Long-Term and Low-Grade Safety Results of a Phase III Study (PARAMOUNT): Maintenance Pemetrexed Plus Best Supportive Care Versus Placebo Plus Best Supportive Care Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non e Small-Cell Lung Cancer

Updated long-term, low-grade (grade 1/2) safety and quality of life (QoL) results from the randomized, double-blind maintenance phase of the PARAMOUNT trial are reported. These results showed a low incidence of low-grade adverse events and uncompromised QoL, demonstrating a well-tolerated safety pro fi le for long-term pemetrexed maintenance. Introduction: In the PARAMOUNT ( “ A Phase 3, Double-Blind, Placebo-Controlled Study of Maintenance Pemetrexed plus Best Supportive Care vs. Best Supportive Care Immediately Following Induction Treatment with Pemetrexed Plus Cisplatin for Advanced Non-Squamous Non e Small-Cell Lung Cancer ” ) trial, patients with advanced nonsquamous non e small-cell lung cancer (NS-NSCLC) bene fi ted from pemetrexed maintenance therapy after induction therapy with pemetrexed and cisplatin by extending survival, delaying disease progression, and maintaining quality of life (QoL). However, low-grade 1 or 2 toxicities during long-term maintenance treatment may become burdensome and impact QoL. Materials and Methods: Patients in this double-blind study (n ¼ 539), who had completed 4 induction cycles (pemetrexed with cisplatin) without progressive disease (PD) and had an ECOG performance status of 0/1, were randomized 2:1 to pemetrexed maintenance (500 mg/m 2 , day 1) plus best supportive care (BSC) or placebo plus BSC until PD. Adverse events (by maximum Common Terminology Criteria for Adverse Events [CTCAE] grade) and QoL (EuroQol 5-dimensional [EQ-5D] scale) were assessed. Results: A median of 4 maintenance cycles was administered (range, pemetrexed 1-44; mean (cid:2) SD 7.9 (cid:2) 8.3; placebo 1-38; mean (cid:2) SD 5.0 (cid:2) 5.2), with 28% of pemetrexed and 12% of placebo patients receiving (cid:3) 10 maintenance cycles. The pemetrexed dose intensity was 94%. More patients receiving pemetrexed (12%) than placebo discontinued because of possible drug-related CTCAEs (4%; P ¼ .005). Overall, pemetrexed was associated with signi fi cantly more ( P < .05) low-grade events (grade 1/2 nausea, grade 2 anemia, edema, and neutropenia) than placebo. Overall, the incidence of low-grade fatigue, anemia, and neutropenia decreased with long-term pemetrexed exposure; however, renal events increased across treatment arms. EQ-5D analyses demonstrated no treatment-by-time interaction or overall treatment differences between the 2 arms. Conclusion: PARAMOUNT demonstrated a low incidence of low-grade toxicities with long-term pemetrexed expo-sure without compromising QoL in patients with NS-NSCLC. Clinical Lung Cancer, Vol. 15, No. 6, 418-25 ª 2014 The Authors. Published by Elsevier Inc. All rights reserved.