Article

Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non-Small-Cell Lung Cancer

University of California, Davis, Davis, California, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 07/2008; 26(21):3543-51. DOI: 10.1200/JCO.2007.15.0375
Source: PubMed

ABSTRACT 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.
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.
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 <or= .001); febrile neutropenia (P = .002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4 nausea (P = .004) was more common.
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.

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    • "Several European studies also found higher frequencies than our study, but (unconscious) selection for testing based on clinical factors may have played a role in these findings. As a reminder and for comparison, in the hitherto largest – predominantly European – study in advanced NSCLC [2], there were 30% female patients and 14% never-smokers. In the more recent Spanish findings in the context of a randomised controlled trial, occurrence of exon 19 or 21 mutations was 16.6% [19]. "
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