Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer

G.V. Scagliotti, P. Parikh, J. von Pawel, B. Biesma, J. Vansteenkiste, C. Manegold, P. Serwatowski, U. Gatzemeier, R. Digumarti, M. Zukin, J.S. Lee, A. Mellemgaard, K. Park, S. Patil, J. Rolski, T. Goksel, F. de Marinis, L. Simms, K.P. Sugarman, D. Gandara

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Abstract

Purpose Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. Patients and Methods This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m(2) on day 1 and gemcitabine 1,250 mg/m(2) on days 1 and 8 (n = 863) or cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 (n = 862) every 3 weeks for up to six cycles. Results Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/ gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/ pemetrexed versus cisplatin/ gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/ gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P <= .001); febrile neutropenia (P = .002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4 nausea (P = .004) was more common. Conclusion In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type
Udgivelsesdato: 2008/7/20
OriginalsprogEngelsk
TidsskriftJournal of Clinical Oncology
Vol/bind26
Udgave nummer21
Sider (fra-til)3543-3551
Antal sider8
ISSN0732-183X
StatusUdgivet - 2008

Bibliografisk note

Times Cited: 2Proceedings PaperEnglishScagliotti, G. VUniv Turin, S Luigi Hosp, Dept Clin & Biol Sci, Reg Gonzole 10, I-10043 Turin, ItalyCited References Count: 35331ZFAMER SOC CLINICAL ONCOLOGY2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USAALEXANDRIA

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