Study evaluated the benefits of afatinib in Asian and non-Asian patients who had not received EGFR-TKI therapy for their EGFR-mutant NSCLC.
Accounting for between 7% and 23% of EGFR mutation–positive non–small-cell lung cancer (NSCLC), uncommon EGFR mutations produce heterogeneous EGFR tyrosine kinase inhibitor (TKI) responses.1 Afatinib is a second-generation EGFR-TKI (ErbB family blocker) that has shown broad inhibitory activity against uncommon mutations in vitro and clinical activity against major uncommon mutations (G719X/L861Q/S768I).2 Data are lacking on the efficacy of EGFR-TKIs against other uncommon EGFR mutations, particularly among various ethnic groups.1
Using the afatinib uncommon mutations database, researchers conducted a pooled analysis to investigate the efficacy of afatinib in the treatment of EGFR-mutant NSCLC in Asian and non-Asian patients who had not been treated with EGFR-TKIs.1 The database included randomized clinical trials, compassionate use and expanded access programs, phase 3b trials, noninterventional trials, and case reports/series. Uncommon EGFR mutations were classified into 5 categories (major uncommon [G719X, L861Q, and S768I], compound, exon 20 insertion [Ex20Ins], T790M, and other). Key end points included overall response rate (ORR), duration of response (DOR), and time to treatment failure (TTF).1
The study included a total of 693 patients treated with afatinib; of these patients, 45% were TKI-naïve (N = 315) and 55% were TKI-pretreated (N = 378); 43% were evaluable (N = 298), including 178 Asians and 120 non-Asians.1 The frequency of major uncommon EGFR mutations was 61.8% in Asian patients and 35.0% in non-Asian patients; 14.6% of Asian patients and 6.7% of non-Asian patients had compound mutations; 16.3% of Asian patients and 39.2% of non-Asian patients had Ex20Ins mutations; 10.7% of Asian patients and 11.7% of non-Asian patients had T790M mutations; and 9.6% of Asian patients and 10.8% of non-Asian patients had other uncommon EGFR mutations.1
In Asian patients, ORRs according to mutation were 66% for major uncommon, 81% for compound, 21% for Ex20Ins, 38% for T790M, and 79% for other; DORs were 14.7 months for major uncommon, 11.5 months for compound, 11 months for Ex20Ins, 8.1 months for T790M, and 9 months for other; the median TTF was 11.5 months for major uncommon, 11.5 months for compound, 4.5 months for Ex20Ins, 4.7 months for T790M, and 7.2 months for other.1 In non-Asian patients, ORRs according to mutation were 59% for major uncommon, 100% for compound, 23% for Ex20Ins, 17% for T790M, and 60% for other; DORs were 15.9 months for major uncommon, 18.6 months for compound, 10.7 months for Ex20Ins, 7.4 months for T790M, and 10.7 months for other; the median TTF was 9.0 months for major uncommon, 18.5 months for compound, 3.9 months for Ex20Ins, 2.9 months for T790M, and 10.7 months for other.1
The researchers concluded that afatinib demonstrates clinical activity against uncommon EGFR mutations in both Asian and non-Asian patients.1
1. Yang J C-H, et al. IASLC 2020. Paper ID40.
2. Park K, et al. Ther Adv Med Oncol. 2019;11:1758835919836374.