Experience from Asian centers in a named-patient-use program for afatinib in patients with advanced non-small-cell lung cancer who had progressed following prior therapies, including patients with uncommon EGFR mutations

Abstract

Background This study evaluated outcomes among patients with advanced/metastatic non-small-cell lung cancer (NSCLC) treated at Asian centers participating in the global named-patient-use (NPU) program for afatinib. Methods Patients had progressed after initial benefit with erlotinib or gefitinib, and/or had an EGFR or HER2 mutation, had no other treatment options, and were ineligible for afatinib trials. The recommended starting dose of afatinib was 50 mg/day. Dose modifications were allowed, and afatinib was continued as long as deemed beneficial. Response and survival information was provided voluntarily. Safety reporting was mandatory. Results 2242 patients (26% aged ≥ 70 years, 96% with adenocarcinoma) received afatinib at centers in 10 Asian countries. Most were heavily pre-treated, including prior treatment with erlotinib or gefitinib. Of 1281 patients tested, 1240 had EGFR mutations (common: 1034/1101; uncommon: 117/1101). There were no new safety signals, the most common adverse events being rash and diarrhea. Objective response rate (ORR) was 24% overall (n = 431 with data available), 27% for patients with common EGFR mutations (n = 230) and 28% for those with uncommon mutations (n = 32); median time to treatment failure (TTF) in these groups was 7.6 months (n = 1550), 6.4 months (n = 692) and 8.4 months (n = 83), respectively. In patients with EGFR exon 20 insertions (n = 23) and HER2 mutations (n = 12), median TTF exceeded 12 months. Conclusions Patient outcomes in this study were similar to those reported in the analysis of the global NPU. Afatinib achieved clinical benefits in patients with refractory NSCLC. ORR and TTF were similar between patients with tumors harboring uncommon and common EGFR mutations.

Impact of Dose Reduction of Afatinib Used in Patients With Non–Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

“…Afatinib was approved by the U.S. Food and Drug Administration in 2013. As the second-generation EGFR-TKI, afatinib not only showed a better survival benefit for patients with common EGFR mutations (exon 19del and exon 21 L858R) but was also effective for patients with rare mutations ( Banno et al, 2018 ; Chang et al, 2021 ). However, the incidence of adverse reactions was also significantly higher than that of the first- and third-generation drugs.…”

Uncommon and Rare EGFR Mutations in Non-Small Cell Lung Cancer Patients with a Focus on Exon 20 Insertions and the Phase 3 PAPILLON Trial: The State of the Art

“…Despite being less representative, these mutations are associated with a lower sensitivity to EGFR-TKIs, with most data being available on the clinical activity of afatinib against ucEGFRmuts [5,10,11].…”

Overview on Therapeutic Options in Uncommon EGFR Mutant Non-Small Cell Lung Cancer (NSCLC): New Lights for an Unmet Medical Need

“…Less is known about other mutations, which are defined as uncommon mutations, accounting for approximately 10-15% of all EGFR mutations (ranging between 1.0% and 18.2% across different series). These mutations usually show lower sensitivity to EGFR-TKIs, with some exceptions observed with the use of afatinib [9][10][11][12][13].…”