PARAMOUNT: Descriptive Subgroup Analyses of Final Overall Survival for the Phase III Study of Maintenance Pemetrexed versus Placebo Following Induction Treatment with Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non–Small-Cell Lung Cancer

PurposeCisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non–small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting.Patients and MethodsThis noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2on day 1 and gemcitabine 1,250 mg/m2on days 1 and 8 (n = 863) or cisplatin 75 mg/m2and pemetrexed 500 mg/m2on day 1 (n = 862) every 3 weeks for up to six cycles.ResultsOverall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P ≤ .001); febrile neutropenia (P = .002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4 nausea (P = .004) was more common.ConclusionIn advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

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PARAMOUNT: Phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) versus placebo plus BSC immediately following induction treatment with pem plus cisplatin for advanced nonsquamous non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.cra7510 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. CRA7510-CRA7510 ◽

Cited By ~ 1

Author(s):

L. G. Paz-Ares ◽

F. De Marinis ◽

M. Dediu ◽

M. Thomas ◽

J. Pujol ◽

...

Keyword(s):

Lung Cancer ◽

Supportive Care ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Best Supportive Care ◽

Small Cell ◽

Phase Iii ◽

Induction Treatment ◽

Small Cell Lung ◽

Phase Iii Study

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Phase III Study of Pemetrexed Plus Carboplatin Compared With Etoposide Plus Carboplatin in Chemotherapy-Naive Patients With Extensive-Stage Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.23.1548 ◽

2009 ◽

Vol 27 (28) ◽

pp. 4787-4792 ◽

Cited By ~ 108

Author(s):

Mark A. Socinski ◽

Egbert F. Smit ◽

Paul Lorigan ◽

Kartik Konduri ◽

Martin Reck ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Phase Iii ◽

Small Cell Lung ◽

Phase Iii Study ◽

Extensive Stage ◽

Grade 3

Purpose Following a phase II trial in which pemetrexed-platinum demonstrated similar activity to that of historical etoposide-platinum controls, a phase III study was conducted to compare pemetrexed-carboplatin with etoposide-carboplatin for the treatment of extensive-stage small-cell lung cancer (ES-SCLC). Patients and Methods Chemotherapy-naive patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status of zero to 2 were randomly assigned to receive pemetrexed-carboplatin (pemetrexed 500 mg/m2 on day 1; carboplatin at area under the serum concentration-time curve [AUC] 5 on day 1) or etoposide-carboplatin (etoposide 100 mg/m2 on days 1 through 3; carboplatin AUC 5 on day 1) every 3 weeks for up to six cycles. The primary objective of the study was noninferiority of pemetrexed-carboplatin overall survival with a 15% margin. Results Accrual was terminated with 908 of 1,820 patients enrolled after results of a planned interim analysis. In the final analysis, pemetrexed-carboplatin was inferior to etoposide-carboplatin for overall survival (median, 8.1 v 10.6 months; hazard ratio [HR],1.56; 95% CI, 1.27 to 1.92; log-rank P < .01) and progression-free survival (median, 3.8 v 5.4 months; HR, 1.85; 95% CI, 1.58 to 2.17; log-rank P < .01). Objective response rates were also significantly lower for pemetrexed-carboplatin (31% v 52%; P < .001). Pemetrexed-carboplatin had lower grade 3 to 4 neutropenia, febrile neutropenia, and leukopenia than etoposide-carboplatin; grade 3 to 4 thrombocytopenia was comparable between arms and anemia was higher in the pemetrexed-carboplatin arm. Conclusion Pemetrexed-carboplatin is inferior for the treatment of ES-SCLC. Planned translational research and pharmacogenomic analyses of tumor and blood samples may help explain the study results and provide insight into new treatment strategies.

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Randomized Phase III Study of Gemcitabine and Vinorelbine Versus Gemcitabine, Vinorelbine, and Cisplatin in the Treatment of Advanced Non-Small-Cell Lung Cancer: From the German and Swiss Lung Cancer Study Group

Journal of Clinical Oncology ◽

10.1200/jco.2004.10.576 ◽

2004 ◽

Vol 22 (12) ◽

pp. 2348-2356 ◽

Cited By ~ 73

Author(s):

E. Laack ◽

N. Dickgreber ◽

T. Müller ◽

A. Knuth ◽

J. Benk ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Phase Iii ◽

Small Cell Lung ◽

First Line ◽

Significant Difference ◽

Phase Iii Study

Purpose To evaluate whether cisplatin-based chemotherapy (gemcitabine, vinorelbine, and cisplatin [GVP]) prolongs overall survival in comparison to cisplatin-free chemotherapy (gemcitabine and vinorelbine [GV]) as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods Between September 1999 and June 2001, 300 patients with NSCLC stage IIIB with malignant pleural effusion or stage IV disease were randomly assigned to receive GV (gemcitabine 1000 mg/m2 + vinorelbine 25 mg/m2 on days 1 and 8 every 3 weeks) or GVP (gemcitabine 1000 mg/m2 + vinorelbine 25 mg/m2 on days 1 and 8 + cisplatin 75 mg/m2 on day 2 every 3 weeks). Primary end point of the study was overall survival. Results Two hundred eighty-seven patients (GV, 143 patients; GVP, 144 patients) were eligible for analysis. At the time of analysis, April 15, 2002, 209 patients (GV, 103 patients; GVP, 106 patients) of 287 patients had died (73%). No statistically significant difference was observed for overall survival (P = .73; median survival, 35.9 versus 32.4 weeks; 1-year survival rate, 33.6% versus 27.5%) as well as for event-free survival (P = .35; median time-to-event, 19.3 versus 22.3 weeks) between GV and GVP. Two hundred fourteen patients were assessable for best response. The overall response rates were 13.0% for GV versus 28.3% for GVP (P = .004; complete responders, 0% versus 3.8%; partial responders, 13.0% versus 24.5%). Hematologic and nonhematologic toxicity was significantly lower in the GV treatment arm compared with GVP. No statistically significant difference in quality of life was observed. Conclusion In this phase III study, the cisplatin-based GVP regimen showed no survival benefit as first-line chemotherapy in advanced NSCLC when compared with the cisplatin-free GV regimen, which was substantially better tolerated.

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