Irinotecan, carboplatin, and bevacizumab in untreated extensive-stage small-cell lung cancer: D1-05

Bevacizumab’s role in the treatment of small-cell lung cancer is unknown. A multicenter phase II trial with bevacizumab and chemotherapy was conducted in patients with untreated extensive-stage small-cell lung cancer. The primary objective of this trial was to improve the historical median time to progression (TTP) of 6 months by 40%. Eligibility criteria included: no prior chemotherapy for small-cell lung cancer, no active brain metastases, normal organ function, no hemoptysis, ECOG PS 0-1, measurable disease, and signed informed consent. Treatment consisted of: irinotecan 60mg/m2 IV days 1, 8, 15, carboplatin AUC=4 IV day 1, and bevacizumab 10 mg/kg IV days 1 and 15 every 28 days. Restaging studies were performed every 2 cycles (8 weeks). If there was no evidence of progressive disease after 4-6 cycles of combination therapy, patients went on to receive maintenance bevacizumab for 6 months. 44 pts have been enrolled from 2/06 to 3/07 (n=50 planned), with a median follow-up of 9 months. Baseline features included: median age 66 years (range 46-81); male/female, 57%/43%; 3 patients (7%) with previously treated brain metastases; 89% current or former smokers; and ECOG PS 0/1, 32%/68%. The objective response rate was 72% (95% CI 55%-85%), including 2 complete responses and 21 partial responses. 7 patients (22%) had stable disease and 2 patients had progressive disease at restaging. 12 patients were not evaluable due to: comorbidity (off study), 2 patients; being too early for restaging, 10 patients. TTP and overall survival data are not mature at the time of this analysis. Grade 3/4 toxicity has been limited: diarrhea (26%), fatigue (13%), and neutropenia (13%). There has been no significant bleeding to date. Bevacizumab can be safely added to carboplatin and irinotecan in the first-line treatment of extensive-stage small-cell lung cancer. Analysis of TTP will soon be mature to better estimate bevacizumab’s role in this setting. Ultimately, randomized trials will best assess bevacizumab’s efficacy in small-cell lung cancer treatment.