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BMC Cancer. 2012; 12: 423.
Published online Sep 24, 2012. doi:  10.1186/1471-2407-12-423
PMCID: PMC3477017
A randomized, phase 2 study comparing pemetrexed plus best supportive care versus best supportive care as maintenance therapy after first-line treatment with pemetrexed and cisplatin for advanced, non-squamous, non-small cell lung cancer
Nabil Mubarak,corresponding author1 Rabab Gaafar,2 Samir Shehata,3 Tarek Hashem,4 Dani Abigeres,5 Hamdy A Azim,6 Gamal El-Husseiny,7 Hamed Al-Husaini,8 and Zhixin Liu9
1Medical Department, Eli Lilly and Company, Middle East and North Africa, Cairo, Egypt
2Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt
3Clinical Oncology Department, Assiut University Cancer Centre, Assiut, Egypt
4Clinical Oncology Department, Menoufia University Cancer Centre, Shibin El-Kom, Egypt
5Cancer Center Department, Middle East Institute of Health, Beirut, Lebanon
6Clinical Oncology Department, Kasr El-Einy Cancer Institute, Cairo University, Cairo, Egypt
7Clinical Oncology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
8Oncology Department, King Faisal Specialist Centre and Research Centre, Riyad, Saudi Arabia
9Statistical Sciences Department, Eli Lilly Australia, Sydney, Australia
corresponding authorCorresponding author.
Nabil Mubarak: MUBARAK_NABIL/at/LILLY.COM; Rabab Gaafar: rababgaafar/at/link.net; Samir Shehata: samir_eid/at/hotmail.com; Tarek Hashem: thashem1/at/hotmail.com; Dani Abigeres: abgerges/at/idm.net.lb; Hamdy A Azim: azimonc/at/cairocure.com; Gamal El-Husseiny: gamal99/at/hotmail.com; Hamed Al-Husaini: hhussaini/at/gmail.com; Zhixin Liu: LIU_ZHIXIN/at/LILLY.COM
Received January 11, 2012; Accepted August 21, 2012.
Abstract
Background
Maintenance therapy for non-small cell lung cancer (NSCLC) aims to extend disease control after first-line chemotherapy with active and well-tolerated agents. The utility of continuation maintenance therapy requires further research.
Methods
This multicenter, randomized, phase 2 study compared continuation maintenance therapy with pemetrexed (500 mg/m2 every 21 days) and best supportive care (BSC) versus BSC alone in patients with advanced, non-squamous NSCLC who had not progressed after 4 cycles of induction chemotherapy with pemetrexed (500 mg/m2) and cisplatin (75 mg/m2). The primary endpoint was progression-free survival (PFS) from randomization, was analyzed using a Cox model, stratified for the tumor response at the end of induction therapy, at a one-sided alpha of 0.2. Secondary endpoints: response and disease control rates, overall survival (OS), one year survival rates, and treatment-emergent adverse events (TEAEs).
Results
A total of 106 patients commenced induction therapy, of whom 55 patients were randomized to maintenance pemetrexed/BSC (n = 28) or BSC (n = 27). Although the median PFS time for maintenance phase for both arms was 3.2 months, the one-sided p-value for the PFS HR comparison was less than the prespecified limit of 0.2 (HR = 0.76, two-sided 95% confidence interval [CI]: 0.42 to 1.37; one-sided p-value = 0.1815), indicating that PFS was sufficiently long in the pemetrexed/BSC arm to warrant further investigation. Similar PFS results were observed for the overall study period (induction plus maintenance) and when the PFS analysis was adjusted for sex, baseline disease stage, and the ECOG PS prior to randomization. The median OS for the maintenance phase was 12.2 months (95%CI: 5.6 to 20.6) for the pemetrexed/BSC arm and 11.8 months (95% CI: 6.3 to 25.6) for BSC arm. The one-year survival probabilities were similar for both arms for the maintenance phase and the overall study period. Both the induction and continuation maintenance therapies were generally well-tolerated, and similar proportion of patients in each arm experienced at least 1 grade 3/4 TEAE (pemetrexed/BSC, 17.9%; BSC, 18.5%).
Conclusions
Continuation pemetrexed maintenance therapy resulted in promising PFS with an acceptable safety profile in a Middle Eastern population with advanced non-squamous NSCLC and is worthy of further investigation.
Trial registration
NCT00606021
Keywords: Non-squamous, Non-small cell lung cancer, Pemetrexed, Cisplatin, Induction, Maintenance
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