Phase IIb/III double-blind randomized trial of BIBW 2992, an irreversible, dual inhibitor of EGFR and HER2 plus best supportive care (BSC) versus placebo plus BSC in patients with NSCLC failing 1–2 lines of chemotherapy (CT) and erlotinib or gefitinib (LUX- Lung1): A preliminary report

8062 Background: No approved therapy exists for NSCLC patients (pts) who have failed chemotherapy (CT) and the reversible epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), erlotinib (E) or gefitinib (G). The efficacy of BIBW 2992 (Tovok), a potent, irreversible inhibitor of EGFR and human epidermal growth factor receptor 2 (HER2) with preclinical activity against the secondary resistance mutation T790M, in pts progressing after initial clinical benefit on E/G is being assessed in this randomized trial. Methods: Pts with advanced adenocarcinoma of the lung (Stage IIIB/IV; ECOG 0–2), who have failed one or two lines of CT (including platinum) and progressed following at least 12 weeks of E or G are randomized in a 2:1 ratio to receive BSC plus either oral BIBW 2992 50 mg qd or placebo until disease progression or unacceptable toxicity. Primary endpoint is overall survival, with progression-free survival, objective response and clinical benefit rate and duration, safety and quality of life being secondary endpoints. Enrollment of 400 pts is planned (HR=0.70, 85% power). An unblinded interim analysis of tumor response and safety by the independent Data Monitoring Committee (DMC) after the first 40 evaluable pts treated with BIBW 2992 will determine continuation to full accrual. Results: From May to November 2008, 145 pts have been randomized and 76 are still on treatment. Demographics (n=145): median age 59 (range: 30–82); female 68%, current/ex-smokers 38%; metastatic disease 91%, ECOG 0–1 92%; Asian origin 68%. 50% had one prior line of CT. Main prior EGFR-TKI was G in Asians (70%) and E in non-Asians (85%). 40% of pts had achieved a PR or CR on previous treatment with E/G. Duration of prior E/G treatment was >24 weeks and >48 weeks in 80% and 40% of pts, respectively. As expected, diarrhea, rash, anorexia, stomatitis, paronychia, nausea and vomiting were the most frequently observed adverse events. Conclusions: The trial is continuing recruitment after DMC review of efficacy and safety and updated demographics and blinded safety data will be reported. [Table: see text]