Phase II study of concurrent cetuximab (C225) plus definitive thoracic radiotherapy (XRT) followed by adjuvant docetaxel in poor prognosis patients with locally advanced non-small cell lung cancer (LA-NSCLC).

Abstract

7065 Background: Recursive partitioning analysis has shown that ECOG PS ≥ 2, male gender, or age > 70 are prognostic of poor outcome in LA-NSCLC pts. Concurrent chemoradiotherapy improves survival, but toxicity is concerning in this frail pt cohort. We therefore opened this trial of concurrent definitive-dose XRT (70 Gy in 35 fractions) and C225 (250 mg/m2/dose), followed by adjuvant C225 and docetaxel (60 mg/m2 q3weeks x 3 cycles). Methods: Eligible patients had pathologically-proven LA-NSCLC (stage IIA – “dry” IIIB), not surgically resectable. They had ECOG PS 2 OR weight loss ≥5% in 3 months OR age >70. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From 5/2008 to 11/2010, 32 pts were evaluated for our single-institution, IRB-approved prospective clinical trial. 3 pts were screen-failures and 2 more withdrew consent prior to treatment, leaving 27 evaluable patients. 1 was removed due to poor therapy compliance and 2 were taken off trial due to grade 3 toxicity from the C225 loading dose, but were followed under intent-to-treat analysis. Median follow-up and OS was 10.5 months. Median PFS was 7.8 months. ORR = 59.3%. 8 early/sudden deaths were reported, so the trial closed early: radiation pneumonitis (RP) was the apparent cause in 1 and probably/possibly in 4 others, with insufficient information in 2 additional pts; 1 pt died of failure to thrive. Of the remaining pts, 3 developed grade 3+ RP and 2 had grade 2 RP. Conclusions: Pts enrolled on this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.3 months) and comparable OS compared with good-PS historical controls (10.5 vs 11.9 months) treated with RT (Werner-Wasik M et al. Int J Radiat Oncol Biol Phys. 2000;48:1475-82). However, pulmonary toxicity is a concern. Analysis of RP events is ongoing. Updated results will be presented at the meeting.