Randomized phase II study of paclitaxel/carboplatin intercalated with gefitinib compared to paclitaxel/carboplatin alone for chemotherapy-naïve non-small cell lung cancer in a clinically selected population excluding patients with non-smoking adenocarcinoma or mutated EGFR

BACKGROUND: Considering cell cycle dependent cytotoxicity, intercalation of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) may be a treatment option in non-small cell lung cancer (NSCLC). This randomized phase 2 study compared the efficacy of paclitaxel and carboplatin (PC) intercalated with gefitinib (G) versus PC alone in a selected, chemotherapy-naïve population of advanced NSCLC patients with a history of smoking or wild-type EGFR. METHODS: Eligible patients were chemotherapy-naïve advanced NSCLC patients with Eastern Cooperative Oncology Group performance status of 0—2. Non-smoking patients with adenocarcinoma or patients with activating EGFR mutation were excluded because they could benefit from gefitinib alone. Eligible patients were randomized to one of the following treatment arms: PCG, P 175 mg/m(2), and C AUC 5 administered intravenously on day 1 intercalated with G 250 mg orally on days 2 through 15 every 3 weeks for four cycles followed by G 250 mg orally until progressive disease; or PC, same dosing schedule for four cycles only. The primary endpoint was the objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity profile. RESULTS: A total of 90 patients participated in the study. The ORRs were 41.9 % (95 % confidence interval (CI) 27.0–57.9 %) for the PCG arm and 39.5 % (95 % CI 25.0–55.6 %) for the PC arm (P = 0.826). No differences in PFS (4.1 vs. 4.1 months, P = 0.781) or OS (9.3 vs. 10.5 months, P = 0.827) were observed between the PCG and PC arms. Safety analyses showed a similar incidence of drug-related grade 3/4 toxicity. Rash and pruritus were more frequent in the PCG than in the PC arm. CONCLUSIONS: PCG did not improve ORR, PFS, and OS compared to PC chemotherapy alone for NSCLC in a clinically selected population excluding non-smoking adenocarcinoma or mutated EGFR. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT01196234). Registration date is 08/09/2010.