer Japan Inc. A. Kubo: Honoraria (self), Research grant / Funding (self): Boehringer Ingerheim; Honoraria (self), Research grant / Funding (self): Chugai; Honoraria (self), Research grant / Funding (self): Eli Lilly; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Ono Pharma. K. Nakagawa: Honoraria (self), Advisory / Consultancy: Astellas Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda Pharmaceutical; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Eli Lilly; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self), Research grant / Funding (institution): Novartis Pharma; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Pfizer Japan; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Company; Honoraria (self): KYORIN Pharmaceutical; Honoraria (self): MEDICUS SHUPPAN,Publishers; Honoraria (self): Thermo Fisher Scientific K.K; Honoraria (self): Nichi-Iko Pharmaceutical ; Honoraria (self): Hisamitsu Pharmaceutical; Research grant / Funding (institution): Eisai Co; Research grant / Funding (institution): PAREXEL International Corp. N. Yamamoto: Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Chugai. All other authors have declared no conflicts of interest.