Eli Lilly and Company announced that Paramount, its Phase III study evaluating Altima (pemetrexed for injection) in the continuation maintenance setting, met its primary endpoint of progression-free survival for patients with advanced non-squamous, non-small cell lung cancer (NSCLC).
Paramount is the second study to evaluate the use of Altima as a maintenance therapy in patients with advanced nonsquamous NSCLC, and the first study to evaluate the use of continuation maintenance with Altima following first-line Altima plus cisplatin therapy.
Results of this multicenter, double-blind trial demonstrated the median progression-free survival measured from randomization (after first-line treatment) was 3.9 months on the Altima arm as compared to 2.6 months on the placebo arm with a hazard ratio of 0.64.
The study showed that Altima continuation maintenance arm resulted in a 36% improvement of survival without disease worsening over the placebo arm. The maintenance disease control rate, measured at 6 weeks post-randomization, was 71.8% on the Altima arm and 59.6% on the placebo arm.
“Paramount demonstrated that an Altima continuation maintenance regimen—single-agent Altima following Altima plus cisplatin induction therapy—can improve progression-free survival in patients with the most common form of lung cancer,” said Allen S. Melemed, MD, MBA, Altima medical product development leader at Lilly Oncology.
A total of 939 patients with advanced nonsquamous NSCLC were enrolled in the study and received Altima (500 mg/m2 on day one of a 21-day cycle) in combination with cisplatin (75 mg/m2) induction therapy. Patients whose disease had not progressed during the Altima +cisplatin induction and had a performance status of 0-1 were randomized to receive Altima maintenance (500 mg/m2 on day one of a 21-day cycle) plus best supportive care or placebo plus best supportive care (n=180) until disease progression. All patients received vitamin B12, folic acid and dexamethasone.
Overall, the most serious grade 3/4 drug-related adverse events (AEs) were higher for those treated with Altima continuation maintenance versus placebo. The most commonly reported drug-related AEs observed on the Altima arm versus placebo were anemia fatigue and neutropenia. There was one potentially drug-related death on each arm. Discontinuations due to AEs were 5.3% with Altima and 3.3% with placebo.
The study was conducted in patients with advanced nonsquamous NSCLC because past studies have shown that advanced NSCLC patients with a nonsquamous histology (those with adenocarcinoma, large cell carcinoma, or other subtypes) experienced improved efficacy over the relative comparator arm in the trial (an increase in progression-free survival, as well as overall survival), when treated with an Altima regimen. Patients with advanced NSCLC with squamous cell histology were not included in the Paramount study as Altima has not shown to be effective in this patient population relative to the comparators in these previous trials.
Release Date: June 5, 2011
Source: Eli Lilly and Company
Filed Under: Drug Discovery