PARAMOUNT: Phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) versus placebo plus BSC immediately following induction treatment with pem plus cisplatin for advanced nonsquamous non-small cell lung cancer (NSCLC).

Abstract

CRA7510 Background: The PARAMOUNT trial investigated whether pem continuation maintenance therapy improves progression-free survival (PFS) after pem-cisplatin induction therapy in patients (pts) with advanced nonsquamous NSCLC. Methods: In this double-blind, placebo-controlled trial, 939 pts participated in the induction phase, specified as four cycles of induction pem (500 mg/m 2 ) and cisplatin (75 mg/m 2 ) on day 1 of a 21-day cycle. Pts who had not progressed during pem-cisplatin induction and had an Eastern Cooperative Oncology Group performance status (PS) of 0/1 (n=539; 57.4%) were randomized (2:1, stratified for disease stage, PS, and induction response) to maintenance pem (500 mg/m 2 on day 1 of a 21-day cycle) plus BSC (n=359) or placebo plus BSC (n=180) until disease progression. All pts received vitamin B 12 , folic acid, and dexamethasone. The primary endpoint was PFS (target: HR=0.65, two-sided alpha=0.05; 90% power with minimum of 238 events). Results: Pt characteristics were balanced between arms: median age=61 years; 58% male; 95% Caucasian; 32% PS 0; 91% stage IV; 87% adenocarcinoma; and 45% induction complete/partial response. Pem continuation maintenance resulted in a 36% reduction in the risk of progression (HR=0.64, 95% CI: 0.51-0.81; P=0.00025). The median independently reviewed PFS (472 pts, 297 events), measured from randomization, was 3.9 months (95% CI: 3.0-4.2) on the pem arm, and 2.6 months (95% CI: 2.2-2.9) on the placebo arm. The disease control rate (% pts with response/stable disease) was 71.8% on the pem arm, and 59.6% on the placebo arm (P=0.009). The drug-related serious adverse event (AE) rate was 8.9% on the pem arm, and 9.2% of pts had grade 3/4 laboratory Common Toxicity Criteria AEs. On the placebo arm, the rates were 2.8% and 0.6%, respectively. Discontinuations due to AEs were 5.3% on the pem arm, 3.3% on the placebo arm. Conclusions: PARAMOUNT met its primary endpoint and showed that pem continuation maintenance following pem-cisplatin induction is an effective and well tolerated treatment for pts with advanced nonsquamous NSCLC.