Comparison of pemetrexed plus cisplatin with other first-line doublets in advanced non-small cell lung cancer (NSCLC): a combined analysis of three phase 3 trials.

Abstract

INTRODUCTION:

In a first-line study of advanced NSCLC, pemetrexed-cisplatin was more effective among patients with adenocarcinoma and large-cell carcinoma compared with gemcitabine-cisplatin (median survival of 11.8 versus 10.4 months, P=.005), while survival with pemetrexed-cisplatin was shorter than with gemcitabine-cisplatin in patients with squamous cell carcinoma. The comparability of pemetrexed-cisplatin to other commonly used regimens within histology subgroups needs to be explored.

METHODS:

This retrospective analysis combined the patient-level data from three phase 3 randomized controlled trials that compared the efficacy of different third generation platinum- and non-platinum based doublets. Unadjusted median survival times and Cox covariate-adjusted treatment hazard ratio (HR) estimates were calculated. Overall results and subgroups by histological type were reported.

RESULTS:

This combined analysis consisted of 3467 patients. In the overall analysis, adjusted HRs favored pemetrexed (HR <1.0) to each of the other 5 regimens, though none of these HRs were statistically significant. Among patients with non-squamous histology, pemetrexed-cisplatin produced favorable HRs to each of the other regimens, achieving statistical significance when compared with vinorelbine-cisplatin (HR=0.67; 95% confidence intervals [CI]: 0.50, 0.91) and gemcitabine-cisplatin (HR=0.85; 95% CI: 0.75, 0.97). Among patients with squamous histology, 4 of the 5 comparison regimens produced favorable HRs (HR >1.0) when compared with pemetrexed-cisplatin, with only the comparison with gemcitabine-cisplatin achieving statistical significance (HR=1.23; 95% CI: 1.00, 1.51).

CONCLUSION:

In the absence of randomized clinical trial data comparing pemetrexed-cisplatin to commonly used doublets in advanced NSCLC other than gemcitabine-cisplatin, this combined analysis of multiple trials provides estimates for such comparisons.

• Authors: Joseph Treat, Giorgio V Scagliotti, Guangbin Peng, Matthew J Monberg, Coleman K Obasaju, Mark A Socinski
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 76 Issue 2 Pg. 222-7 (May 2012) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 22115704 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Glutamates
• Organoplatinum Compounds
• Pemetrexed
• Deoxycytidine
• Vinblastine
• Guanine
• Cisplatin
• Vinorelbine
• Gemcitabine

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Cisplatin (administration & dosage)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Female
• Glutamates (administration & dosage)
• Guanine (administration & dosage, analogs & derivatives)
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Organoplatinum Compounds (administration & dosage)
• Pemetrexed
• Retrospective Studies
• Vinblastine (administration & dosage, analogs & derivatives)
• Vinorelbine
• Gemcitabine