Phase II study of afatinib, an irreversible ErbB family blocker, in demographically and genotypically defined non-small cell lung cancer (NSCLC) patients.

Abstract

8063 Background: EGFR mutation+ (M+) NSCLC pts have an improved response to EGFR TKIs vs non-M+ pts. Data on EGFR FISH+ (gene amplified) and HER2 M+ pts are, however, limited. Afatinib is an irreversible ErbB Family Blocker with efficacy in Ph II/III trials in EGFR M+ NSCLC. This exploratory, open-label trial assessed afatinib in 3 genotypically and demographically defined NSCLC groups. Methods: Never/ex-smokers with stage IIIB/IV lung adenocarcinoma with EGFR M+ tumors who had failed prior EGFR TKIs, HER2 M+ tumors independent of prior therapy, or EGFR FISH+ tumors who received ≤3 prior chemotherapies were enrolled. Afatinib 50 mg qd was administered until disease progression or intolerable adverse events. Tumor assessments (RECIST 1.0) were performed every 8 wks. Pts who progressed on afatinib but experienced clinical benefit could continue treatment with afatinib 40 mg qd + paclitaxel 80 mg/m² qw on days 1, 8 and 15 every 28-day cycle. Primary endpoint: Confirmed objective response. Results: 41 pts were treated: 63% female; median age 63 yrs; 68% never smokers; 32% ex-smokers. 33 pts received afatinib monotherapy only; 8 pts received afatinib followed by afatinib/paclitaxel combination therapy. 78% (n=32) of pts were EGFR M+, 5% (n=2) were EGFR FISH+ and 17% (n=7) were HER2 M+. For afatinib monotherapy, 1 confirmed partial response (PR) was observed (EGFR FISH+), stable disease (SD) was seen in 5/7 HER2 M+, 2/2 EGFR FISH+ and 17/32 EGFR M+ pts, and overall disease control (DC) rate was 59% (n=24); mean duration of DC was 26 wks.Median PFS was 16 wks (17 wks in HER2 M+ pts). Of 8 afatinib/paclitaxel-treated pts, 1 had a confirmed PR and 2 had SD; median PFS was 7 wks. Most frequently reported drug-related AEs in afatinib monotherapy pts were diarrhea (n=39; grade ≥3 n=13), rash/acne (n=33; grade ≥3 n=4) and stomatitis (n=19; grade ≥3 n=2). In the combination arm these were diarrhea (n=4; grade ≥3 n=1) and nausea (n=3; grade ≥3 n=0). Conclusions: Efficacy of afatinib in EGFR M+ NSCLC pts has been established in previous trials. Novel activity of afatinib in HER2 M+ and EGFR FISH+ NSCLC pts has been demonstrated here, with a manageable safety profile of afatinib in the overall population. Clinical trial information: NCT00730925.