Eli Lilly and Company announced that PARAMOUNT, its Phase III study evaluating ALIMTA® (pemetrexed for injection) in the continuation maintenance setting, met its primary endpoint of progression-free survival, or the time a patient is alive without their disease worsening, for patients with a specific type of lung cancer called advanced nonsquamous non-small cell lung cancer (NSCLC). “Continuation maintenance” treatment is when one of the same medicines used in first-line treatment setting is continued as maintenance therapy in an effort to control the cancer.
Results from the study will be presented on Sunday, June 5 at 11:30 a.m. CDT during the Lung Cancer Oral Abstract Session (Abstract #CRA7510) at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Ill. Lilly will present overall survival results from PARAMOUNT at a medical meeting in the future.
PARAMOUNT is the second study to evaluate the use of ALIMTA as a maintenance therapy in patients with advanced nonsquamous NSCLC, and the first study to evaluate the use of continuation maintenance with ALIMTA(1) following first-line ALIMTA 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 ALIMTA arm as compared to 2.6 months on the placebo arm with a hazard ratio of 0.64. Said another way, the study showed that ALIMTA continuation maintenance arm resulted in a 36 percent improvement of survival without disease worsening over the placebo arm. The maintenance disease control rate, or the percentage of patients achieving either a response or stable disease first measured at 6 weeks post-randomization was 71.8 percent (2.8%/69.0%) on the ALIMTA arm and 59.6 percent (0.6%/59.0%) on the placebo arm.
“PARAMOUNT demonstrated that an ALIMTA continuation maintenance regimen—single-agent ALIMTA following ALIMTA plus cisplatin induction therapy—can improve progression-free survival in patients with the most common form of lung cancer,” said Allen S. Melemed, M.D., M.B.A., ALIMTA medical product development leader at Lilly Oncology. “This finding continues to validate the use of ALIMTA maintenance treatment for certain patients living with this devastating disease.”
A total of 939 patients with advanced nonsquamous NSCLC were enrolled in the study and received ALIMTA (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 ALIMTA+cisplatin induction and had a performance status of 0-1 (n=439) were randomized to receive ALIMTA maintenance (500 mg/m2 on day one of a 21-day cycle) plus best supportive care (n=359) 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 ALIMTA continuation maintenance versus placebo (9.2% vs. 0.6% laboratory and 8.9% vs. 4.4% non-laboratory). The most commonly reported drug-related AEs observed on the ALIMTA arm versus placebo were anemia (4.2% vs. 0.6%), fatigue (4.5% vs. 0.6%), and neutropenia (3.6% vs. 0%). There was one potentially drug-related death on each arm. Discontinuations due to AEs were 5.3 percent with ALIMTA and 3.3 percent 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 ALIMTA regimen.(1,2) Patients with advanced NSCLC with squamous cell histology were not included in the PARAMOUNT study as ALIMTA has not shown to be effective in this patient population relative to the comparators in these previous trials.