Combination of Aflibercept and Topotecan Shows Activity in Patients With Small Cell Lung Cancer

A phase II trial presented at ASCO 2012 showed that aflibercept (Zaltrap) combined with topotecan (Hycamtin) achieved slightly higher rates of progression-free survival (PFS) and disease control in patients with platinum-refractory, extensive-stage small cell lung cancer (SCLC) compared with topotecan alone.

Topotecan, is approved by the FDA to treat patients with SCLC whose disease has not improved after first-line chemotherapy. It is typically prescribed to be taken once daily for 5 days every 21 days, although weekly administration has been tested in clinical trials and is associated with less toxicity. Aflibercept is a novel recombinant human fusion protein that binds to VEGF, which promotes angiogenesis and tumor progression, and inhibits interaction with cell surface receptors.

In the phase II SWOG 0802 study, patients were randomized to receive topotecan with aflibercept or topotecan alone. In order to be eligible, patients had to have an ECOG performance status score of 0-1 with no recent bleeding or cardiac events. Because patients with SCLC commonly experience brain metastases, patients with brain metastases were allowed to enroll in the study if the disease had been stable for at least 3 months prior to study entry. The study used a 3-month period of PFS as the primary endpoint. Results presented at ASCO represented the platinum-refractory cohort of the study and not the platinum-sensitive cohort.

The study enrolled 98 evaluable platinum-refractory patients. A 3-month PFS period was achieved by 27% of patients who received the combination of aflibercept and topotecan compared with 10% in the topotecan-alone arm (P = .01). Overall survival (OS) was similar in both arms of the study, with patients who received the combination therapy achieving a median OS of 4.6 months compared with 4.2 months in the topotecan-alone arm (P = .35). The rate of disease control (stable disease or better) was 28% in the combination arm and 15% in the topotecan-alone arm.

Grade 4 hematologic toxicities were observed in 15% of patients receiving the combination treatment and 10% of patients receiving topotecan alone. Neutropenia and thrombocytopenia were the most common grade 4 hematologic toxicities across both arms.

“While the objective response rate was low, disease control was improved with the combination,” said Jeffrey W. Allen, MD, associate director of clinical research at the University of Tennessee Cancer Institute in Memphis, who was the lead author of this study. Allen added that more research of this drug combination is warranted, particularly in the platinum-refractory setting.

Allen JW, Moon J, Gadgeel SM, et al. SWOG 0802: A randomized phase II trial of weekly topotecan with and without AVE0005 (aflibercept) in patients with platinumt-reated extensive-stage small cell lung cancer (E-SCLC). J Clin Oncol. 2012;30(suppl; abstr 7005).