A phase III study of pemetrexed vs docetaxel in patients with recurrent non-small cell lung cancer (NSCLC) who were previously treated with chemotherapy.

Category: Non-Small-Cell Lung Cancer

Authors: N. H. Hanna, F. A. Shepherd, R. Rosell, J. R. Pereira, F. De Marinis, F. Fossella, L. Kayitalire, S. Paul, L. H. Einhorn, P. A. Bunn; Indiana University, Indianapolis, IN; Princess Margaret Hospital, Toronto, ON, Canada; Hospital Germans Trias: Pujol, Badalona, Spain; Instituto Arnaldo Vieira de Carvalho, San Paulo, Brazil; Pneumological Hosp 'C Forlanini', Rome, Italy; MD Anderson Cancer Ctr, Houston, TX; Eli Lilly and Co, Indianapolis, IN; University of Colorado, Denver, CO

Abstract: Docetaxel is now the standard second-line treatment for NSCLC for patients (pts) with a good performance status based upon improved outcome compared to ifosfamide or vinorelbine or best supportive care in 2 randomized phase III studies. Pemetrexed, a novel multitargeted antifolate that inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT), has shown clinical activity against NSCLC in phase II studies, as initial or second-line therapy. We report the results of a multi-center, randomized, phase III comparison of pemetrexed vs docetaxel in previously treated pts with recurrent NSCLC. Pts (n=571) were randomized from 3/01 to 2/02, to receive either pemetrexed (500 mg/m² IV infusion), supplemented with vitamin B12 injections, folic acid and dexamethasone or docetaxel (75 mg/m² IV infusion) with dexamethasone on day 1 of 21-day cycles. The primary objective was to compare overall survival and secondary endpoints were time to event measures, response rate, toxicity, and quality of life. There were 411 males, 160 females, median age 58 years (range 22 -87), ECOG PS 0/1 (87%) or 2 (12%), recurrent stage IV disease (75%), stage III (25%). 95% had 1 prior chemotherapy regimen and 5% had 2 regimens (neoadjuvant +adjuvant =1 regimen, only 1 metastatic therapy allowed). 90% had prior platinum therapy and 28% had prior taxanes. 2241 total cycles were given, (median 3, range 0-20). Ten months after the last pt was randomized, 299 (52%) of 571 patients have died. Grade 3/4 toxicities include neutropenia (40%), neutropenic fever (7%), anemia (6%), thrombocytopenia (2%), fatigue (5%), nausea (2%), anorexia (2%), diarrhea (1%), neuropathy (1%) and hypersensitivity (<1%). The confirmed response rate for all pts treated was 7.9% and stable disease was observed in an additional 43% of pts. The median time to disease progression is 3 months (18% censored). Survival data are not mature. Data are expected to mature January 2003, and the final comparison results will be available at the time of the 2003 ASCO meeting. Supported by Eli Lilly and Co.