Phase II study of afatinib, an irreversible ErbB family blocker, in demographically and genotypically defined lung adenocarcinoma

Objectives: Afatinib, an oral irreversible ErbB family blacker, has demonstrated efficacy in patients with epidermal growth factor receptor (EGFR) mutation-positive advanced lung adenocarcinoma. Other potential biomarkers predicting response to afatinib, such as human epidermal growth factor receptor-2 (HER2) mutations and EGFR gene amplification, have not been validated yet. This phase II study investigated whether afatinib conferred clinical benefit in cohorts of adenocarcinoma patients with: (1) EGFR mutation and failing on erlotinib/gefitinib; or (2) increased copy number of EGFR by fluorescence in situ hybridization (FISH); or (3) HER2 mutation. Materials and methods: Patients started daily afatinib 50 mg monotherapy. Upon disease progression, patients could continue, at the investigator's discretion, afatinib (40 mg) with the addition of paclitaxel (80 mg/m(2) weekly for 3 weeks/4-week cycle). Endpoints included confirmed objective response (OR), progression-free survival (PFS), disease control, and safety. Results: Of 41 patients treated (cohort 1: n =32; cohort 2: n=2; cohort 3: n=7), 33 received afatinib monotherapy; eight subsequently received afatinib plus paclitaxel. With afatinib monotherapy, one patient achieved a confirmed OR (partial response [PR]; cohort 2). Two further patients achieved unconfirmed PRs (one each in cohort 1 and cohort 3). Disease control was achieved by 17/32 (53%), 2/2(100%) and 5/7 (71%) patients in cohorts 1, 2 and 3, respectively. In patients receiving combination therapy (median PFS: 6.7 weeks), one (cohort 3) had confirmed PR of 41.9 weeks. The most common afatinibrelated adverse events were diarrhea (95%) and rash/acne (80%). Conclusion: Afatinib demonstrated signs of clinical activity in heavily pretreated patients with activating HER2 or EGFR mutations or EGFR FISH-positive tumors. (c) 2015 Elsevier Ireland Ltd. All rights reserved.