ALIMTA CARBOPLATIN NOT GOOD ENOUGH FOR SCLC

J Clin Oncol. 2009 Aug 31. [Epub ahead of print]

Related Articles, LinkOut

Phase III Study of Pemetrexed Plus Carboplatin Compared With Etoposide Plus Carboplatin in Chemotherapy-Naive Patients With Extensive-Stage Small-Cell Lung Cancer.

Socinski MA, Smit EF, Lorigan P, Konduri K, Reck M, Szczesna A, Blakely J, Serwatowski P, Karaseva NA, Ciuleanu T, Jassem J, Dediu M, Hong S, Visseren-Grul C, Hanauske AR, Obasaju CK, Guba SC, Thatcher N.

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; Vrije University Medical Center, Amsterdam; Eli Lilly Netherlands, Utrecht, the Netherlands; Christie Hospital, Manchester, United Kingdom; US Oncology, Houston, TX; Hospital Grosshansdorf, Grosshansdorf; Department of Medicine and Medical Oncology, St Georg Hospital, Hamburg, Germany; Mazovian Center of Lung Diseases and Tuberculosis, Otwock; Sokolowski Specialist Hospital in Szczecin-Zdunowo; Medical University of Gdask, Gdask, Poland; The West Clinic, Memphis, TN; St Petersburg Oncology Center, St Petersburg, Russian Federation; Cancer Institute "Ion Chiricuta," Cluj-Napoca; "A. Trestioreanu" Oncology Institute, Bucharest University, Bucharest, Romania; Eli Lilly and Company, Indianapolis, IN.

PURPOSE: Following a phase II trial in which pemetrexed-platinum demonstrated similar activity to that of historical etoposide-platinum controls, a phase III study was conducted to compare pemetrexed-carboplatin with etoposide-carboplatin for the treatment of extensive-stage small-cell lung cancer (ES-SCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status of zero to 2 were randomly assigned to receive pemetrexed-carboplatin (pemetrexed 500 mg/m(2) on day 1; carboplatin at area under the serum concentration-time curve [AUC] 5 on day 1) or etoposide-carboplatin (etoposide 100 mg/m(2) on days 1 through 3; carboplatin AUC 5 on day 1) every 3 weeks for up to six cycles. The primary objective of the study was noninferiority of pemetrexed-carboplatin overall survival with a 15% margin. RESULTS: Accrual was terminated with 908 of 1,820 patients enrolled after results of a planned interim analysis. In the final analysis, pemetrexed-carboplatin was inferior to etoposide-carboplatin for overall survival (median, 8.1 v 10.6 months; hazard ratio [HR],1.56; 95% CI, 1.27 to 1.92; log-rank P < .01) and progression-free survival (median, 3.8 v 5.4 months; HR, 1.85; 95% CI, 1.58 to 2.17; log-rank P < .01). Objective response rates were also significantly lower for pemetrexed-carboplatin (31% v 52%; P < .001). Pemetrexed-carboplatin had lower grade 3 to 4 neutropenia, febrile neutropenia, and leukopenia than etoposide-carboplatin; grade 3 to 4 thrombocytopenia was comparable between arms and anemia was higher in the pemetrexed-carboplatin arm. CONCLUSION: Pemetrexed-carboplatin is inferior for the treatment of ES-SCLC. Planned translational research and pharmacogenomic analyses of tumor and blood samples may help explain the study results and provide insight into new treatment strategies.