What question did this study set out to answer?

This research aims to evaluate the efficacy and safety of afatinib for patients with EGFR-mutated non-small cell lung cancer who have previously been treated with osimertinib.

May 30, 2026

A multicenter pilot study of afatinib re-challenge in patients with EGFR -mutated non-squamous non–small cell lung cancer previously treated with osimertinib.

Key Points

This research aims to evaluate the efficacy and safety of afatinib for patients with EGFR-mutated non-small cell lung cancer who have previously been treated with osimertinib.
Multicenter, single-arm, phase II study enrolling patients with advanced/recurrent EGFR-mutated non-small cell lung cancer.
Patients underwent genomic profiling after progression on osimertinib.
Primary endpoint was objective response rate, with secondary endpoints including progression-free survival and overall survival.
Of 17 evaluable patients, the objective response rate was 11.8% (95% CI: 1.5-36.4).
Median progression-free survival was 4.5 months (95% CI: 2.9-9.2), and median overall survival was 20.8 months (95% CI: 9.0-NA).
Adverse events occurred in 88.2% of patients, with Grade 3 adverse events in 29.4%, primarily manageable diarrhea.

Abstract

e20748 Background: Osimertinib (+ chemotherapy) is the standard first-line treatment for EGFR -mutated non-squamous non-small cell lung cancer (NSqNSCLC). However, evidence regarding the efficacy of EGFR-TKI re-challenge after progression on osimertinib remains insufficient. This study evaluated the efficacy and safety of afatinib as a subsequent therapy following progression on osimertinib and conventional chemotherapy. Methods: This multicenter, single-arm, phase II study enrolled patients (pts) with advanced/recurrent EGFR -mutated (del19 or L858R) NSqNSCLC and an ECOG PS 0–1. All pts underwent NGS-based comprehensive genomic profiling (CGP) after progressing on osimertinib. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: Between Oct 2022 and Dec 2024, 19 pts were enrolled. Due to slow accrual, the study was terminated before reaching the planned sample size. Of 17 evaluable pts, the ORR was 11.8% (95% CI: 1.5-36.4), mPFS was 4.5 mos. (95% CI: 2.9-9.2), and mOS was 20.8 mos. (95% CI: 9.0-NA). CGP identified several biomarkers potentially involved in osimertinib resistance, including EGFR C797S (n = 1), ERBB2 mutation (n = 1), PIK3CA mutation (n = 1), RET mutation (n = 1), and METex14 skipping (n = 1); however, no clear correlation between these markers and afatinib efficacy was observed. Any-grade adverse events (AEs) occurred in 88.2% of pts, with Grade 3 AEs in 29.4% (5/17), primarily diarrhea, which were manageable with dose interruptions or reductions. Conclusions: Afatinib re-challenge showed limited efficacy in pts with EGFR -mutated NSqNSCLC pretreated with osimertinib and chemotherapy. While the safety profile was consistent with previous reports, these findings suggest that alternative therapeutic strategies should be prioritized in this clinical setting. (UMIN000049225). Clinical trial information: UMIN000049225 .

KI fragen

Bookmark

Cite This Study

Araki et al. (Thu,) studied this question.

synapsesocial.com/papers/6a1a82b80307b7850943459b https://doi.org/https://doi.org/10.1200/jco.2026.44.16_suppl.e20748

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

KI fragen

Bookmark