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Published on: June 26, 2019
An Observational Study of Afatinib 30 mg Daily in Patients With Advanced Non-Small-Cell Lung Cancer Harboring Common
Kenneth Sooi1, Pongwut Danchaivijtr2, C K Wong3
1Department of Haematology-Oncology, National University Hospital, Singapore, Singapore.
Background:
Afatinib is an approved first-line treatment for advanced non-small-cell lung cancer (NSCLC) harboring sensitizing EGFR mutations. At the standard 40 mg dose, 28%-53% of patients in randomized trials required dose reductions due to adverse events (AEs), predominantly cutaneous and gastrointestinal. This study evaluated whether a 30 mg starting dose could improve tolerability without compromising efficacy.
Methods:
This multicenter, single-arm phase 2 study enrolled treatment-naive patients with advanced EGFR-mutant NSCLC. Patients received afatinib 30 mg daily until progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival (PFS) rate. Secondary endpoints included median PFS, time-to-treatment failure (TTF), objective response rate (ORR), disease control rate (DCR), and safety. Using A'Hern's single-stage design (one-sided α = 0.1, 80% power), 62 patients were required to distinguish a target 6-month of PFS ≥ 75% from ≤ 62%.
Results:
The study was terminated early due to slow accrual; 30 patients were enrolled between May 2023 and May 2024. Median follow-up was 11.3 months (IQR 9.6-15.5). The 6-month PFS rate was 93.2% (95% CI 75.5-98.3), median PFS of 15.8 months (95% CI 13.4-not reached) and median TTF of 17.0 months. ORR was 80% and DCR 96.7%. Common treatment-related AEs included diarrhea (83.3%), mucositis (60.0%), paronychia (60.0%), and acneiform rash (46.7%). Grade ≥ 3 AEs occurred in 10.0% of patients, with no Grade 4-5 events. Dose modification was required in 13.3% of patients.
Conclusion:
Afatinib 30 mg daily was well tolerated and demonstrated encouraging efficacy, with a 6-month PFS of 93.2%, suggesting outcomes comparable to standard dosing.
Trial Registration:
Registration number: NCT04909073; https://clinicaltrials.gov.
Insights
A lower starting dose of afatinib (30 mg) for advanced EGFR-mutant non-small-cell lung cancer (NSCLC) showed good tolerability and promising efficacy. This dose may offer a better treatment option for patients with this type of lung cancer.
Area of Science:
- Oncology
- Pharmacology
Background:
- Afatinib is a first-line treatment for advanced non-small-cell lung cancer (NSCLC) with EGFR mutations.
- Standard 40 mg afatinib dose requires reduction in 28%-53% of patients due to adverse events.
- This study investigated a 30 mg starting dose for improved tolerability and efficacy.
Purpose of the Study:
- To evaluate the efficacy and tolerability of a 30 mg daily starting dose of afatinib.
- To determine if a lower starting dose can reduce adverse events without compromising treatment outcomes.
Main Methods:
- A multicenter, single-arm phase 2 study of treatment-naive patients with advanced EGFR-mutant NSCLC.
- Patients received afatinib 30 mg daily.
- Primary endpoint: 6-month progression-free survival (PFS) rate. Secondary endpoints: median PFS, TTF, ORR, DCR, and safety.
Main Results:
- The study enrolled 30 patients; median follow-up was 11.3 months.
- 6-month PFS rate was 93.2%, median PFS 15.8 months, and median TTF 17.0 months.
- Objective response rate (ORR) was 80%, disease control rate (DCR) 96.7%. Common adverse events included diarrhea and mucositis. Grade ≥3 adverse events occurred in 10.0% of patients.
Conclusions:
- Afatinib 30 mg daily is well-tolerated and shows encouraging efficacy in advanced EGFR-mutant NSCLC.
- The 6-month PFS rate of 93.2% suggests comparable outcomes to the standard dose.
- A lower starting dose may improve patient tolerability.
