1381PDGefitinib with or without pemetrexed in nonsquamous (NS) non-small cell lung cancer (NSCLC) with EGFR mutation (mut): Final overall survival (OS) results from a randomized phase II study

Background: The combination of pemetrexed (P)-based chemotherapy with EGFR-tyrosine kinase inhibitors (TKI) has resulted in improved efficacy vs EGFR-TKI alone for treatment (tx) of advanced NSCLC with EGFR-mut. The objective of this disclosure is to report OS, updated progression-free survival (PFS), and safety of P+Gefitinib (G) vs G alone in patients (pts) with advanced NS NSCLC with EGFR-mut. Methods: Primary outcome of this phase II, multicenter, randomized study has been published. Pts were randomly assigned to receive P+G or G alone at a ratio of 2:1 (P, 500 mg/m2 on day (d) 1 of every 21-d cycle; G, 250 mg/d). Primary and secondary objectives were PFS and OS, respectively. Adjusted Cox regression model was used to estimate adjusted HR for difference between tx arms. Results: 191 pts were randomized to P+G (n = 126) or G (n = 65). Majority of the pts were female (P+G [65%], G [63%]), non-smokers (P+G [64%], G [72%]), and had stage IV disease (P+G [83%], G [88%]). At final database lock, 111 (58.1%) pts had OS events (death; P+G [n = 72], G [n = 39]) while 164 pts had PFS events (progression or death; P+G [n = 102], G [n = 62]). OS was numerically higher in pts receiving P+G (43.4 months; 95% CI, 33.4-50.8) vs G alone (36.8 months; 95% CI, 26.7-42.6); adjusted HR, 0.77; 95% CI, 0.5-1.2; one-sided P = 0.105. In this updated analysis, PFS continued to be prolonged in P+G group (16.2 months; 95% CI, 12.6-18.7) vs G alone (11.07 months; 95% CI, 9.7-13.8); adjusted HR, 0.67; 95% CI, 0.5-0.9; one-sided P = 0.009. A higher % of pts in G arm received post-discontinuation systemic tx, (P+G, 68.3%; G, 78.5%), including 37 (56.9%) pts who received P. The most common drug related all grade adverse events (AEs) reported for P+G vs G were rash (53.2% vs 55.4%), diarrhea (45.2% vs 47.7%), and pruritus (35.7% vs 32.3%). Thirteen pts reported serious AEs (SAEs; P+G [n = 12, G [n = 1]); 1 pt in each arm discontinued due to SAEs. Two deaths were reported in P+G arm due to AEs. Conclusions: Combination of P+G demonstrated numerically higher OS compared with G alone in tx-naïve pts with EGFR-mut advanced NS NSCLC. PFS was significantly prolonged with P+G and more pts experienced AEs in P+G vs G arm. Clinical trial identification: NCT01469000. Editorial acknowledgement: The authors acknowledge Vinay Kumar Ranka for writing assistance on this abstract. Legal entity responsible for the study: Eli Lilly and Company. Funding: Eli Lilly and Company. Disclosure: J.C.-H. Yang: Personal fees: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceuticals, Daiichi Sankyo, AstraZeneca, Hansoh Pharmaceuticals, Takeda Pharmaceuticals, outside the submitted work. H. Murakami: Grants and personal fees: AstraZeneca; personal fees: Lilly Japan, Chugai Pharma, Boehringer Ingelheim, Pfizer, Taiho Pharmaceutical, Novartis, Bristol-Myers Squibb Japan, Ono Pharmaceutical, Merck Sharp & Dohme, outside the submitted work. K. Nakagawa: Grants and personal fees: AstraZeneca, during the conduct of the study; Grants and personal fees: MSD K.K., Astellas Pharma Inc, Novartis Pharma K.K., Chugai Pharmaceutical Co.,Ltd., Eli Lilly Japan K.K., Taiho Pharmaceutical Co.,Ltd, Ono Pharmaceutical Co., Ltd; Grants from A2 Healthcare Corp, inVentiv Health Japan, Daiichi Sankyo Co., Ltd., AbbVie Inc., Quintiles Inc., Icon Japan K.K., Takeda Pharmaceutical Co.,Ltd., EP-CRSU CO., LTD., Gritsone Oncology Inc., Linical Co.,Ltd., Eisai Co., Ltd., Parexel International Corp.; Personal fees: Clinical Trial Co., Ltd, Nippon Boehringer Ingelheim Co. Ltd., SymBio Pharmaceuticals Limited. X. Wnag: Employee: Eli Lilly and Company. S. Enatsu, T. Puri, M. Orlando: Other: Eli Lilly, outside the submitted work. All other authors have declared no conflicts of interest.