Nonsquamous non-small cell lung cancer: PRONOUNCE study does not achieve primary superiority endpoint for Alimta
The results from its PRONOUNCE trial of Alimta ( Pemetrexed for injection ) for treatment of nonsquamous non-small cell lung cancer ( NSCLC ) have been presented at the American Society of Clinical Oncology ( ASCO ) annual meeting.
The PRONOUNCE trial compared a 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.
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/m2 and Carboplatin, AUC=6; PacCBev regimen: Paclitaxel, 200 mg/m2, 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 progression-free survival, overall survival, 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% 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; p=0.176 ). Progression-free survival and overall survival had HR=1.06, p=0.610, and HR=1.07, 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 ).
There were no unexpected toxicities in either regimen in the PRONOUNCE trial. Results from the PemC arm saw significantly more drug-related grade 3/4 anemia, or low red blood cells ( 18.7% vs. 5.4% ), and thrombocytopenia, which is a decrease in blood platelets ( 24.0% vs 9.6% ).
Results from the PacCBev arm saw significantly more grade 3/4 neutropenia, which is low white blood cell count ( 48.8% vs 24.6% ), grade 1-3 sensory neuropathy, which is sensory alteration in nerves that ranges from mild tingling to impaired functioning and pain ( 32.5% vs 8.2% ), and grade 1/2 alopecia or hair loss ( 28.3% vs 8.2% ). No difference in grade 3/4 fatigue was seen between the treatment arms in this trial ( 6.4% in the PemC arm vs. 5.4% in the PacCBev arm ). Toxicity profiles were otherwise consistent with the known safety profiles of each therapy. ( Xagena )
Source: Lilly, 2013
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