1404 - Gefitinib 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.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Editorial Acknowledgement

The authors acknowledge Vinay Kumar Ranka for writing assistance on this abstract.

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.