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

IntroductionThis study evaluated the addition of gefitinib to sequential or concurrent chemoradiotherapy (CRT) in unresectable stage III non-small cell lung cancer.MethodsBetween May 2002 and April 2005, 63 patients were entered before the study closing early. All received two cycles paclitaxel 200 mg/m2 and carboplatin area under the curve 6 intravenous plus gefitinib 250 mg daily. Poor risk stratum 1 (≥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: 0–1weight loss and <5%) received the same RT with gefitinib 250 mg daily and weekly paclitaxel 50 mg/m2 plus carboplatin AUC 2. Consolidation gefitinib until progression was started after all toxicities were grade ≤2.ResultsAcute 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.ConclusionsSurvival 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.