Lilly announces final results from ALIMTA Phase III study on NSCLC

Final results from PARAMOUNT, a Phase III study of ALIMTA^® (pemetrexed for injection) in the continuation maintenance setting, demonstrated improved overall survival in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) treated with ALIMTA continuation maintenance, according to data announced today by Eli Lilly and Company (NYSE: LLY). PARAMOUNT results will be presented on Monday, June 4, at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Ill.

Representing a paradigm shift in the treatment of lung cancer, "continuation maintenance" treatment is when one of the same medicines used in the first-line treatment setting is continued as maintenance therapy in an ongoing effort to control the cancer. Prior to the use of maintenance treatment, physicians typically treated a patient with four to six cycles of chemotherapy and then waited until the disease returned or worsened before treating it again. In PARAMOUNT, ALIMTA was prescribed in combination with cisplatin induction therapy immediately followed by maintenance ALIMTA and best supportive care.

PARAMOUNT builds upon previous studies evaluating the use of ALIMTA as a first-line therapy with cisplatin, as well as ALIMTA as a maintenance therapy (following non-ALIMTA first-line agents) in patients with advanced nonsquamous NSCLC. However, PARAMOUNT is the first study that evaluated both the use of ALIMTA plus cisplatin therapy followed immediately by the use of ALIMTA in the continuation maintenance setting. At ASCO 2011, the primary progression-free survival results of PARAMOUNT were presented and showed that ALIMTA continuation maintenance improved progression-free survival, or the time a patient is alive without their disease worsening.

Final results of this multicenter, double-blind, placebo-controlled trial demonstrated a statistically significant 22 percent reduction in the risk of death (HR=0.78). Patients achieved a median overall survival of 13.9 months from randomization (16.9 months from start of induction) on the ALIMTA continuation maintenance arm compared to 11.0 months from randomization (14.0 months from start of induction) on the placebo arm.

"The ALIMTA PARAMOUNT study is the first to show a survival benefit in continuation maintenance – answering an important question for physicians treating patients with this type of lung cancer," said Allen S. Melemed, M.D., M.B.A., a senior medical director with Lilly Oncology.

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=539) were randomized two-to-one 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. Of randomized patients, 44.9% had either a complete response or partial response and 51.9% had a response of stable disease to ALIMTA plus cisplatin induction treatment. 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 (12.5% vs. 0.6% laboratory and 11.4% vs. 4.4% non-laboratory). The most commonly reported grade 3/4 drug-related AEs observed on the ALIMTA arm versus placebo were anemia (6.4% vs. 0.6%), fatigue (4.7% vs. 1.1%), and neutropenia (5.8% vs. 0%). There was one potentially drug-related death on the ALIMTA arm and two on the placebo arm. Discontinuations due to AEs were 18% with ALIMTA and 7% with placebo.

PARAMOUNT was conducted specifically in patients with advanced nonsquamous NSCLC because past studies have shown that advanced NSCLC patients with a nonsquamous histology (those with the subtypes of adenocarcinoma, large cell carcinoma or "other" histologies) experienced improved efficacy over the relative comparator arm in the trial, when treated with an ALIMTA regimen. 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.