Abstract 1365P
Background
Afatinib is an effective treatment for patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC), however, its toxicities often require dose modifications. The aim of this study was to assess the efficacy and safety of low dose afatinib monotherapy in patients with EGFR mutation-positive NSCLC.
Methods
This study was a multicenter, single-arm, open-label phase II trial. Treatment-naïve patients with advanced NSCLC positive for common EGFR mutations received afatinib in a dose of 20mg/day. The same dose was continued unless the tumor had grown. The primary endpoint (PE) was progression-free survival (PFS) The threshold median PFS was 9.2 months and the expected median PFS 13.8 months.
Results
From March 2017 through September 2018, 53 patients were enrolled from 21 institutions in Japan. The median age was 70 years (range, 37–85), and 28 patients (52.8%) were women. EGFR mutation subtypes included exon 19 deletion (56.6%) and L858R point mutation (43.4%). Most patients had a performance status of 0 or 1 (86.8%). As of the data cut-off date of March 2020, the median follow-up was 20.8 months. The median PFS, time to treatment failure and overall survival were 12.6 months (95% CI: 9.7–14.3), 18.6 months (95%CI: 16.0-21.2) and not reached. The PE was met. The objective response and the disease control was 66.6% (95% CI: 51.7-78.5) and 92.5% (95% CI: 81.8-97.9). Adverse events (AEs) of grade 3 or higher occurred in 12 patients (22.6%) including diarrhea in 4 patients (7.5%) that was lower than that observed in phase III studies of afatinib using 40 mg. Eight of 19 patients (42.1%) had T790M resistant mutation. Afatinib plasma concentrations at 9 days after the start of administration had no correlations with clinical outcomes and AEs including diarrhea.
Conclusions
Low dose afatinib would be considered as one of standard therapy for EGFR mutation-positive NSCLCs because of promising clinical efficacy and good tolerability.
Clinical trial identification
UMIN000027338.
Editorial acknowledgement
Legal entity responsible for the study
Thoracic Oncology Research GroupTORG.
Funding
Nippon Boehringer Ingelheim, TORG, NBI.
Disclosure
R. Noro: Honoraria (self): Boehringer Ingelheim; Honoraria (self): AstraZeneca. A. Bessho: Honoraria (self): Boehringer Ingelheim. N. Seki: Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Lilly Japan; Honoraria (self): Daiichi Sankyo; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): MSD Oncology; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Chugai Pharma; Research grant/Funding (self): Nihon Medi-Physics; Research grant/Funding (self): Boehringer Ingelheim; Honoraria (institution): AstraZeneca. T. Tokito: Honoraria (self): AstraZeneca; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): MSD. N. Furuya: Honoraria (self): Eli Lilly; Honoraria (self): Chugai; Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Taiho; Honoraria (self): Boehringer Ingelheim. K. Naoki: Speaker Bureau/Expert testimony: Nippon Boehringer Ingelheim Co., Ltd.; Research grant/Funding (institution): Nippon Boehringer Ingelheim Co., Ltd. H. Okamoto: Honoraria (institution): Takeda; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Ono; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Bristol; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Daiichi Sankyo. K. Kubota: Honoraria (self): Chugai; Honoraria (self): Taiho; Honoraria (self): MSD; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): Bristol-Myers; Honoraria (self): Squibb; Honoraria (self): Kyowa-Hakko Kirin; Honoraria (self): AstraZeneca; Honoraria (self): Ono; Research grant/Funding (institution): Ono; Research grant/Funding (institution): Nippon Boehringer Ingelheim. All other authors have declared no conflicts of interest.