Single agent bevacizumab and bevacizumab in combination with docetaxel and cisplatin as induction therapy for resectable IB-IIIA non-small cell lung cancer

Abstract

18045 Background: Bevacizumab (Bev) improves response and survival in patients with advanced non-squamous lung cancer with chemotherapy however there are limited data as single agent therapy and in early stage NSCLC. Methods: Patients with resectable stage IB-IIIA NSCLC were eligible. Patients with adenocarcinoma (Cohort 1) received preoperative Bev and docetaxel and cisplatin (DC). Patients with squamous histology, central location or recent hemoptysis received DC induction therapy without Bev (Cohort 2). Cohort 1 received Bev (15 mg/kg) followed by CT 2 weeks later to assess single agent Bev response. Subsequently D (75 mg/m2) and C (75 mg/m2) were given q 3 weeks; an additional 2 cycles of Bev was administered with C2 and C3 of DC (total of 3 preoperative doses of Bev). Cohort 2 received DC alone followed by resection. Both cohorts received adjuvant Bev x 1 year. Study endpoints included response to single agent Bev, downstaging, safety and survival. Results: 19 patients of planned 70 were enrolled (11 Cohort 1 and 8 Cohort 2). On Cohort 1, there were 2 clinical stage IIB and 9 IIIA patients. After single agent Bev (by bimensional measurement), > 10% reduction in tumor size was observed after 2 weeks in 6/11 patients (- 20%, 15%, 16%, 15%, 13% and 20%). After Bev + DC, there were 6/10 (60%) PRs and DC delivery was 96%. 6/10 patient underwent R0 resection; 1 R2 and 2 were unresectable. 1 patient developed hemoptysis preoperatively and 1 patient developed an upper GI bleed post-operatively. There were otherwise no Bev related operative complications observed. 5/9 patients were downstaged by induction treatment. 3 patients received adjuvant bevacizumab to date (median 5.7 cycles). 8 patients were treated on Cohort 2 (3 with stage IB, 1 with IIB and 4 with IIIA). All 8 patients underwent R0 resection. DC delivery was 94% and there were 6/8 PRs. Downstaging was observed in 5/8 patients and 6/8 are receiving adjuvant Bev (median # cycles to date = 6.7). Conclusions: Bev as a single agent demonstrates regression of tumors after 2 weeks. To date, Bev has been safely administered in the neoadjuvant and adjuvant setting. Preoperative chemotherapy is well tolerated with more than 90% full dose drug delivery. The study is ongoing. Supported by Genentech, Inc. [Table: see text]