A phase II trial of afatinib (BIBW 2992) in patients (pts) with advanced non-small cell lung cancer previously treated with erlotinib (E) or gefitinib (G).

Abstract

7524 Background: An unmet medical need exists in NSCLC pts after failure of E or G [reversible EGFR tyrosine kinase inhibitors (TKIs)], particularly in pts with T790M EGFR mutations, the most common mechanism of acquired resistance. Afatinib (A), an irreversible erbB family blocker, has preclinical activity against T790M. A was tested in this phase II study in pts enriched for acquired resistance to E or G. Methods: Pts in Japan with Stage IIIB/IV NSCLC (ECOG PS 0–1) who had progressed according to RECIST after 1–2 lines of chemotherapy and ≥12 wks of E or G received 50 mg A orally qd. The primary endpoint was objective tumor response. Results: Of 62 pts (F:48; M:14), 11.3%, 79% and 9.7% had received prior erlotinib, gefitinib or both, respectively. 65% of pts had achieved a prior response with E/G. Median duration between end of prior treatment with E/G and the start of A was 3 wks. 73% of pts were EGFR mutation-positive in their primary tumors. 82% of pts met the definition of acquired resistance to E/G by (1) EGFR mutation positive or (2) CR/PR to E/G or (3) SD for at least 6 months to E/G and (4) less than 4 wks off E/G. By investigator assessment, 13% of pts treated with A had a PR and the disease control rate (DCR >8 wks) was 72%; these values were 8.2% and 67%, respectively, by independent review. Median PFS was 4.6 months. Similar efficacy was seen in those pts meeting acquired resistance criteria (5.9% PR; 69% DCR; median PFS of 4.4 months, by independent review). Two pts had T790M mutations in their primary tumors; one, harbouring L858R+T790M, had a long SD (308 days). At data cut-off, the 25th percentile of OS was 10.6 months. Common adverse events included diarrhea, rash/acne, stomatitis, nail effects and decreased appetite. Conclusions: Pts in this study largely meet criteria for acquired resistance to first generation EGFR TKIs in NSCLC. Afatinib has demonstrated clinically meaningful efficacy (including 69% DCR >8 wks and 4.4 month median PFS) in these pts.