In an Italian phase III trial reported in the Journal of Clinical Oncology, Marcello Tiseo, MD, of Azienda Ospedaliero-Universitaria, Parma, Italy, and colleagues found that adding first-line bevacizumab (Avastin) to cisplatin/etoposide did not prolong overall survival in patients with extensive-disease small cell lung cancer.
In the open-label trial, 204 treatment-naive patients from 29 sites in Italy were randomized between November 2009 and October 2015 to receive cisplatin/etoposide with (n = 101) or without bevacizumab (n = 104). Treatment consisted of cisplatin at 25 mg/m2 on days 1 to 3 and etoposide at 100 mg/m2 on days 1 to 3 every 3 weeks for a maximum of 6 cycles with or without bevacizumab at 7.5 mg/kg on day 1 every 3 weeks; patients without disease progression in the bevacizumab group continued to receive bevacizumab for a maximum of 18 cycles or until disease progression.
The primary endpoint was overall survival in the intent-to-treat population. Five patients in the bevacizumab group and one patient in the control group dropped out of the study before receiving study medication.
Overall Survival and Toxicity
Median follow-up was 34.9 months. Median overall survival was 9.9 months in the bevacizumab group vs 8.9 months in the control group (hazard ratio [HR] = 0.78, P = .113), with 1-year survival of 37% vs 25%. A survival benefit was observed among 41 patients in the bevacizumab group who received maintenance bevacizumab (HR = 0.60, P = .011).
Median progression-free survival was 6.7 vs 5.7 months (HR = 0.72, P = .030). Response was observed in 58.4% vs 55.3% of patients (odds ratio = 1.13, P = .657).
Grade 3 or 4 hematologic toxicity in the bevacizumab and control groups included neutropenia (46% in both), leukopenia (15% vs 14%), thrombocytopenia (4% vs 11%), and anemia (3% vs 10%). Among nonhematologic grade 3 or 4 toxicities, hypertension (6% vs 1.0%) and thrombosis (5% vs 3%) were more common in the bevacizumab group and fatigue (8% vs 15%) and nausea (1% vs 5%) were more common in the control group.
The investigators concluded: “The addition of bevacizumab to cisplatin and etoposide in the first-line treatment of [extensive-disease small cell lung cancer] had an acceptable toxicity profile and led to a statistically significant improvement in progression-free survival, which, however, did not translate into a statistically significant increase in [overall survival]. Further research with novel antiangiogenic agents, particularly in the maintenance setting, is warranted.”
The study was supported by the Agenzia Italiana del Farmaco. ■