PRONOUNCE Study Does Not Achieve Primary Superiority Endpoint For ALIMTA® (pemetrexed For Injection), Similar PFS And OS Results Were Observed Between The Two Drug And The Three Drug Regimens In The Treatment Of NSCLC
CHICAGO, June 3, 2013 /PRNewswire/ -- Eli Lilly and Company (NYSE:LLY) announced results from its PRONOUNCE trial of ALIMTA® (pemetrexed for injection) for treatment of nonsquamous non-small cell lung cancer (NSCLC) that was presented today at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Ill. The PRONOUNCE trial compared an ALIMTA (pemetrexed), carboplatin doublet regimen to a paclitaxel, carboplatin and bevacizumab triplet regimen. The study did not achieve its primary superiority endpoint of improved progression-free survival without grade four adverse events (G4PFS). No significant difference was observed between the treatment arms for secondary endpoints of progression-free survival (PFS), overall survival, overall response rate and disease control rate. Toxicity profiles observed in the trial were consistent with the known safety profiles of each therapy. "The history of ALIMTA clinical evaluation – from histology to its use in the maintenance therapy paradigm – encourages us to explore new avenues to determine if we can improve patient outcomes," said Richard Gaynor, M.D., vice president of product development and medical affairs for Lilly Oncology. "These data give us additional insights that further inform the vast body of ALIMTA clinical data." The safety and efficacy profile for ALIMTA has been the subject of Lilly-sponsored studies involving an estimated 32,500 patients over the span of almost 20 years 1. About PRONOUNCE (Abstract #LBA8003)PRONOUNCE is a randomized, open-label Phase III superiority study of first-line chemotherapy pemetrexed plus carboplatin (PemC regimen) followed by maintenance pemetrexed, compared to paclitaxel plus carboplatin plus bevacizumab (PacCBev regimen) followed by maintenance bevacizumab in patients with advanced nonsquamous NSCLC conducted in the U.S. Patients were randomized (1:1) to the PemC regimen (n=182) or PacCBev regimen (n=179). Patients received four cycles of induction PemC regimen: pemetrexed, 500 mg/m 2 and carboplatin, AUC=6; PacCBev regimen: paclitaxel, 200 mg/m 2, carboplatin, AUC=6 and bevacizumab, 15 mg/kg followed by pemetrexed (PemC regimen) or bevacizumab (PacCBev regimen) maintenance therapy in the absence of progressive disease or discontinuation. The primary endpoint, G4PFS was measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. 2 Secondary endpoints were PFS, overall survival (OS), overall response rate (ORR), and disease control rate (DCR). The study was powered for G4PFS. Assuming a hazard ratio (HR) of 0.75, there was 80 percent power to detect superiority of the PemC regimen over the PacCBev regimen with a two-sided type one error of 0.10. The median G4PFS was 3.91 months on the PemC regimen vs. 2.86 months on the PacCBev regimen (HR=0.85, 90% CI 0.7, 1.04, p=0.176). PFS and OS had HR=1.06 (95% CI 0.84, 1.35), p=0.610, and HR=1.07 (95% CI 0.83, 1.36), p=0.615, respectively. The ORR was 23.6% (PemC regimen) and 27.4% (PacCBev regimen) and the DCR was 59.9% (PemC regimen) and 57.0% (PacCBev regimen).