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Open Access Research article

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 Mubarak1*, Rabab Gaafar2, Samir Shehata3, Tarek Hashem4, Dani Abigeres5, Hamdy A Azim6, Gamal El-Husseiny7, Hamed Al-Husaini8 and Zhixin Liu9

Author affiliations

1 Medical Department, Eli Lilly and Company, Middle East and North Africa, Cairo, Egypt

2 Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt

3 Clinical Oncology Department, Assiut University Cancer Centre, Assiut, Egypt

4 Clinical Oncology Department, Menoufia University Cancer Centre, Shibin El-Kom, Egypt

5 Cancer Center Department, Middle East Institute of Health, Beirut, Lebanon

6 Clinical Oncology Department, Kasr El-Einy Cancer Institute, Cairo University, Cairo, Egypt

7 Clinical Oncology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt

8 Oncology Department, King Faisal Specialist Centre and Research Centre, Riyad, Saudi Arabia

9 Statistical Sciences Department, Eli Lilly Australia, Sydney, Australia

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Citation and License

BMC Cancer 2012, 12:423  doi:10.1186/1471-2407-12-423

Published: 24 September 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