Chemoradiotherapy (CRT) and gefitinib (G) in stage III non-small cell lung cancer (NSCLC): A CALGB stratified phase II trial

Abstract

7046 Background: G is a small molecule inhibitor of EGFR with activity in advanced NSCLC and preclinical evidence of being a radiosenitizer. Methods: Patients with stage III NSCLC were assigned to stratum 1 (PS 0–1>5% weight loss and/or PS 2) or stratum 2 (PS 0–1weight loss < 5%). Both strata received induction paclitaxel (P) 200 mg/m2 and carboplatin (C) AUC of 6 IV every three weeks for 2 cycles plus G 250 mg PO/day. G was removed 4/05 from induction therapy as stage IV studies showed no benefit from adding G to P and C. Stratum 1 then received RT 200 cGy for 33 fractions (total dose 6,600 cGy) and G 250 mg PO /day. Stratum 2 received the same RT with concurrent G 250 mg/day, and P 50 mg/m2 plus C AUC of 2 weekly for 7 doses. Maintenance G was started after all toxicities were grade ≤2. Results: Activation was 5/02 and administrative closure 5/04 due to results from SWOG S0023. 64 patients were accrued and 59 (20 stratum 1, 39 stratum 2) were eligible and analyzed: median age 67, male 74%, adeno 30%, squamous 45%, other 25%, IIIA 51%, IIIB 49%. There was no clear increase for acute high-grade infield toxicities compared to CRT alone (reported PASCO 2004). Best response for stratum 1 was PR 29% for induction (RR 29%, 95% CI 10%-56%) and CR 5%, PR 45% full treatment (RR 50%, 95% CI 27%-73%); for stratum 2 PR 13% for induction (RR 13%, 95% CI 3%-34%) and CR 5%, PR 76% full treatment (RR 81%, 95% CI 65%-92%). Stratum 1 “poor risk” median failure free survival (FFS) was 11.5 months (95% CI 5.6–21.2), one year survival 60% (95% CI 33%-79%) and median overall survival (OS) 19.0 months (95% CI 7.2–21.2). Stratum 2 “good risk” median FFS was 9.2 months (95% CI 6.7–12.0), one year survival 47% (95% CI 30%–63%) and median OS was 12.0 months (95% CI 8.5–18.6). EGFR and Ras mutation analysis on tumor biopsies (n = 50) will be presented. Conclusions: Small sample size prevented planned data analysis. Survival of “good risk” patients on stratum 2 (CRT + G) was disappointing. The promising survival of the small number of “poor risk” patients on stratum 1 (RT + G) justifies a follow-up phase II trial of induction chemotherapy followed by RT with a concurrent small molecule EGFR inhibitor. [Table: see text]