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Phase II study of afatinib for advanced non-small cell lung cancer with uncommon epidermal growth factor receptor
Nobuaki Mamesaya1, Keita Mori2, Haruki Kobayashi1
1Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
Background:
There are no prospective clinical data on the efficacy of afatinib in patients with non-small cell lung cancer (NSCLC) harboring various uncommon epidermal growth factor receptor (EGFR) mutations detected using next-generation sequencing. We aimed to report the efficacy and safety of afatinib in patients with NSCLC harboring uncommon EGFR mutations detected using next-generation sequencing.
Methods:
This was a prospective single-center single-arm phase II study. Patients with histologically confirmed metastatic or recurrent NSCLC harboring uncommon EGFR mutations, excluding exon 20 insertion and T790M mutations detected using next-generation sequencing, were eligible. Patients received oral afatinib (40 mg once daily). The primary endpoint was the objective response rate. The secondary endpoints were progression-free survival, overall survival, and safety.
Results:
Between August 2019 and September 2022, 17 patients were enrolled. The median age was 71 years (range, 59-80 years; 9 males). The uncommon mutations identified were G719X (n = 4; 24%), S768I (n = 3; 17.6%), and L861Q (n = 6; 35%), and 13 other rare EGFR mutations were detected in 10 patients. These mutations were identified as single or compound mutations. The objective response rate for all patients was 82.4%, median progression-free survival was 11.3 months, and median overall survival was 27.8 months. Grade 3 or higher adverse events were diarrhea (n = 5; 29%), paronychia (n = 2; 12%), and decreased appetite (n = 2; 12%). All adverse events were manageable, and there were no treatment-related deaths.
Conclusions:
Afatinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring uncommon EGFR mutations.
Insights
Afatinib shows promising efficacy in non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. This study highlights its manageable safety profile for this specific patient group.
Area of Science:
- Oncology
- Medical Genetics
- Clinical Pharmacology
Background:
- Limited prospective data exist on afatinib's efficacy in non-small cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations.
- Next-generation sequencing (NGS) enables detection of diverse EGFR mutations, necessitating clinical evaluation of targeted therapies.
Purpose of the Study:
- To evaluate the efficacy and safety of afatinib in NSCLC patients with uncommon EGFR mutations identified by NGS.
- To provide prospective clinical data for a patient subgroup often excluded from clinical trials.
Main Methods:
- A prospective, single-center, single-arm Phase II clinical study.
- Inclusion criteria: metastatic or recurrent NSCLC with uncommon EGFR mutations (excluding exon 20 insertion and T790M) detected by NGS.
- Treatment: Oral afatinib 40 mg once daily; primary endpoint: objective response rate (ORR).
Main Results:
- Seventeen patients were enrolled, with a median age of 71 years.
- Common mutations included G719X, S768I, and L861Q, alongside other rare EGFR mutations.
- Observed ORR of 82.4%, median progression-free survival (PFS) of 11.3 months, and median overall survival (OS) of 27.8 months.
Conclusions:
- Afatinib demonstrated significant anti-tumor activity in NSCLC patients with uncommon EGFR mutations.
- The treatment exhibited a manageable safety profile, with common adverse events including diarrhea and paronychia.
- Afatinib represents a viable therapeutic option for NSCLC patients harboring these specific genetic alterations.
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