PhaseIIStudy ofLow-DoseAfatinib Maintenance Treatment Among Patients withEGFR-Mutated Non-SmallCell Lung Cancer: North Japan Lung Cancer Study Group Trial 1601 (NJLCG1601)

Lessons Learned Low-dose afatinib maintenance treatment among patients withEGFR-mutated NSCLC achieved long-time to treatment failure with fewer treatment-related AEs without detracting from the therapeutic efficacy. This modified regimen represents a practical usage that balances effectiveness and safety. Background Although afatinib is an effective therapy for patients withEGFR-mutated non-small cell lung cancer (NSCLC), drug-related adverse events (AEs) have often necessitated dose reductions. In a post hoc analysis of the LUX-Lung 3 and 6 trials, there was no difference in median progression-free survival (PFS) between patients who had the dose of afatinib reduced and those who did not. We thus evaluated the efficacy and tolerability of low-dose afatinib maintenance treatment among patients with NSCLC harboringEGFRmutations who had not been previously treated. Methods Eligible patients received afatinib 40 mg orally once daily. When prescribed grade >= 2 AEs, rash of grade >= 3, or unacceptable toxicity occurred, the afatinib dose was reduced from 40 to 30 mg and if needed from 30 to 20 mg. The primary endpoint was the 1-year PFS rate. Secondary endpoints were PFS, overall response rate (ORR), and toxicity. Results Among 30 patients, 93% had adenocarcinoma, 53% had exon 19 deletion, 37% had L858R, and 10% had minor mutations. The 1-year PFS rate was 50% (95% confidence interval [CI], 31.3-66.1) and the median PFS was 11.8 months (95% CI, 7.1-21.4). The incidence rate of grade >= 3 toxicities was 57%, including elevated aspartate aminotransferase/alanine aminotransferase level (13%), diarrhea (10%), and paronychia (10%). Conclusion Low-dose afatinib maintenance treatment reduced treatment-related AEs without detracting from the therapeutic efficacy.