Phase III Trial Comparing Oral S-1 Plus Carboplatin With Paclitaxel Plus Carboplatin in Chemotherapy-Naïve Patients With Advanced Non–Small-Cell Lung Cancer: Results of a West Japan Oncology Group Study

• Published in: Journal of clinical oncology Vol. 28; no. 36; pp. 5240 - 5246
• Main Authors: OKAMOTO, Isamu, YOSHIOKA, Hiroshige, KUDOH, Shinzoh, SATOUCHI, Miyako, IKEDA, Norihiko, IWAMOTO, Yasuo, SAWA, Toshiyuki, MIYAZAKI, Masaki, TAMURA, Kenji, KURATA, Takayasu, FUKUOKA, Masahiro, NAKAGAWA, Kazuhiko, MORITA, Satoshi, ANDO, Masahiko, TAKEDA, Koji, SETO, Takashi, YAMAMOTO, Nobuyuki, SAKA, Hideo, ASAMI, Kazuhiro, HIRASHIMA, Tomonori
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20-12-2010
• Subjects: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Drug Combinations; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Male; Medical sciences; Middle Aged; Oxonic Acid - administration & dosage; Paclitaxel - administration & dosage; Pneumology; Survival Analysis; Tegafur - administration & dosage; Tumors; Tumors of the respiratory system and mediastinum; Asia; Japan; Antineoplastic agent; Phase III trial; Human; Lung disease; Respiratory disease; Lung cancer; Malignant tumor; non-small cell lung carcinoma; Chemotherapy; Cancerology; Treatment; Taxane derivatives; Paclitaxel; Carboplatin; Bronchus disease; Advanced stage; Antimitotic; Comparative study; Cancer; Platinum II Complexes
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2010.31.0326

The primary goal of this open-label, multicenter, randomized phase III trial was to determine whether treatment with carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with carboplatin plus paclitaxel with regard to overall survival (OS) in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC).
A total of 564 patients were randomly assigned to receive either carboplatin (area under the curve, 5) on day 1 plus oral S-1 (40 mg/m2 twice per day) on days 1 to 14 or carboplatin (area under the curve, 6) plus paclitaxel (200 mg/m2) on day 1 every 21 days.
At the planned interim analysis, with a total of 268 death events available, the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of carboplatin and S-1 compared with carboplatin and paclitaxel was confirmed for OS (hazard ratio, 0.928; 99.2% CI, 0.671 to 1.283). Median OS was 15.2 months in the carboplatin and S-1 arm and 13.3 months in the carboplatin and paclitaxel arm, with 1-year survival rates of 57.3% and 55.5%, respectively. Rates of leukopenia or neutropenia of grade 3/4, febrile neutropenia, alopecia, and neuropathy were more frequent in the carboplatin and paclitaxel arm, whereas thrombocytopenia, nausea, vomiting, and diarrhea were more common in the carboplatin and S-1 arm. The carboplatin and S-1 arm had significantly more dose delays than the carboplatin and paclitaxel arm.
Oral S-1 with carboplatin was noninferior in terms of OS compared with carboplatin and paclitaxel in patients with advanced NSCLC, and is thus a valid treatment option.