TY - JOUR
T1 - Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer
T2 - a randomised, double-blind, phase 3 study
AU - Ciuleanu, Tudor
AU - Brodowicz, Thomas
AU - Zielinski, Christoph
AU - Kim, Joo Hang
AU - Krzakowski, Maciej
AU - Laack, Eckart
AU - Wu, Yi Long
AU - Bover, Isabel
AU - Begbie, Stephen
AU - Tzekova, Valentina
AU - Cucevic, Branka
AU - Pereira, Jose Rodrigues
AU - Yang, Sung Hyun
AU - Madhavan, Jayaprakash
AU - Sugarman, Katherine P.
AU - Peterson, Patrick
AU - John, William J.
AU - Krejcy, Kurt
AU - Belani, Chandra P.
N1 - Funding Information:
The study was sponsored and funded by Eli Lilly. We thank all patients, their families, and the staff at participating centres; and Asavari Wagle and Noelle Gasco of Eli Lilly, Indianapolis, USA, for editorial support. This Article is an original report that was presented in part at the 44th American Society of Clinical Oncology Annual Meeting in Chicago, IL, USA on May 30–June 3, 2008, and at the 45th American Society of Clinical Oncology Annual Meeting in Orlando, FL, USA on May 28–June 1, 2009.
PY - 2009
Y1 - 2009
N2 - Background: Several studies have shown the efficacy, tolerability, and ease of administration of pemetrexed-an antifolate antineoplastic agent-in patients with advanced non-small-cell lung cancer. We assessed pemetrexed as maintenance therapy in patients with this disease. Methods: This randomised double-blind study was undertaken in 83 centres in 20 countries. 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy were randomly assigned (2:1 ratio) to receive pemetrexed (500 mg/m2, day 1) plus best supportive care (n=441) or placebo plus best supportive care (n=222) in 21-day cycles until disease progression. Treatment was randomised with the Simon and Pocock minimisation method. Patients and investigators were masked to treatment. All patients received vitamin B12, folic acid, and dexamethasone. The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00102804. Findings: All randomly assigned participants were analysed. Pemetrexed significantly improved progression-free survival (4·3 months [95% CI 4·1-4·7] vs 2·6 months [1·7-2·8]; hazard ratio [HR] 0·50, 95% CI 0·42-0·61, p<0·0001) and overall survival (13·4 months [11·9-15·9] vs 10·6 months [8·7-12·0]; HR 0·79, 0·65-0·95, p=0·012) compared with placebo. Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group (21 [5%] vs three [1%]). Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo (70 [16%] vs nine [4%]; p<0·0001), specifically fatigue (22 [5%] vs one [1%], p=0·001) and neutropenia (13 [3%] vs 0, p=0·006). No pemetrexed-related deaths occurred. Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy (227 [51%] vs 149 [67%]; p=0·0001). Interpretation: Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer. Funding: Eli Lilly.
AB - Background: Several studies have shown the efficacy, tolerability, and ease of administration of pemetrexed-an antifolate antineoplastic agent-in patients with advanced non-small-cell lung cancer. We assessed pemetrexed as maintenance therapy in patients with this disease. Methods: This randomised double-blind study was undertaken in 83 centres in 20 countries. 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy were randomly assigned (2:1 ratio) to receive pemetrexed (500 mg/m2, day 1) plus best supportive care (n=441) or placebo plus best supportive care (n=222) in 21-day cycles until disease progression. Treatment was randomised with the Simon and Pocock minimisation method. Patients and investigators were masked to treatment. All patients received vitamin B12, folic acid, and dexamethasone. The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00102804. Findings: All randomly assigned participants were analysed. Pemetrexed significantly improved progression-free survival (4·3 months [95% CI 4·1-4·7] vs 2·6 months [1·7-2·8]; hazard ratio [HR] 0·50, 95% CI 0·42-0·61, p<0·0001) and overall survival (13·4 months [11·9-15·9] vs 10·6 months [8·7-12·0]; HR 0·79, 0·65-0·95, p=0·012) compared with placebo. Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group (21 [5%] vs three [1%]). Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo (70 [16%] vs nine [4%]; p<0·0001), specifically fatigue (22 [5%] vs one [1%], p=0·001) and neutropenia (13 [3%] vs 0, p=0·006). No pemetrexed-related deaths occurred. Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy (227 [51%] vs 149 [67%]; p=0·0001). Interpretation: Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer. Funding: Eli Lilly.
UR - https://www.scopus.com/pages/publications/70350225538
UR - https://www.scopus.com/pages/publications/70350225538#tab=citedBy
U2 - 10.1016/S0140-6736(09)61497-5
DO - 10.1016/S0140-6736(09)61497-5
M3 - Article
C2 - 19767093
AN - SCOPUS:70350225538
SN - 0140-6736
VL - 374
SP - 1432
EP - 1440
JO - The Lancet
JF - The Lancet
IS - 9699
ER -