PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non–Small-Cell Lung Cancer

• Published in: Journal of clinical oncology Vol. 31; no. 23; pp. 2895 - 2902
• Main Authors: PAZ-ARES, Luis G, DE MARINIS, Filippo, CORRAL, Jesús, MELEMED, Symantha, JOHN, William, CHOUAKI, Nadia, ZIMMERMANN, Annamaria H, VISSEREN-GRUL, Carla, GRIDELLI, Cesare, DEDIU, Mircea, THOMAS, Michael, PUJOL, Jean-Louis, BIDOLI, Paolo, MOLINIER, Olivier, TARINI PRASAD SAHOO, LAACK, Eckart, RECK, Martin
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10-08-2013
• Subjects: Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Cisplatin - administration & dosage; Cisplatin - adverse effects; Disease-Free Survival; Double-Blind Method; Female; Glutamates - administration & dosage; Glutamates - adverse effects; Glutamates - therapeutic use; Guanine - administration & dosage; Guanine - adverse effects; Guanine - analogs & derivatives; Guanine - therapeutic use; Humans; Induction Chemotherapy; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Pemetrexed; Pneumology; Remission Induction; Survival Analysis; Treatment Outcome; Tumors; Tumors of the respiratory system and mediastinum; Antineoplastic agent; Phase III trial; Lung disease; Respiratory disease; Lung cancer; Malignant tumor; non-small cell lung carcinoma; Pemetrexed; Survival; Induction treatment; Cisplatin; Antifolate; Alkylating agent; Cancerology; Placebo; Bronchus disease; Advanced stage; Comparative study; Cancer; Platinum II Complexes
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2012.47.1102

In the phase III PARAMOUNT trial, pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.49 to 0.79; P < .001). Here we report final overall survival (OS) and updated safety data.
In all, 939 patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) received four cycles of pemetrexed-cisplatin induction therapy; then, 539 patients with no disease progression and Eastern Cooperative Oncology Group performance status 0 or 1 were randomly assigned (2:1) to maintenance pemetrexed (500 mg/m(2) on day 1 of 21-day cycles; n = 359) or placebo (n = 180). Log-rank test compared OS between arms as measured from random assignment (α = .0498).
The mean number of maintenance cycles was 7.9 (range, one to 44) for pemetrexed and 5.0 (range, one to 38) for placebo. After 397 deaths (pemetrexed, 71%; placebo, 78%) and a median follow-up of 24.3 months for alive patients (95% CI, 23.2 to 25.1 months), pemetrexed therapy resulted in a statistically significant 22% reduction in the risk of death (HR, 0.78; 95% CI, 0.64 to 0.96; P = .0195; median OS: pemetrexed, 13.9 months; placebo, 11.0 months). Survival on pemetrexed was consistently improved for all patient subgroups, including induction response: complete/partial responders (n = 234) OS HR, 0.81; 95% CI, 0.59 to 1.11 and stable disease (n = 285) OS HR, 0.76; 95% CI, 0.57 to 1.01). Postdiscontinuation therapy use was similar: pemetrexed, 64%; placebo, 72%. No new safety findings emerged. Drug-related grade 3 to 4 anemia, fatigue, and neutropenia were significantly higher in pemetrexed-treated patients.
Pemetrexed continuation maintenance therapy is well-tolerated and offers superior OS compared with placebo, further demonstrating that it is an efficacious treatment strategy for patients with advanced nonsquamous NSCLC and good performance status who did not progress during pemetrexed-cisplatin induction therapy.