Chemotherapy: Open Access
Open Access
ISSN: 2167-7700
+44 1223 790975
ISSN: 2167-7700
+44 1223 790975
Abstract
Background: Maintenance therapy refers to an extended duration after frontline induction chemotherapy (CT) for patients with advanced non-small cell lung cancer (NSCLC). Several recent randomised controlled trials (RCTs) showed a survival benefit for maintenance therapy, especially for EGFR tyrosine-kinase inhibitors (TKIs), but conflicting results have been published. We performed a meta-analysis of all RCTs published either as articles or as abstracts.
Patients and Methods: A PubMed query using several keywords simultaneously (NSCLC, maintenance, RCT,survival) found 79 references. Abstracts from proceedings of ASCO and ESMO meetings were also reviewed. References were cross-checked. Outcomes were overall survival (OS) and progression free survival (PFS), both assessed by hazard ratios (HR) and their 95 % confidence interval (CI). By convention, HRs lower than 1 indicated increased survival with maintenance therapy or a lower incidence of adverse effects, compared with controls. We used a fixed effect model when heterogeneity was absent and random effect model when present. We used EasyMA software.
Results: Thirteen RCTs were included with IFCT-GFPC trial used twice since it assessed 2 maintenance
therapies in parallel, gemcitabine and erlotinib. The MA included 5251 patients (median age 61 years, 4261 stage IV, 913 stage III diseases, 2929 adenocarcinomas, 983 squamous cell carcinomas). For OS (14 sub-studies), a significant reduction in mortality favouring maintenance was observed (HR OS 0.86; CI 0.80-0.92; fixed effect model). For PFS (13 sub-studies), the overall HR was 0.65 (CI 0.58-0.73; random effect model). OS improved with continuation maintenance (6 RCTs, HR 0.89, CI 0.78-1.03) and switch maintenance (3 RCTs, HR 0.85, CI 0.75-0.98). For targeted therapies, OS also increased (5 RCTs, HR 0.85, CI 0.77-0.93). Anaemia, thrombocytopenia and neutropenia were significantly more frequent with maintenance chemotherapy, and skin rashes with EGFRTKIs.
Conclusion: Maintenance therapy with either continuation or switch chemotherapy or EGFR TKIs significantly improved OS and PFS. The benefit-to-risks balance of these 3 types of maintenance should be compared.