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

Abstract

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.

Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer following pemetrexed plus cisplatin induction treatment: A cross-trial comparison of two phase III trials

“…There is no statistical difference between the median OS or PFS of the two groups (PFS unadjusted HR = 1.16, 95% CI = 0.96-1.39, p = 0.117; OS unadjusted HR = 1.00, 95% CI = 0.81-1.24, p = 0.979). In contrast, the PARAMOUNT pemetrexed continuation maintenance group is not only statistically superior to the PARAMOUNT placebo group (as previously reported) [8] and [9], but also to the JMDB group, with an unadjusted HR for PFS of 0.66 (95% CI 0.56-0.77), p-value <0.00001, and for OS of 0.75 (95% CI 0.63-0.91), p-value = 0.003. Patients receiving pemetrexed continuation maintenance therapy after 4 cycles of first-line pemetrexed-cisplatin displayed significantly improved PFS and OS over those patients who received only first-line pemetrexedcisplatin (median 6 cycles).…”

“…Detailed descriptions of both trials have been previously published [5], [8] and [9]. In brief, the PARAMOUNT study enrolled 939 chemotherapy-naïve patients primarily from European centers with advanced (stage IIIB or IV) nonsquamous NSCLC to receive four 21-day cycles of pemetrexed (500 mg/m 2 ) and cisplatin (75 mg/m 2 ) induction therapy.…”

“…539 patients who completed four cycles of induction therapy with documented radiographic evidence of partial (PR) or complete (CR) tumor response or SD, and who had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, were then randomly assigned (2:1 ratio) to receive maintenance therapy with pemetrexed (500 mg/m 2 ) (n = 359) or placebo (9% sodium chloride) (n = 180). All randomized patients were included in the previously reported efficacy and safety analysis populations [8] and [9] and are included in the analyses described here.…”

“…All analyses were run for the two randomized arms of PARAMOUNT in comparison to the selected homogeneous population from JMDB. Detailed descriptions of the primary statistical analyses of both studies have been previously published [5], [8] and [9]. The following analyses were carried out for the three treatment groups: Kaplan-Meier estimates (including medians) for PFS and OS; Cox hazard ratio estimates [with p-values and 95% confidence intervals (CIs)] for PFS and OS.…”

“…More recently, the PARAMOUNT study examined pemetrexed continuation maintenance therapy following four cycles of pemetrexed-cisplatin as induction treatment and found significantly improved PFS and OS when administered to non-progressing patients with advanced, nonsquamous NSCLC [8] and [9]. Current guidelines recommend maintenance single-agent pemetrexed for patients with stable disease (SD) or tumor response after four cycles of platinum-containing induction therapy [2], [3] and [4].…”