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

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.