Pemetrexed maintenance therapy prolongs survival in nonsquamous NSCLC
medwireNews: Pemetrexed maintenance therapy offers a survival benefit over placebo and is well tolerated in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC), final results of the PARAMOUNT trial show.
In this phase 3 trial, patients with a good performance status who did not progress after induction pemetrexed–cisplatin therapy gained a further advantage in terms of both overall survival and progression-free survival if they were given pemetrexed as maintenance therapy.
“The results of the PARAMOUNT study provide evidence to direct those choices by providing new data on the benefits/risks of maintenance pemetrexed, supporting the use of continuation maintenance pemetrexed for patients with advanced nonsquamous NSCLC,” say Luis Paz-Ares (University Hospital Virgen del Rocío, Seville, Spain) and co-authors in the Journal of Clinical Oncology.
PARAMOUNT included 939 patients with advanced nonsquamous NSCLC from 83 primarily European sites. In the induction phase, all patients received four cycles of pemetrexed and cisplatin on day one of a 21-day cycle. Of the 637 patients who completed this phase, 539 were randomly assigned to maintenance therapy with either pemetrexed or placebo, starting on average 3 days after the end of induction.
The median duration of follow up was 12.5 months and the mean number of maintenance cycles was 7.9 for pemetrexed and 5.0 for placebo. Therapy was discontinued for possible treatment-related adverse events in 12.0% and 4.4% of pemetrexed- and placebo-treated patients, respectively.
Efficacy analysis revealed that pemetrexed maintenance therapy was associated with significantly longer overall survival (median 13.9 vs 11.0 months) and a 22% reduced risk for death.
“The overall survival benefit is particularly evident several months from random assignment and improves with time until approximately 12 months,” remark Paz-Ares et al.
The findings also confirmed a previously reported 40% reduction in the risk for progression or death among patients in the maintenance group.
Subgroup analyses suggested that the treatment benefit was consistent across all subgroups. Finally, an updated safety analysis found that patients receiving pemetrexed had a significantly greater incidence of grade 3/4 anemia, neutropenia, and fatigue than placebo-treated patients; however, fewer than 7% of patients were affected.
The researchers note that PARAMOUNT is the second phase 3 trial to show that pemetrexed maintenance therapy offers a survival benefit in NSCLC and say the next question to be addressed is whether pemetrexed can be re-initiated in patients who have had a break following induction therapy.
They conclude: “Our understanding of optimal use of maintenance therapy will be furthered when several ongoing clinical trials are completed over the next few years.
“Then and now, the decision to use maintenance therapy should be based on an individualized approach that includes patient-specific factors and wishes.”
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013
By Joanna Lyford, Senior medwireNews Reporter