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Updated: Jul 8, 2026

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

Afatinib for Advanced Cancers Carrying an EGFR, HER2, or HER3 Mutation: An Open-Label, Phase II, Belgian Precision

Lore Decoster1, Philippe Aftimos2, Sylvie Rottey3

  • 1Department of Medical Oncology, Laboratory for Medical and Molecular Oncology (LMMO), Vrije Universiteit Brussel (VUB), Translational Oncology Research Center (TORC), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium.

JCO Precision Oncology
|July 6, 2026
PubMed
Abstract

Insights

Afatinib showed limited efficacy in HER2-mutated solid tumors but demonstrated clinical responses in some EGFR-mutated patients. Further HER-targeting research in solid tumors is recommended.

Area of Science:

  • Oncology
  • Genomics
  • Pharmacology

Background:

  • The Belgian Precision initiative promotes tumor-agnostic next-generation sequencing (NGS) for advanced cancer.
  • Expanding access to genotype-matched therapies is crucial for personalized cancer treatment.

Purpose of the Study:

  • To evaluate the efficacy of afatinib in patients with advanced solid tumors harboring activating HER2, EGFR, or HER3 mutations.
  • To assess afatinib's effectiveness in a tumor-agnostic setting based on specific genetic alterations.

Main Methods:

  • An open-label, phase II trial with three cohorts: HER2-, EGFR-, and HER3-mutated solid tumors.
  • Utilized a Simon two-stage design to determine objective response rate (ORR) as the primary endpoint.
  • Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival, overall survival, and safety.

Main Results:

  • A total of 45 patients were enrolled. The HER2 cohort (n=30) showed an ORR of 3.3% and DCR of 23.3%.
  • The EGFR cohort (n=7) achieved an ORR of 28.6% with responses lasting 6.6 and 15.4 months.
  • The HER3 cohort (n=8) had no objective responses. Afatinib's safety profile was consistent with known data.

Conclusions:

  • The study did not meet its primary endpoint in the HER2-mutated cohort.
  • While EGFR and HER3 cohorts were not fully accrued, meaningful responses were seen in two EGFR-mutated patients.
  • Further investigation into HER-targeting therapies for solid tumors is warranted.

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