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

Paz‐Ares, Luis; Marinis, Filippo de; Dediu, Mircea; Thomas, Michael; Pujol, Jean Louis; Bidoli, Paolo; Molinier, Olivier; Sahoo, Tapan Kumar; Laack, Eckart; Reck, Martin; Corral, J.; Melemed, Symantha; John, William J.; Chouaki, N.; Zimmermann, Annamaria H.; Visseren‐Grul, Carla; Gridelli, Cesare

doi:10.1200/jco.2012.47.1102

Cited by 570 publications

(441 citation statements)

References 28 publications

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“…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).…”

Section: Resultssupporting

confidence: 70%

“…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.…”

Section: Patients and Study Designmentioning

confidence: 99%

“…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.…”

Section: Patients and Study Designmentioning

confidence: 99%

“…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.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…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].…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2014

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Highlights•Compared advanced NSCLC phase III trials: pemetrexed-cisplatin with or without pem maintenance.•4 cycles pem-cis followed by pem maintenance improves survival over 6 cycles pem-cis.•Longer exposure to pem-cis or maintenance pem increases some toxicities, but overall incidence low. Abstract ObjectivesTwo phase III trials of advanced NSCLC patients were compared to examine relative efficacy and safety of differing treatment regimens. The JMDB trial investigated first-line pemetrexed-cisplatin (pemetrexed 500 mg/m 2 plus cisplatin 75 mg/m 2 every 21 days; maximum: 6 cycles). The PARAMOUNT phase III trial compared maintenance pemetrexed versus placebo after patients with nonsquamous NSCLC completed 4 cycles of first-line pemetrexed-cisplatin without disease progression. MethodsOverall survival (OS) and progression-free survival (PFS), analyzed by Kaplan-Meier and Cox methods, and toxicity rates were compared between the PARAMOUNT arms and a selected homogeneous population from JMDB: 346 patients with disease and prior treatment characteristics matching the PARAMOUNT population. ResultsOutcomes for the PARAMOUNT placebo arm were similar to the JMDB homogeneous group (median PFS: 5.6 versus 6.2 months, p = 0.117, HR = 1.16; median OS: 14.0 versus 14.2 months, p = 0.979, HR = 1.00). The PARAMOUNT maintenance pemetrexed group had statistically superior efficacy compared with the JMDB homogeneous group (median PFS: 7.5 versus 6.2 months, p < 0.00001, HR = 0.66; median OS: 16.9 versus 14.2 months, p = 0.003, HR = 0.75). Patients who received pemetrexed maintenance (median 4 cycles, range 1-44) following 4 cycles of pemetrexed-cisplatin exhibited a higher incidence of drug-related serious adverse events compared with JMDB patients (median 6 cycles of pemetrexed-cisplatin) (10.6% versus 2.9%); grade 3/4 fatigue and renal toxicity were also higher in the pemetrexed arm of PARAMOUNT. ConclusionsThe across-trial comparison of a relevant JMDB study population with the two arms of the PARAMOUNT study supported the efficacy of the pemetrexed continuation maintenance strategy and suggested the results are not influenced by limiting the pemetrexed-cisplatin induction treatment to four cycles. Although longer exposure to pemetrexed-cisplatin or maintenance pemetrexed increased some toxicities, the overall incidence remained low, underscoring the relative safety of these treatment regimens.

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Section: Resultssupporting

confidence: 70%

Section: Patients and Study Designmentioning

confidence: 99%

Section: Patients and Study Designmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2014

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Consolidative Radiotherapy for Limited Metastatic Non–Small-Cell Lung Cancer

et al. 2018

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Cost-effectiveness and Budgetary Consequence Analysis of Durvalumab Consolidation Therapy vs No Consolidation Therapy After Chemoradiotherapy in Stage III Non–Small Cell Lung Cancer in the Context of the US Health Care System

et al. 2019

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In early 2018, durvalumab became the first immunotherapy to be approved for adjuvant treatment of patients with unresectable stage III non-small cell lung cancer (NSCLC) whose cancer has not progressed after definitive chemoradiotherapy. However, the cost-effectiveness and potential economic implications of using this high-priced therapy in this indication are unknown to date. OBJECTIVE To explore the cost-effectiveness and potential budgetary consequences of durvalumab consolidation therapy vs no consolidation therapy after chemoradiotherapy in stage III NSCLC in the context of the US health care system. DESIGN, SETTING, AND PARTICIPANTS A decision analytic microsimulation model was developed in an academic medical setting to compare the following 2 postchemoradiotherapy strategies: all patients receive no consolidation therapy until progression vs all patients receive durvalumab consolidation therapy until progression or for a maximum of 1 year. The potential budgetary consequence was calculated by applying the proportion of patients with NSCLC who were diagnosed in stage III and received chemoradiotherapy to the projected number of annual new cases for 2018 to 2022 to find total eligible patients and then multiplied by the mean difference in annual cost between the strategies over this 5-year period. Simulated conditions were matched to those of the PACIFIC phase 3 randomized clinical trial and reasonable treatment strategies for metastatic NSCLC. All simulated patients begin disease free after having received radical treatment with chemoradiotherapy and are followed up as they progress to metastatic disease first-line treatment, metastatic disease second-line treatment, end-stage progressive disease, and death. MAIN OUTCOMES AND MEASURES The main outcome of this study was the incremental cost-effectiveness ratio of durvalumab consolidation therapy vs no consolidation therapy, given as aggregate cost of treatment per quality-adjusted life-year gained.

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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

Cited by 570 publications

References 28 publications

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

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

Consolidative Radiotherapy for Limited Metastatic Non–Small-Cell Lung Cancer

Cost-effectiveness and Budgetary Consequence Analysis of Durvalumab Consolidation Therapy vs No Consolidation Therapy After Chemoradiotherapy in Stage III Non–Small Cell Lung Cancer in the Context of the US Health Care System

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