Abstract A77: Randomized phase II study comparing paclitaxel/carboplatin intercalated with gefitinib to paclitaxel/carboplatin alone for chemotherapy-naive non-small cell lung cancer patients either with history of smoking or with wild-type EGFR.
Authors: Lee Dae Ho , Kim Jeong Eun , Choi Yoon J. , Choi Chang Min , Lee Jung-Shin , Kim Sang-We 
Published: August 2014

Abstract
Background: There are preclinical and clinical reports of schedule-dependent synergism or antagonism when combining cytotoxic chemotherapy and EGFR inhibitor therapy in non-small cell lung cancer (NSCLC). While antagonism was associated with EGFR inhibitor-induced G1-phase blockade protecting tumor cells from chemotherapy cytotoxicity, appropriate scheduling of EGFR inhibitor with chemotherapy might produce additive or synergistic tumor growth inhibition. This randomized phase 2 study compared the efficacy of paclitaxel-carboplatin (PC) intercalated with gefitinib (G) versus PC alone, as a first-line treatment in a selected population of advanced NSCLC patients either with history of smoking or with wild-type EGFR.
Methods: Eligible patients were chemotherapy-naive advanced NSCLC patients with good ECOG PS of 0 or 1. 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 either one of the treatments; PCG arm, P 175 mg/m2 and C AUC 5 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 arm, P 175 mg/m2 and C AUC 5 on day 1 every 3 weeks for four cycles only without maintenance therapy. The primary endpoint was 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 (male 85.6%; median age, 59; adenocarcinoma 63%; smoker 90%; and wild-type EGFR 24%, unknown EGFR status 76%) participated into the study. The ORR was 40.9% (95% CI 27.3-56.8%) and 37.0% (95% CI 23.8-51.2%) for the two arms (p=0.701). There was also no difference in terms of PFS (the median PFS; PCG arm, 4.1 mo vs. PC arm 4.1 mo, HR=0.941 [95%CI: 0.61-1.45], p=0.781) and OS (the median OS; PCG arm 9.3 mo vs. PC arm10.5 mo, HR=0.95 [95% CI: 0.58-1.54], p=0.827). Safety analyses showed a similar incidence of drug-related grade 3/4 toxicity in PCG arm (20.9%) compared with in PC arm (23.3%). G1/2 rash and diarrhea was more frequent in PCG arm (58% vs.9% and 14% vs. 7%, respectively).
Conclusion: Paclitaxel-carboplatin chemotherapy intercalated with gefitinib did not improved ORR, PFS, and OS compared to PC chemotherapy alone in this selected population of advanced NSCLC patients either with history of smoking or with wild-type EGFR.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A77.
Citation Format: Dae Ho Lee, Jeong Eun Kim, Yoon Ji Choi, Chang Min Choi, Jung-Shin Lee, Sang-We Kim. Randomized phase II study comparing paclitaxel/carboplatin intercalated with gefitinib to paclitaxel/carboplatin alone for chemotherapy-naive non-small cell lung cancer patients either with history of smoking or with wild-type EGFR. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A77.