455PA phase II trial of carboplatin plus S-1 for elderly patients with advanced non-small cell lung cancer with wild-type EGFR: The Okayama Lung Cancer Study Group Trial 1202 (OLCSG1202)

Background: S-1 is an oral fluoropyrimidine-based combination of tegafur, gimeracil, and oteracil potassium. Although the combination of S-1 with carboplatin is a first-line chemotherapy regimen for advanced non-small-cell lung cancer (NSCLC), the efficacy and safety of the regimen in the elderly remain unknown. Methods: The patient inclusion criteria were previously untreated advanced NSCLC, wild-type EGFR, aged 70 years or more, and a PS of 0–2. The patients received oral S-1 (40 mg/m2, twice daily) for 2 weeks and carboplatin (AUC 5) on day 1 every 4 weeks as induction treatment. After four induction cycles, S-1 alone (40 mg/m2, twice daily) was administered for 2 weeks every 4 weeks as a maintenance therapy until disease progression. The primary endpoint was the overall response rate (ORR), which was expected to exceed 20%, and the secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the toxicity profile. The associations between clinical outcomes and expression of genes such as thymidylate synthase and thymidine phosphorylase in the tumors were evaluated. Results: Thirty-three patients were enrolled between March 2013 and June 2015. The median age was 78 (range 70–89) years, and 51.5% had a PS of 0. The ORR was 30.3% (95% confidence interval (CI): 14.6–46.0) and the DCR 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 treatmentrelated death due to aspiration pneumonia following febrile neutropenia. The median PFS and OS were 134 days (95% CI: 79–173) and 479 days (95% CI: 250–571), respectively. Low thymidine phosphorylase expression was associated with the DCR (P < 0.01). Conclusions: This study met the predesigned primary endpoint, and the regimen seems to be a favorable treatment option. Clinical trial indentification: University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR): UMIN000009345. Legal entity responsible for the study: Okayama Lung Cancer Study Group (OLCSG) Funding: None Disclosure: A. Bessho: Speakers Bureau : AstraZeneca K.K. Bristol-Myers Squibb Japan ONO PHARMACEUTICAL CO., LTD. Chugai Pharmaceutical Co., Ltd. TAIHO PHARMACEUTICAL CO., LTD. KYORIN Pharmaceutical Co., Ltd. Pfizer Japan Inc. Eli Lilly Japan K.K. Nippon Boehringer Ingelheim Co., Ltd. S. Kuyama: Speakers Bureau AstraZeneca K.K. Bristol-Myers Squibb Japan Chugai Pharmaceutical Co., Ltd. Nippon Boehringer Ingelheim Co., Ltd. D. Harada: Speakers Bureau ONO PHARMACEUTICAL CO., LTD. Bristol-Myers Squibb Company Yakult Honsha Co., Ltd. Kyowa Hakko Kirin Co., Ltd. N. Nogami: Speakers Bureau AstraZeneca K.K. Bristol-Myers Squibb Japan ONO PHARMACEUTICAL CO., LTD. Chugai Pharmaceutical Co., Ltd. TAIHO PHARMACEUTICAL CO., LTD. Eli Lilly Japan K.K. Nippon Boehringer Ingelheim Co., Ltd. N. Fujimoto: Speakers bureaus ONO PHARMACEUTICAL CO., LTD. MSD K.K. K. Hotta: Speakers Bureau AstraZeneca K.K. Bristol-Myers Squibb Japan ONO PHARMACEUTICAL CO., LTD. Chugai Pharmaceutical Co., Ltd. TAIHO PHARMACEUTICAL CO., LTD. Pfizer Japan Inc. Eli Lilly Japan K.K. Nippon Boehringer Ingelheim Co., Ltd. Research Funding MSD, Chugai, Lilly, ONO, BMS, Novartis, N. Takigawa: Reseach funding: Boehringer Ingelheim, Chugai Pharma, Pfizer, AstraZeneca, Taiho Pharmaceutical, Kyowa-Hakko Kirin, Nihonkayaku, Ono Pharmaceutical Honoraria: Chugai Pharma, Pfizer, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Kyowa-Hakko Kirin, Daiichi-Sankyo, Eisai, Ono Pharmaceutical, MSD, Eli-Lilly Japan, K. Kiura: Speakers Bureau AstraZeneca K.K. Bristol-Myers Squibb Japan ONO PHARMACEUTICAL CO., LTD. Chugai Pharmaceutical Co., Ltd. TAIHO PHARMACEUTICAL CO., LTD. Pfizer Japan Inc. Eli Lilly Japan K.K. Nippon Boehringer Ingelheim Co., Ltd. All other authors have declared no conflicts of interest.