A Phase Ii Trial Of Carboplatin Plus S-1 For Elderly Patients With Advanced Non-Small Cell Lung Cancer With Wild Type Egfr (Olcsg1202)

e20614 Background: S-1 is an oral fluoropyrimidine anticancer agent that combines tegafur, gimeracil, and oteracil potassium. Two phase III trials in advanced non-small cell lung cancer (NSCLC) showed the non-inferiority of combination of S-1 with carboplatin or cisplatin compared with standard platinum doublet chemotherapy. Although the S-1/platinum is one of the first line combinations for advanced NSCLC, efficacy and safety of the regimen in the elderly remain unknown. Methods: Patients were required to be previously untreated advanced NSCLC with wild-type EGFR, aged 70 or more, PS of 0-2. They received oral S-1 (40 mg/m 2 , twice daily) for 2 weeks and carboplatin (AUC 5 on day 1) every 4 weeks as an induction treatment. After 4 cycles of the induction, S-1 alone (40 mg/m 2 , twice daily for 2 weeks) was administrated every 4 weeks as a maintenance therapy until PD. Primary endpoint was overall response rate (ORR), which was expected more than 20%, and secondary endpoints included disease control rate (DCR), PFS, OS, and toxicity profile. The association between clinical outcomes and gene expressions including thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase, VEGF and ERCC1 in tumors was evaluated. Results: Thirty-three patients were enrolled between March 2013 and June 2015. Median age was 78 years old (range: 70 – 89), and 51.5% had a PS of 0. ORR was 30.3% (95% CI: 14.6 – 46.0%) and DCR was 57.6% (95% CI: 40.7 – 74.4%). Grade 3/4 toxicities included thrombocytopenia (42.4%), neutropenia (33.3%) and anemia (27.3%). There was one treatment-related death due to aspiration pneumonia following febrile neutropenia. Median PFS and OS times were 134 days (95% CI: 79 – 173) and 479 days (95% CI: 250 – 571), respectively. Low thymidine phosphorylase expression was associated with DCR (P < 0.01). Conclusions: Carboplatin plus S-1 showed preferable efficacy and tolerable toxicity for elderly with NSCLC. (Clinical trial number: UMIN000009345) Clinical trial information: 9345.