SWOG 0802: A randomized phase II trial of weekly topotecan with and without AVE0005 (aflibercept) in patients with platinum-treated extensive-stage small cell lung cancer (E-SCLC).

Abstract

7005 Background: Topotecan (T) (oral and IV) is the only FDA-approved second-line chemotherapy for patients with SCLC. Weekly T is associated with less toxicity than the daily x 5 regimen. AVE0005 (aflibercept) (A) is a novel recombinant human fusion protein which binds to circulating VEGF, thereby inhibiting its interaction with cell surface receptors. We sought to evaluate the efficacy and toxicity of weekly IV T (4 mg/m2) with or without A (6 mg/kg Q21D) in patients with relapsed SCLC following one line of platinum-based chemotherapy for E or limited-stage (L) SCLC. Methods: Patients were randomized 1:1 to T or A+T. Eligible patients had adequate organ function, ECOG PS 0-1, and no recent bleeding or cardiac events. Patients with brain metastases stable for ≥ 3 months prior to study entry were allowed. Primary endpoint was 3-month PFS. Patients were stratified as platinum-sensitive (PS) or platinum-refractory (PR). PR patients had progressed within 90 days of last chemotherapy for E and 6 months for L. This report is limited to the PR stratum. Results: 98 patients were registered. 1 was ineligible and 1 withdrew consent, leaving 96 evaluable for the primary endpoint (91 for toxicity (see Table for characteristics)). 3-month PFS was 26% for A+T versus 9% for T (P=0.01). Overall survival was similar in each arm (4.6 mos (A+T) versus 3.9 mos (T) (P=0.25)). There was 1 partial response with A+T. Disease control rate (DCR) was 28% with A+T and 12% with T. Toxicity was mainly hematologic with 14% and 19% of patients experiencing a Grade 4 event with T and A+T, respectively. There was one treatment-related death with T (renal failure). Conclusions: This study met its primary endpoint of improved 3-month PFS with A+T (p=0.01), warranting further study in the PR setting. Clinical benefit with A+T was achieved primarily through improved DCR. Toxicity was manageable and less than is seen with standard dose T. Accrual to the PS cohort is ongoing. [Table: see text]