Multicenter phase II study of cetuximab (C) with concomitant radiotherapy (RT) followed by consolidation chemotherapy (CT) in locally advanced non-small cell lung cancer (NSCLC).

Abstract

7019 Background: C, an anti-EGFR monoclonal antibody, enhances the efficacy of both RT and CT. We evaluated a novel strategy of RT plus C followed by consolidation CT plus C for the treatment of stage III NSCLC. Methods: Eligible were pts with unresectable stage IIIA or IIIB NSCLC, ECOG performance status (PS) 0-1, no history of pulmonary fibrosis and adequate end organ function. Pts were treated with chest RT (73.5 Gy in 35 fractions/7 weeks, once daily, with lung and tissue heterogeneity corrections (63 Gy without corrections) and C 250 mg/m2 weekly during RT (after a loading dose of 400 mg/m2 the week prior to starting RT). C was continued after RT completion and during consolidation therapy for 26 weeks. Paclitaxel 200 mg/m2 and carboplatin AUC of 6 were given for 3 cycles (every 3 weeks) after 4-6 weeks from RT. Primary endpoint was the overall survival. Results: Thirty-eight eligible pts were analyzed (2 ineligible pts were excluded from analysis). 25 males; median age 67 yrs; PS 0: 19, PS 1: 19; 14 adenocarcinomas, 10 squamous, 14 non-otherwise specified; Stage: 13 IIIA, 25 IIIB. Median corrected RT dose: 73.5 Gy (56-73.5); median C doses: 18. 33 pts received at least 1 cycle of consolidation. Grade 3/4 toxicities during RT/C were (in > 1 pt): pulmonary embolism (2/2), infection (2/1), fatigue (2/0) and rash (3/0). Grade 3/4 toxicities during consolidation: neutropenia (7/9), neutropenic fever (0/2), lymphopenia (4/0), infection (0/1), rash (2/0). One pt died of pneumonitis, possibly related to C. Best response using RECIST in 31 evaluable pts: 4 CR, 17 PR, 4 SD, 6 PD. With a median follow up of 17.75 months, the median OS and PFS were 17.1 and 9.3 months, respectively. Pts with EGFR positive tumors by FISH (17 of 28 tested) had a trend towards better PFS (p=0.07). Conclusions: C with RT followed by consolidation therapy was associated with acceptable toxicities and efficacy comparable to RT/CT. There was no associated grade 3-4 esophagitis. Supported in part by P50 CA090440.