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

Background In a phase I study, Afa (30 mg/body daily) plus Bev (15 mg/kg every 3 weeks) was well tolerated and had evidence of favorable disease control (Lung Cancer, 2018). We report an updated progression free survival (PFS), overall survival (OS) and tolerability analysis. Methods At first, pts received Afa at 40 mg/body daily and Bev intravenously at 15 mg/kg every 3 weeks (level 0) until progression of disease (PD) or occurrence of unacceptable toxicity and next, pts received Afa at 30 mg/body daily and Bev intravenously at 15 mg/kg every 3 weeks (level -1). The primary endpoint was set as rate of dose limiting toxicities. PFS, OS and tolerability of long term treatment were important key secondary end points. The cumulative survival rate will be estimated by the Kaplan-Meier method. Results Nineteen pts were enrolled (level 0: 5 and level -1: 14). At data cutoff (Oct 1, 2018; median follow-up, 27.4 months), 7 pts continued the treatment, 5 pts discontinued the treatment for progression of the lung cancer and 7 pts discontinued the treatment for toxicities (4 pts) or pts’ wish (3 pts). Median PFS was 23.4 months (95% CI: 17.7 months to not reached). In terms of OS, only two events have happened and median OS was not reached. Adverse events (AEs) happened in all pts. Severe AEs were shown in the table. Among 16 evaluable pts, the best response was PR (88%) and disease control rate was 100%. T790M were detected in two pts (a patient whose Afa was discontinued by progression and a patient after gefitinib whose Afa was discontinued by toxicities). Osimertinib were administered to these two pts. Table . 1525P N = 19 Grade 4 AE 0 Grade 3 AE 15 Grade 3 Diarrhea 4 Skin rash 4 Hypoxia 1 Stomatitis 1 Paronychia 1 Neutrpenia 1 Anorexia 1 Proteinuria 1 Hypertension 1 Conclusions This is the first report that PFS and OS of Afa plus Bev treatment were monitored for long term in chemo-naive pts. With prolonged follow-up, first-line Afa plus Bev has very long PFS and OS. This therapy appears promising and we are doing a subsequent randomized trial (Afa plus Bev vs Afa alone, jRCTs061180006). Clinical trial identification UMI15944. Release date 16/Dec/2014. Legal entity responsible for the study Okayama Lung Cancer Study Group. Funding Has not received any funding. Disclosure T. Ninomiya: Honoraria (self): Chugai Pharmaceutical Co.; Honoraria (self), Research grant / Funding (institution): Nippon Boehringer Ingerheim Co. N. Nogami: Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Pfizer; Honoraria (self): BMS; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Eli Lilly; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Ono Pharmaceutical. T. Kozuki: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Nippon Boehringer Ingerheim Co.; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical; Honoraria (self): Kyowa-Hakko Kirin; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan; Honoraria (self), Research grant / Funding (institution): Merck Biopharma; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Pfizer; Honoraria (self): Taiho Pharmaceutical. D. Harada: Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): AstraZeneca; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): Eli Lilly Japan; Honoraria (self): MSD KK. T. Kubo: Honoraria (self), Research grant / Funding (self): BMS; Honoraria (self): Taiho; Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Ono Pharmaceutical; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Kyowa Hakko Kirin. K. Ohashi: Research grant / Funding (self): Nippon Boehringer Ingelheim; Research grant / Funding (self): Novartis. S. Kuyama: Honoraria (self): AstraZeneca; Honoraria (self): Meiji Seika Pharma; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Kyorin Pharma; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Novartis; Honoraria (self): BMS; Honoraria (self): Eli Lilly Japan. A. Bessho: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Chugai Pharma; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb Japan; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Novartis; Honoraria (self): Eli Lilly Japan; Honoraria (self): Daiichi Sankyo; Honoraria (self), Research grant / Funding (institution): Kyorin; Research grant / Funding (institution): AbbVie. N. Fujimoto: Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Hisamitsu Pharmaceutical; Honoraria (self): Eli Lilly Japan; Honoraria (self): Daiichi Sankyo; Honoraria (self): Astellas Pharma Inc. K. Aoe: Advisory / Consultancy: Boehlinger Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Ono Pharmaceutical; Speaker Bureau / Expert testimony, Research grant / Funding (self): BMS; Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Novartis. T. Shibayama: Honoraria (self): Ono Pharmaceutical; Honoraria (self): MSD KK; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Novartis; Honoraria (self): AstraZeneca. N. Ochi: Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Chugai Pharmaceutical. N. Takigawa: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Daiichi-Sankyo Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Kyowa Hakko Kirin; Research grant / Funding (institution): Nippon Kayaku. K. Hotta: Honoraria (self), Research grant / Funding (self): Chugai Pharmaceutical; Honoraria (self): Nippon Boehringer Ingerheim Co. K. Kiura: Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Ono Pharmaceutical; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Pfizer Japan; Honoraria (self): Eli Lilly Japan; Honoraria (self): MSD; Honoraria (self): Daiichi Sankyo; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (self): Boehringer Ingelheim. All other authors have declared no conflicts of interest.