1326 - Phase II Trial of Carboplatin and Pemetrexed as First-Line Chemotherapy for Non-Squamous Non-Small Cell Lung Cancer and Correlation Between the Efficacy/Toxicity and Genetic Polymorphisms Associated with Pemetrexed Metabolism: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0902

Abstract

ABSTRACT Background The importance of biomarkers is increasing in individualized treatment strategy for cancer patients (pts). We evaluated the efficacy and safety of carboplatin (CBDCA) and pemetrexed (PEM) in Japanese pts with non-squamous non-small cell lung cancer (NSCLC), and single nucleotide polymorphisms (SNPs) associated with PEM metabolism were also analyzed to investigate their relationship with efficacy or toxicity. Patients and methods Eligible pts had a performance status 0 or 1, aged from 20 to 74 years, chemotherapy-naive stage IIIB/IV non-squamous NSCLC, and adequate organ function. Pts received CBDCA at a dose targeting an area under the concentration-time curve of 5 and 500 mg/m2 PEM every 3 weeks. More than 3 cycles was considered as completion of treatment. Peripheral blood was drawn for SNPs analyses of thymidylate synthase gene (TS) and methylenetetrahydrofolate reductase gene (MTHFR) in pts with consent for the biomarker study. Results Forty-one pts (28 men, 13 women; median age 63 years, range 43 - 73), with 39 adenocarcinomas and 2 large cell carcinomas, were enrolled and SNPs were analyzed in 37 pts. The median follow-up time was 16.1 months and the median number of treatment cycle was 4 (range 1 - 6). The completion rate was 80.5% (33 pts). All pts were assessable for response; the overall response rate (RR) was 36.6% and disease control rate (DCR) was 85.4%. Median progression-free survival (PFS) and overall survival (OS) were 4.6 months (138 days: 95%C.I.; 107-168) and 16.1 months (483 days: 95%C.I.; 180-786), respectively. Grade 3 or 4 hematologic toxicities included anemia (34.1%), neutropenia (29.3%), leukopenia (19.5%) and thrombocytopenia (17.1%). Grade 3 or 4 non-hematologic toxicities included anorexia (7.3%) and nausea (4.9%). No treatment-related death was observed. Although the SNPs had no relation to PFS, OS, RR nor hematologic toxicity, the variable number of tandem repeat (VNTR) of the TS significantly correlated with anemia (p = 0.047) and thrombocytopenia (p = 0.038). Conclusion The efficacy of this regimen seems even better than previously reported, and with acceptable toxicities. VNTR of the TS has the possibility of being a predictive factor of anemia and thrombocytopenia for this regimen. Disclosure All authors have declared no conflicts of interest.