PARAMOUNT: Final overall survival (OS) results of the phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) versus placebo (plb) plus BSC immediately following induction treatment with pem plus cisplatin (cis) for advanced nonsquamous (NS) non-small cell lung cancer (NSCLC).

Abstract

LBA7507 Background: The PARAMOUNT trial showed that pem continuation maintenance therapy significantly reduced the risk of disease progression over plb (HR=0.62; 95% CI: 0.49-0.79; p <0.0001) in patients (pts) with advanced NS NSCLC who had not progressed during pem-cis induction. Here we present the final OS data. Methods: In a double-blind, plb-controlled study, alpha-controlled for OS, 939 pts received induction (4 cycles of pem 500 mg/m2 and cis 75 mg/m2 on d1 of 21d cycles), and 539 pts who had not progressed and had an ECOG performance status (PS) of 0/1 were randomized (2:1) to maintenance pem (500 mg/m2, on day 1 of 21-day cycles) plus BSC or plb plus BSC until disease progression. All received B12, folic acid, and dexamethasone. After 397 deaths, a log-rank test compared OS between arms using anominal α level of 0.0498. Results: Pt characteristics were balanced between arms: median age 61 years; 58% men; 32% PS 0; 95% Caucasian; 86% adenocarcinoma; 45% complete/partial response (CR/PR) to induction. Pem resulted in a statistically significant 22% reduction in risk of death (HR=0.78). The HR was the same when measured from the beginning of induction. Survival improvement was similar for pts with an induction outcome of CR/PR versus stable disease. Conclusions: Pem continuation maintenance therapy offers superior OS compared with plb. These final results confirm that pem-cis induction followed by continuation pem further benefits pts compared with induction therapy alone, offering a change in the treatment paradigm for advanced NS NSCLC. [Table: see text]

Pemetrexed as a Component of First-, Second- and Third-line Chemotherapy in Treating Patients with Metastatic Lung Adenocarcinoma

“…The hazard ratio for PFS is in the range of 0.6 to 0.7 in most of the trials for both strategies. OS is only significantly improved in the SATURN (Cappuzzo et al, 2010) andJMEN (Ciuleanu et al, 2009) switchmaintenance trials, and in the PARAMOUNT trial (Paz- Ares et al, 2012) with the continuation strategy. These were the only three trials with a reasonable size (539 to 889 patients) to enable adequately powered comparisons.…”

“…The PARAMOUNT trial revealed that pemetrexed maintenance therapy could improve efficacy over placebo following four courses of cisplatin/pemetrexed (Paz- Ares et al, 2011). The primary objective of this study, PFS, was improved in the pemetrexed maintenance arm compared with placebo (4.1 vs. 2.8 months, HR 0.62), and OS was also significantly improved (13.9 vs. 11 months, HR 0.78) (Paz- Ares et al, 2012).…”

Thoracic Oncology HERMES syllabus: setting the basis for thoracic oncology training in Europe: Table 1–

“…In the last decades, the interest in lung cancer and pleural mesothelioma has rapidly increased. Lung cancer is currently the deadliest cancer [5], but there have been considerable advances in the diagnosis and treatment of this disease that has led to an improvement of median survival in advanced-stage lung cancers from 7-8 months in 2000 [6] to 15 months in 2010 [7]. The incidence of mesothelioma is still increasing worldwide [8].…”

Overall Survival Should Be the Primary Endpoint in Clinical Trials for Advanced Non-Small-Cell Lung Cancer

“…The significant pfs that was observed did not translate into an os benefit (os being the primary endpoint of the trial), nor was qol improved. More recent practice-changing clinical trials supporting maintenance systemic treatments after a platinum doublet have used pfs as the primary endpoint (Table iii) [46][47][48][49] . Pemetrexed has been studied in the jmen and paramount trials, and erlotinib in the saturn trial, as maintenance after platinum doublet, and both a pfs and an os benefit have been reported, suggesting a correlation [46][47][48][49] .…”

“…More recent practice-changing clinical trials supporting maintenance systemic treatments after a platinum doublet have used pfs as the primary endpoint (Table iii) [46][47][48][49] . Pemetrexed has been studied in the jmen and paramount trials, and erlotinib in the saturn trial, as maintenance after platinum doublet, and both a pfs and an os benefit have been reported, suggesting a correlation [46][47][48][49] . Docetaxel, pemetrexed, and erlotinib are all agents that have shown a pfs and os benefit in the second-line setting, and thus it is not surprising that, compared with best supportive care, giving active drug earlier delays progression as has been reported 18,[38][39][40] .…”