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
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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. / Paz-Ares, Luis G; de Marinis, Filippo; Dediu, Mircea; Thomas, Michael; Pujol, Jean-Louis; Bidoli, Paolo; Molinier, Olivier; Sahoo, Tarini Prasad; Laack, Heinz-Eckart; Reck, Martin; Corral, Jesús; Melemed, Symantha; John, William; Chouaki, Nadia; Zimmermann, Annamaria H; Visseren-Grul, Carla; Gridelli, Cesare.
In: J CLIN ONCOL, Vol. 31, No. 23, 10.08.2013, p. 2895-902.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - 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
AU - Paz-Ares, Luis G
AU - de Marinis, Filippo
AU - Dediu, Mircea
AU - Thomas, Michael
AU - Pujol, Jean-Louis
AU - Bidoli, Paolo
AU - Molinier, Olivier
AU - Sahoo, Tarini Prasad
AU - Laack, Heinz-Eckart
AU - Reck, Martin
AU - Corral, Jesús
AU - Melemed, Symantha
AU - John, William
AU - Chouaki, Nadia
AU - Zimmermann, Annamaria H
AU - Visseren-Grul, Carla
AU - Gridelli, Cesare
PY - 2013/8/10
Y1 - 2013/8/10
N2 - PURPOSE: In the phase III PARAMOUNT trial, pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.49 to 0.79; P < .001). Here we report final overall survival (OS) and updated safety data.PATIENTS AND METHODS: In all, 939 patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) received four cycles of pemetrexed-cisplatin induction therapy; then, 539 patients with no disease progression and Eastern Cooperative Oncology Group performance status 0 or 1 were randomly assigned (2:1) to maintenance pemetrexed (500 mg/m(2) on day 1 of 21-day cycles; n = 359) or placebo (n = 180). Log-rank test compared OS between arms as measured from random assignment (α = .0498).RESULTS: The mean number of maintenance cycles was 7.9 (range, one to 44) for pemetrexed and 5.0 (range, one to 38) for placebo. After 397 deaths (pemetrexed, 71%; placebo, 78%) and a median follow-up of 24.3 months for alive patients (95% CI, 23.2 to 25.1 months), pemetrexed therapy resulted in a statistically significant 22% reduction in the risk of death (HR, 0.78; 95% CI, 0.64 to 0.96; P = .0195; median OS: pemetrexed, 13.9 months; placebo, 11.0 months). Survival on pemetrexed was consistently improved for all patient subgroups, including induction response: complete/partial responders (n = 234) OS HR, 0.81; 95% CI, 0.59 to 1.11 and stable disease (n = 285) OS HR, 0.76; 95% CI, 0.57 to 1.01). Postdiscontinuation therapy use was similar: pemetrexed, 64%; placebo, 72%. No new safety findings emerged. Drug-related grade 3 to 4 anemia, fatigue, and neutropenia were significantly higher in pemetrexed-treated patients.CONCLUSION: 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.
AB - PURPOSE: In the phase III PARAMOUNT trial, pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.49 to 0.79; P < .001). Here we report final overall survival (OS) and updated safety data.PATIENTS AND METHODS: In all, 939 patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) received four cycles of pemetrexed-cisplatin induction therapy; then, 539 patients with no disease progression and Eastern Cooperative Oncology Group performance status 0 or 1 were randomly assigned (2:1) to maintenance pemetrexed (500 mg/m(2) on day 1 of 21-day cycles; n = 359) or placebo (n = 180). Log-rank test compared OS between arms as measured from random assignment (α = .0498).RESULTS: The mean number of maintenance cycles was 7.9 (range, one to 44) for pemetrexed and 5.0 (range, one to 38) for placebo. After 397 deaths (pemetrexed, 71%; placebo, 78%) and a median follow-up of 24.3 months for alive patients (95% CI, 23.2 to 25.1 months), pemetrexed therapy resulted in a statistically significant 22% reduction in the risk of death (HR, 0.78; 95% CI, 0.64 to 0.96; P = .0195; median OS: pemetrexed, 13.9 months; placebo, 11.0 months). Survival on pemetrexed was consistently improved for all patient subgroups, including induction response: complete/partial responders (n = 234) OS HR, 0.81; 95% CI, 0.59 to 1.11 and stable disease (n = 285) OS HR, 0.76; 95% CI, 0.57 to 1.01). Postdiscontinuation therapy use was similar: pemetrexed, 64%; placebo, 72%. No new safety findings emerged. Drug-related grade 3 to 4 anemia, fatigue, and neutropenia were significantly higher in pemetrexed-treated patients.CONCLUSION: 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.
KW - Antimetabolites, Antineoplastic
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Carcinoma, Non-Small-Cell Lung
KW - Cisplatin
KW - Disease-Free Survival
KW - Double-Blind Method
KW - Female
KW - Glutamates
KW - Guanine
KW - Humans
KW - Induction Chemotherapy
KW - Lung Neoplasms
KW - Male
KW - Middle Aged
KW - Remission Induction
KW - Survival Analysis
KW - Treatment Outcome
U2 - 10.1200/JCO.2012.47.1102
DO - 10.1200/JCO.2012.47.1102
M3 - SCORING: Journal article
C2 - 23835707
VL - 31
SP - 2895
EP - 2902
JO - J CLIN ONCOL
JF - J CLIN ONCOL
SN - 0732-183X
IS - 23
ER -