• Jean-Louis Pujol, Luis Paz-Ares, Filippo de Marinis, Mircea Dediu, Michael Thomas, Paolo Bidoli, Jesus Corral, Belen San Antonio, Nadia Chouaki, William John, Annamaria Zimmermann, Carla Visseren-Grul, and Cesare Gridelli.
• Montpellier University Hospital, Montpellier, France. Electronic address: jl-pujol@chu-montpellier.fr.
• Clin Lung Cancer. 2014 Nov 1;15(6):418-25.

IntroductionIn 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-Small-Cell Lung Cancer") trial, patients with advanced nonsquamous non-small-cell lung cancer (NS-NSCLC) benefited 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 MethodsPatients in this double-blind study (n = 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.ResultsA median of 4 maintenance cycles was administered (range, pemetrexed 1-44; mean ± SD 7.9 ± 8.3; placebo 1-38; mean ± SD 5.0 ± 5.2), with 28% of pemetrexed and 12% of placebo patients receiving ≥ 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 = .005). Overall, pemetrexed was associated with significantly 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.ConclusionPARAMOUNT demonstrated a low incidence of low-grade toxicities with long-term pemetrexed exposure without compromising QoL in patients with NS-NSCLC.Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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