P3-097: Regressions 14 days following bevacizumab as a single agent as part of neoadjuvant chemotherapy for resectable non–squamous NSCLC

Abstract

The addition of bevacizumab to standard chemotherapy improves response rate and overall survival in advanced non-squamous NSCLC, but limited data exist on response to treatment with bevacizumab alone. As part of a trial evaluating bevacizumab with docetaxel and cisplatin (DC) as induction therapy for resectable stage IB-IIIA NSCLC, we determined the effect of single agent bevacizumab on tumor size 14 days following a single dose. Eligibility was limited to patients with stage IB-IIIA resectable NSCLC. Patients with a contraindication to bevacizumab (squamous histol-ogy, central tumor, hemoptysis) received only docetaxel (75 mg/m2) and cisplatin (75 mg/m2) q3 weeks for 4 cycles. If patients had no contrain-dications to bevacizumab, they underwent a baseline CT, a single dose of bevacizumab (15 mg/kg) on day 1, a second CT on day 14, and then 3 cycles of bevacizumab with docetaxel and cisplatin followed by one cycle without bevacizumab. WHO criteria were used to assess response. Following resection, patients in both arms received adjuvant bevacizumab for 1 year. 22 patients have been enrolled to date. Among the 13 patients who received induction bevacizumab, 10 had IIIA disease, 1 had IIB, and 2 had IB. The average reduction in tumor size (see figure) 14 days after bevacizumab alone was 13% (range +1.6% -24%). Among the 10 who had surgery thus far, 6 had PR. Resections were R0 in 6 patients, R2 in 1, and not resectable for 2; 5 patients were downstaged. During 45 cycles, there has been 1 episode of Grade 2 pre-operative hemoptysis, 1 Grade 3 post-operative GI bleed, and 1 febrile neutropenia. Among patients receiving no induction bevacizumab, 4 had IIIA disease, 1 had IIB, and 3 had IB. All 8 of these patients had had surgery and 6 had PR. Resections were R0 in all cases; 5 were downstaged. The chemotherapy drug delivery was 95% for both preoperative treat-ment arms. Treatment with a single dose of bevacizumab causes measurable decrease in tumor size in non-squamous NSCLC. The study is ongoing; we intend to determine the association between 14 day bevacizumab response and downstaging with neoadjuvant bevacizu-mab/docetaxel/cisplatin, the primary endpoint of the study, to determine whether this measurement might serve as an early marker of biologic effect. Patient accrual continues. Supported by Genentech, Inc.