Afatinib Plus Osimertinib in the Treatment of Osimertinib-resistant Non-small Cell Lung Carcinoma: a Phase I Clinical Trial

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2023 Jan 3

PMID 36597021

Authors

Satoru Miura

Yasuhiro Koh

Koichi Azuma

Hiroshige Yoshioka

Kenichi Koyama

Shunsuke Teraoka

Hidenobu Ishii

Kayoko Kibata

Yuichi Ozawa

Takaaki Tokito

Jun Oyanagi

Toshio Shimokawa

Takayasu Kurata

Nobuyuki Yamamoto

Hiroshi Tanaka

Affiliations

Soon will be listed here.

Abstract

Background: Conquering acquired resistance to osimertinib remains a major challenge in treating patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Thus, we aimed to determine the safety and efficacy of combination treatment with osimertinib and afatinib for patients with acquired resistance to osimertinib.

Methods: This open-label phase I study was a feasibility study of the combination of afatinib and osimertinib for patients with advanced EGFR-positive NSCLC who had progressive disease after receiving osimertinib. The primary endpoint was to determine the maximum tolerated dose (MTD). We enrolled patients who received afatinib at three different dose levels (level 1, 20 mg; level 2, 30 mg; level 3, 40 mg) combined with osimertinib at a standard dose of 80 mg once per day.

Results: Thirteen patients were enrolled in this study. The MTD was defined as 30 mg afatinib when combined with daily oral administration of osimertinib (80 mg). The most frequent adverse events were diarrhea (76.9%), anemia (76.9%), and rash (69.2%). Considering the toxicity profiles during all treatment periods, the recommended oral dose of afatinib was determined as 20 mg daily, with an osimertinib dose of 80 mg. For all evaluable patients (n = 12), the response rate was 7.7% and the disease-control rate was 46.2%.

Conclusion: Combination therapy with osimertinib and afatinib was tolerable; however, the synergistic effect of afatinib with osimertinib may be limited in osimertinib-resistant patients.

Trial Registration: Japan Registry of Clinical Trials ID: jRCTs051180008, registered date: 08/11/2018.

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