Patients treated with afatinib for EGFR-mutated (EGFRm) non–small-cell lung cancer (NSCLC) often require treatment modifications because of drug toxicities. This study aimed to evaluate the safety and efficacy of a lower dosage of afatinib in patients with EGFRm NSCLC.
The trial to assess a lower dose of afatinib was a multicenter, single-arm, open-label phase 2 study. A 20-mg daily dose of afatinib was given to treatment-naïve patients with advanced NSCLC and common EGFR mutations. The dosage of afatinib was maintained unless tumor growth occurred. Progression-free survival (PFS) was monitored as a primary end point, with a threshold median PFS of 9.2 months and an expected median PFS of 13.8 months.
Fifty-three patients from 21 institutions throughout Japan were enrolled in the trial between March 2017 and September 2018. Of the patients, 28 were women and the median age was 70 years (range, 37-85 years). The most common EGFR mutations included in the study were exon 19 deletion (56.6%) and L858R point mutation (43.4%). Most patients enrolled in the study had a performance status of 0 or 1 (86.8%).
The median follow-up was 20.8 months as of the March 2020 cutoff date. The study results included a median PFS of 12.6 months (95% confidence interval [CI], 9.7-14.3), a median time to treatment failure of 18.6 months (95% CI, 16.0-21.2), and overall survival not reached. The objective response rate was 66.6% (95% CI, 51.7-78.5), and the disease control rate was 92.5% (95% CI, 81.8-97.9). Twelve (22.6%) patients had a grade ≥3 adverse event, with 4 (7.5%) of the patients having diarrhea. This percentage of patients with diarrhea was lower than seen in phase 3 trials in which patients were receiving afatinib 40 mg daily. Eight patients from a group of 19 had an EGFR T790M resistance mutation. No correlation was found between afatinib plasma concentrations after 9 days and clinical outcomes or adverse events.
The authors concluded that, based on the study results, a low dose of afatinib should be considered as a possible standard therapy when treating patients with EGFRm NSCLC.
Noro R, et al. ESMO 2020. Abstract 1365P.