Luís Paz-Ares1, Filippo de Marinis1, Mircea Dediu1, Michael Thomas1, Jean-Louis Pujol1, Paolo Bidoli1, Olivier Molinier1, Tarini Prasad Sahoo1, Eckart Laack1, Martin Reck1, J. Corral1, Symantha Melemed1, William J. John1, Nadia Chouaki1, Annamaria H. Zimmermann1, Carla Visseren‐Grul1, Cesare Gridelli1
1Luis Paz-Ares and Jesús Corral, University Hospital Virgen del Rocío, Seville, Spain; Filippo de Marinis, San Camillo-Forlanini Hospital, Rome; Paolo Bidoli, S. Gerardo Hospital, Monza; Cesare Gridelli, San Giuseppe Moscati Hospital, Avellino, Italy; Mircea Dediu, Institute of Oncology Bucharest, Bucharest, Romania; Michael Thomas, University of Heidelberg, Heidelberg; Eckart Laack, University Medical Center Hamburg-Eppendorf, Hamburg; Martin Reck, Hospital Grosshansdorf, Grosshansdorf, Germany; Jean...
Tóm tắt
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/m2 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.
