ABSTRACT
Pembrolizumab monotherapy has replaced chemotherapy as first-line treatment for patients with metastatic non-small-cell lung cancer with tumor programmed death-ligand 1 expression ≥ 50%. The benefit of chemotherapy combined with pembrolizumab, as compared to pembrolizumab monotherapy, remains uncertain. This systematic review and network meta-analysis aimed to compare these therapies through a network of randomized controlled trials. Endpoints evaluated were progression-free survival (PFS) and overall survival (OS) expressed as hazard ratio (HR) and restricted mean survival time (RMST) through reconstruction of individual patient data from Kaplan-Meier curves, and objective response rate and adverse events. Four trials were included. Through HR and RMST, combination therapy demonstrated longer PFS and similar OS as compared to pembrolizumab monotherapy. Combination therapy was associated with an increase in response rate and adverse events. Thus, combination therapy can be considered when rapid response or prevention of rapid progression is needed. Further evidence to directly compare these therapies is required.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung Neoplasms/pathology , Network Meta-AnalysisABSTRACT
Adjuvant chemotherapy has significantly improved outcomes following surgical resection for pancreatic adenocarcinoma; however, the optimal adjuvant strategy remains unclear. This systematic review and network meta-analysis was conducted to provide indirect comparative evidence across adjuvant chemotherapies. Electronic searches of EMBASE, MEDLINE, Cochrane and ASCO databases were conducted to identify eligible randomized controlled trials (RCT). Direct pairwise meta-analysis was conducted for disease-free survival (DFS), overall-survival (OS) and adverse events (AE). Network meta-analysis of DFS and OS was conducted to evaluate indirect comparisons. Ten publications of eleven RCT met eligibility criteria. Indirect DFS comparison demonstrated superiority of mFOLFIRINOX versus gemcitabine-capecitabine, gemcitabine-erlotinib and gemcitabine-nab-paclitaxel. S-1 demonstrated a DFS benefit versus gemcitabine-capecitabine, gemcitabine-erlotinib, gemcitabine-nab-paclitaxel. OS benefits were demonstrated for mFOLFIRINOX verus gemcitabine-erlotinib and for S-1 versus gemcitabine-based combination with erlotinib, capecitabine and nab-paclitaxel. In conclusion, mFOLFIRINOX is the preferred approach for adjuvant therapy. For mFOLFIRINOX-ineligible patients no additional benefit is seen with gemcitabine-nab-paclitaxel.