Phase II Study of Cisplatin Plus Etoposide and Bevacizumab for Previously Untreated, Extensive-Stage Small-Cell Lung Cancer: Eastern Cooperative Oncology Group Study E3501

To investigate the efficacy and safety of bevacizumab plus cisplatin and etoposide in patients with extensive-stage disease, small-cell lung cancer (ED-SCLC). In this phase II trial, 63 patients were treated with bevacizumab 15 mg/kg plus cisplatin 60 mg/m(2) and etoposide 120 mg/m(2), which was followed by bevacizumab alone until death or disease progression occurred. The primary end point was the proportion of patients alive at 6 months without disease progression (ie, progression-free survival [PFS]). Secondary end points included overall survival (OS), objective response rate, and toxicity. Correlative studies were performed to explore the relationship between baseline and changes in plasma vascular endothelial growth factor (VEGF), soluble cell adhesion molecules (ie, vascular cell adhesion molecule [VCAM], intercellular cell adhesion molecule [ICAM], and E-selectin) and basic fibroblast growth factor and outcome. The 6-month PFS was 30.2%, the median PFS was 4.7 months, and OS was 10.9 months. The response rate was 63.5%. The most common adverse event was neutropenia (57.8%). Only one patient had grade 3 pulmonary hemorrhage. Patients who had high baseline VCAM had a higher risk of progression or death compared with those who had low baseline VCAM levels. No relationships between outcome and any other biomarkers were seen. The addition of bevacizumab to cisplatin and etoposide in patients with ED-SCLC results in improved PFS and OS relative to historical controls who received this chemotherapy regimen without bevacizumab. This regimen appears to be well tolerated and has minimal increase in toxicities compared with chemotherapy alone. Baseline VCAM levels predicted survival, but no other relationships among treatment, biomarkers, and outcome were identified.