Scholars@Duke publication: Chemoradiotherapy and gefitinib in stage III non-small cell lung cancer with epidermal growth factor receptor and KRAS mutation analysis: cancer and leukemia group B (CALEB) 30106, a CALGB-stratified phase II trial.

Chemoradiotherapy and gefitinib in stage III non-small cell lung cancer with epidermal growth factor receptor and KRAS mutation analysis: cancer and leukemia group B (CALEB) 30106, a CALGB-stratified phase II trial.

Publication , Journal Article

Ready, N; Jänne, PA; Bogart, J; Dipetrillo, T; Garst, J; Graziano, S; Gu, L; Wang, X; Green, MR; Vokes, EE; Cancer, Leukemia Group B, Chicago, IL,

Published in: J Thorac Oncol

September 2010

Published version (DOI) Link to item

INTRODUCTION: This study evaluated the addition of gefitinib to sequential or concurrent chemoradiotherapy (CRT) in unresectable stage III non-small cell lung cancer. METHODS: Between May 2002 and April 2005, 63 patients were entered before the study closing early. All received two cycles paclitaxel 200 mg/m and carboplatin area under the curve 6 intravenous plus gefitinib 250 mg daily. Poor risk stratum 1 (> or =5% weight loss and/or performance status 2) received radiotherapy 200 cGy for 33 fractions (6600 cGy) and gefitinib 250 mg daily. Good-risk stratum 2 (performance status: 0-1 weight loss and <5%) received the same RT with gefitinib 250 mg daily and weekly paclitaxel 50 mg/m plus carboplatin AUC 2. Consolidation gefitinib until progression was started after all toxicities were grade < or =2. RESULTS: Acute high-grade infield toxicities were not clearly increased compared with historical CRT data. Poor-risk (N = 21) median progression-free survival was 13.4 months (95% confidence interval [CI]: 6.4-25.2) and median overall survival 19.0 months (95% CI: 9.9-28.4). Good-risk (N = 39) median progression-free survival was 9.2 months (95% CI: 6.7-12.2), and median overall survival was 13 months (95% CI: 8.5-17.2). Thirteen of 45 tumors analyzed had activating epidermal growth factor receptor (EGFR) mutations, and 2 of 13 also had T790M mutations. Seven tumors of 45 had KRAS mutations. There was no apparent survival difference with EGFR-activating mutations versus wild type or KRAS mutation versus wild type. CONCLUSIONS: Survival of poor-risk patients with wild type or mutated EGFR receiving sequential CRT with gefitinib was promising. Survival for good-risk patients receiving concurrent CRT plus gefitinib was disappointing even for tumors with activating EGFR mutations.