Phase II study of afatinib as third-line treatment for patients in Korea with stage IIIB/IV non-small cell lung cancer harboring wild-type EGFR

Background. This phase II single-arm trial evaluated afatinib, an irreversible inhibitor of the ErbB receptor family as thirdline treatment of Korean patients with advanced non-small cell lung cancer (NSCLC) and tumors with wild-type EGFR. Currently, no standard therapy exists for these patients. Methods. Eligible patients had stage IIIB/IV wild-type EGFR lung adenocarcinoma and had failed to benefit from two previous lines of chemotherapy but had not received anti- EGFR treatment. Patients received oral afatinib at 40 mg per day until disease progression or occurrence of intolerable adverse events (AEs). The primary endpoint was confirmed objective tumor response (OR) rate (confirmed complete response [CR] or partial response [PR]). Secondary endpoints included disease control rate (DCR; OR or stable disease for ≥ 6 weeks), progression-free survival (PFS), and safety. Results. Forty-two patients received afatinib treatment, and 38 of those were included in efficacy analyses. No confirmed CRs or PRs were reported. DCR was 24% (9 of 38 patients), with a median disease control duration of 19.3 weeks. Median PFS was 4.1 weeks (95% confidence interval: 3.9-8.0). Frequently reported AEs (mainly grades 1 and 2) were rash/acne (88%), diarrhea (62%), and stomatitis (57%). Conclusion. Heavily pretreated patients with wild-type EGFR NSCLC treated with afatinib monotherapy did not experience an objective response and only 24% had disease stabilization lasting more than 6 weeks. AEs were manageable and consistent with the expected safety profile.