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

The present case study describes our experience in treating a young woman diagnosed with a relapsing case of diffuse large cell lymphoma, who was heavily pre-treated with chemotherapy and radiotherapy. Our only chance to improve her survival was by using high-dose chemotherapy, followed by peripheral stem cell rescue. Unfortunately, in this patient, collecting sufficient stem cells for bone marrow transplantation proved to be very difficult since she had already been heavily treated with chemotherapy and radiotherapy. Currently, granulocyte colony-stimulating factor (G-CSF) alone or G-CSF plus chemotherapy are the most commonly used treatments for stem cell mobilization. However, 5–30% of patients do not respond to these agents. Plerixafor is a new hematopoietic stem cell-mobilizing drug that antagonizes the binding of chemokine stromal cell-derived factor-1α to CXC chemokine receptor 4. It is indicated in combination with G-CSF to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma [Kessans et al.: Pharmacotherapy 2010;30:485–492; Jantunen: Expert Opin Biol Ther 2011;11:1241–1248]. Based on our findings, we consider plerixafor to be a very efficient and practical solution to mobilize and collect stem cells among all patients in such a situation, enabling us to proceed to autologous bone marrow transplantation and peripheral stem cell rescue in order to improve the patients’ overall survival.