464OInduction gefitinib followed by standard chemoradiotherapy in locally advanced (LA) non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutations: The LOGIK0902/OLCSG0905 intergroup phase II study

Abstract Background The standard of care for LA-NSCLC is a definitive concurrent chemoradiotherapy (CRT). In addition, durvalumab shows significant survival benefit as a consolidation therapy. However, the role of EGFR tyrosine kinase inhibitors (TKIs) in this setting has not been established, despite their efficacy in metastatic disease. The aim of this prospective phase II trial was to evaluate the efficacy and safety of induction gefitinib followed by CRT in EGFR-mutant LA-NSCLC. Methods Patients with unresectable stage III NSCLC harboring activating EGFR mutations received induction gefitinib monotherapy (250 mg/body) for 8 weeks. Patients whose disease had not progressed during induction therapy received cisplatin (40 mg/m2) and docetaxel (40 mg/m2) on days 1, 8, 29, and 36, and concurrent radiotherapy with a total dose of 60 Gy. The primary endpoint was 2-year overall survival (OS) rate. We assumed an expected 2-year OS rate of 85%; a rate of 60% was the threshold of the lower limit. Results Between 2011 and 2017, 20 patients (median age, 65.5 years; male/ female, 9/11; histology, all adenocarcinoma; stage IIIA/IIIB, 9/11; exon 19 / 21 mutations, 10/10) were enrolled. The overall response rate was 75.0% in the induction phase and 85.0% in the entire phase. The 1 and 2-year progression-free survival rates were 58.1% and 36.9%, respectively. The 2-year OS rate was 90% (95% confidence interval, 65.6-97.4), indicating this trial met the primary objective. Grade (Gr) 3 or worse adverse events (>10%) in the induction phase included transient AST elevation (25%) and ALT elevation (45%), and those in the CRT phase included neutropenia (64.7%) and febrile neutropenia (10.8%). In the 6-month follow-up period after completion of CRT, Gr > 2 radiation pneumonitis occurred in 11.8% of patients. The completion rate of the protocol therapy was 80%. No treatment-related death was observed. Conclusions This is the first prospective study to show favorable efficacy and tolerable safety of induction EGFR-TKIs in addition to standard CRT in EGFR-mutant LA-NSCLC. Further confirmatory research is warranted. Clinical trial identification UMIN000005086: 15/Feb/2011 jRCTs071180036: March/2019. Legal entity responsible for the study The authors. Funding LOGIK (Lung Oncology Group In Kyushu, Japan). Disclosure S. Saeki: Research grant / Funding (institution): Pfizer; Honoraria (institution): ONO; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Takeda. K. Hotta: Honoraria (self), Research grant / Funding (self), Relevant financial activities OUTSIDE the submitted work.: AstraZeneca; Honoraria (self), Relevant financial activities OUTSIDE the submitted work.: Nippon Kayaku. M. Yamaguchi: Honoraria (self): AstraZeneca; Honoraria (self): Daiichi Sankyo; Honoraria (self): Eli Lilly; Honoraria (self): Taiho. D. Harada: Honoraria (self), Relevant financial activities OUTSIDE the submitted work.: Chugai; Honoraria (self), Relevant financial activities OUTSIDE the submitted work.: MSD; Honoraria (self), Relevant financial activities OUTSIDE the submitted work.: Kyowa Hakko; Honoraria (self), Relevant financial activities OUTSIDE the submitted work.: ONO; Honoraria (self), Relevant financial activities OUTSIDE the submitted work.: Bristol-Myers Squibb; Honoraria (self), Relevant financial activities OUTSIDE the submitted work.: Eli Lilly; Honoraria (self), Relevant financial activities OUTSIDE the submitted work.: TAIHO; Honoraria (self), Relevant financial activities OUTSIDE the submitted work.: Boehringer Ingelheim; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution), Relevant financial activities OUTSIDE the submitted work.: AstraZeneca; Research grant / Funding (self), Relevant financial activities OUTSIDE the submitted work.: Novartis; Research grant / Funding (self), Relevant financial activities OUTSIDE the submitted work.: Kissei ; Research grant / Funding (self), Relevant financial activities OUTSIDE the submitted work.: Takeda. A. Bessho: Honoraria (self), Research grant / Funding (institution): AstraZeneca. K. Tanaka: Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution): Chugai; Honoraria (self), Honoraria (institution): AstraZeneca; Honoraria (self), Honoraria (institution): Taiho; Honoraria (self), Honoraria (institution): Pfizer; Honoraria (self), Honoraria (institution): MSD; Honoraria (self), Honoraria (institution): Eli Lilly; Honoraria (self), Honoraria (institution): Bristol-Myers Squibb; Honoraria (self), Honoraria (institution): Novartis; Honoraria (self), Honoraria (institution): Kyowa-Kirin; Honoraria (self), Honoraria (institution): AbbVie; Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution): ONO; Honoraria (institution): Daichi-Sankyo; Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution): Boehringer Ingelheim. K. Inoue: Honoraria (self): AstraZeneca. E. Ichihara: Honoraria (self): AstraZeneca; Research grant / Funding (institution): Eli Lilly. T. Sasaki: Honoraria (self): AstraZeneca. Y. Shioyama: Full / Part-time employment: FUJIFILM Corporation/FUJIFILM Medical Co., Ltd. K. Katsui: Full / Part-time employment: Tsuyama Chuo Hospital. J. Sasaki: Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Chugai; Honoraria (self): MSD; Honoraria (self): Daiichi Sankyo; Honoraria (self): Shionogi; Honoraria (self), Research grant / Funding (self): Taiho; Honoraria (self): Kyowa Kirin; Honoraria (self), Research grant / Funding (self): ONO; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (self): Yakult. K. Kiura: Honoraria (self): AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (self): Taiho; Honoraria (self), Research grant / Funding (self): Chugai; Honoraria (self), Research grant / Funding (self): Pfizer; Honoraria (self), Research grant / Funding (self): ONO; Honoraria (self), Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (self): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (self): Daiichi Sankyo; Research grant / Funding (self): Kyorin; Research grant / Funding (self): Nippon Kayaku. K. Sugio: Research grant / Funding (institution): MSD. All other authors have declared no conflicts of interest.