401P - A prospective, phase II trial of low-dose afatinib monotherapy for patients with EGFR, mutation-positive, non-small cell lung cancer (TORG1632)

Background

Afatinib is an efiective 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 eficacy 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-ofi 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 were 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 in plasma and tissues. 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 eficacy and good tolerability.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Thoracic Oncology Research Group.

Funding

Has not received any funding.

Disclosure

K. Kubota: Honoraria (self): Chugai Pharmaceutical, Taiho Pharmaceutical, MSD, Nippon Boehringer Ingelheim, Bristol-Myers Squibb, kyowa-hakko Kirin, AstraZeneca, Ono Pharmaceutical; Research grant/Funding (institution): Ono Pharmaceutical, Nippon Boehringer Ingelheim. K. Naoki: Speaker Bureau/Expert testimony: Nippon Boehringer Ingelheim; Research grant/Funding (institution): Nippon Boehringer Ingelheim; Spouse/Financial dependant: Nippon Boehringer Ingelheim. A. Bessho: Honoraria (self): Nippon Boehringer Ingelheim. K. Minato: Research grant/Funding (institution): Taiho Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb. N. Seki: Honoraria (self): AstraZeneca, Nipppon Boehringer Ingelheim, Eli Lilly Japan, Daiichi Sankyo, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Taiho Pharmaceutical, Chugai Pharmaceutical; Research grant/Funding (self): Nihon Medi-Physics, Nippon Boehringer Ingelheim; Research grant/Funding (institution): AstraZeneca. T. Tokito: Honoraria (self): AstraZeneca, Chugai Pharmaceutical, MSD. N. Furuya: Honoraria (self): Eli Lilly Japan, Chugai Pharmaceutical, AstraZeneca, Bristol-Myers Squibb, Taiho Pharmaceutical, NipponBoehringer Ingelheim. H. Hayashi: Research grant/Funding (institution): Nippn Boehringer Ingelheim. H. Iihara: Research grant/Funding (institution): 19 飯原 大稔 附随研究 \"岐阜薬科大学 岐阜大学医学部附属病院” Nippon Boehringer Ingelheim. H. Okamoto: Research grant/Funding (institution): Takeda, MSD, Ono Pharmaceutical, AstraZeneca, Merck, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol-Myers Squibb, Eli Lilly Japan, Daiich Sankyo. All other authors have declared no conflicts of interest.