Afatinib in Asian and Non-Asian Patients with EGFR Mutation–Positive NSCLC Harboring Uncommon Mutations

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

References
1. Yang J C-H, et al. IASLC 2020. Paper ID40.
2. Park K, et al. Ther Adv Med Oncol. 2019;11:1758835919836374.