A phase II study of cisplatin (P) plus etoposide (E) plus bevacizumab (B) for previously untreated extensive stage small cell lung cancer (SCLC) (E3501): A trial of the Eastern Cooperative Oncology Group

Abstract

7564 Background: Scientific evidence supports the concept that the growth of solid tumors, including SCLC, is dependent on angiogenesis. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has been shown to improve survival when combined with chemotherapy in non-small cell lung cancer. PE is a standard regimen for use in SCLC. Thus, we proposed this study of PE plus B in patients (pts) with previously untreated extensive stage SCLC. Methods: Pts with previously untreated extensive SCLC with a performance status 0–2, received P (60 mg/m2) IV followed by E (120 mg/ m2) IV followed by B (15 mg/kg) IV infusion on day 1, with E repeated on days 2 and 3 of a 21-day cycle for 4 cycles or until progressive disease (PD). Pts not experiencing PD continued bevacizumab until disease progression or unacceptable toxicity. The primary endpoint was per cent of patients alive at 6 months. Results: From 6/8/04 to 8/18/06 (includes a ten month accrual suspension to evaluate data), 64 eligible pts were accrued. Patient characteristics: median age of 65.5 years (range: 45–83), 44% males, 95% Caucasian and 9% were performance status = 2. A median of 6 cycles of treatment were administered (range: 1–12). There is toxicity data on 58 pts. The most common treatment-related grade 3 & 4 toxicities were: neutropenia (7 & 26 pts), thrombocytopenia (8 & 2 pts), fatigue (10 pts, grade 3 only), hypertension (4 pts, grade 3 only), febrile neutropenia (2 pts) and dehydration (3 pts, grade 3 only). Two pts experienced grade 5 toxicities (hypotension and infection with grade ¾ neutropenia). There were no grade ≥3 hemorrhagic events. Response information is available on 39 pts. There have been 4 complete responses and 23 partial responses for an overall response rate of 69% (90% exact CI: (55%, 81%). The proportion of pts alive and progression- free at 6 months was 33% (95% CI: 17%, 49%). Conclusions: Preliminary results indicate that the addition of B to the combination of PE in patients with previously untreated extensive stage SCLC appears promising. A randomized phase III trial comparing PE to PE + B is under consideration. No significant financial relationships to disclose.