Adjuvant carboplatin, docetaxel, bevacizumab, and erlotinib versus chemotherapy alone in patients with resected non-small cell lung cancer: A randomized phase II study of the Sarah Cannon Research Institute (SCRI).

Abstract

7035 Background: Adjuvant chemotherapy improves overall survival (OS) in patients (pts) with resected non small cell lung cancer (NSCLC). Bevacizumab and erlotinib improve survival in pts with advanced unresectable NSCLC. This randomized phase II multicenter pilot study examined the safety and efficacy of chemotherapy and bevacizumab followed by bevacizumab and erlotinib vs. chemotherapy alone in pts with resected NSCLC. Methods: Eligible pts had completely resected (R0) stage IB, II, or IIIA NSCLC (TNM 6th Ed.), any NSCLC histology, and an ECOG PS 0-1. Pts were excluded for preoperatively confirmed N2 disease; N2 disease found at surgery was allowed. Pts were randomized 1:1 to carboplatin AUC=5, docetaxel 60 mg/m2, and bevacizumab 15 mg/kg IV d1 q 21 days x 4, followed by maintenance bevacizumab 15 mg/kg d1 and erlotinib 150 mg PO daily x 8 cycles (Arm A) or carboplatin AUC=6 and docetaxel 75 mg/m2 IV d1 q 21 days x 4 (Arm B). The primary endpoint was 1-year disease-free survival (DFS); safety, 2-year DFS, and OS were secondary endpoints. Results: 106 pts were enrolled from 2/2008 to trial closure 1/2012 (A=54; B=52). Baseline features were balanced: age 63 yrs (42–87); 54% male; IB (46%), IIA (8%), IIB (27%), IIIA (18%); adenocarcinoma (61%), squamous (31%). Arm A received a median of 7 cycles (1-12); Arm B 4 cycles (1-4). 1- and 2-year DFS by stage are shown in the table. The 1-year DFS for all stages were 78% (A) and 88% (B) (p=.66). The 3-year OS for all stages were 81% (A) and 63% (B). Neutropenia was the most common grade 3/4 hematologic toxicity (A 18%; B 29%). Severe non-hematologic toxicity was rare: fatigue (A 6%), diarrhea (B 6%). Bronchopleural fistulae occurred in 2 pts (1 per arm), and grade 3 gastrointestinal hemorrhage was seen in 1 pt (A). Conclusions: This pilot study demonstrated that bevacizumab and erlotinib could be safely added to platinum-doublet chemotherapy in the adjuvant setting in all histologies. Larger randomized studies will best define the roles of these agents in pts with resectable NSCLC. [Table: see text]