OBJECTIVES

Limited treatment options are available in metastatic colorectal cancer (mCRC) that is refractory to chemotherapy. The objective was to conduct a systematic literature review (SLR) and exploratory network meta-analysis (NMA) to compare the tolerability and effectiveness of SIRT with Y-90 resin microspheres, regorafenib, TAS-102 (trifluridine/tipiracil) and best supportive care (BSC) as third-line treatment in patients with mCRC.

METHODS

An SLR was conducted to identify studies comparing two or more of the treatments and reporting overall survival (OS), progression-free survival, tumor response or adverse event (AE) incidence. An exploratory NMA was conducted to compare hazard ratios (HR) for OS using Markov chain Monte Carlo (MCMC) techniques.

RESULTS

Literature searches retrieved 1,334 unique studies. Title and abstract screening resulted in 40 studies eligible for full-text screening, of which 7 were ultimately included: two double-blind randomized controlled trials (RCT) for each drug, one open-label RCT and two non-randomized comparative studies for SIRT. There were differences across studies in terms of selection criteria, with studies of SIRT including patients with liver-dominant colorectal metastases, and in terms of control interventions. Diarrhea was more frequently reported as an AE with TAS-102 and regorafenib than with SIRT; nausea and vomiting were more frequent with TAS-102 than with regorafenib and SIRT. The exploratory NMA suggested that all active treatments improved OS, with HRs of 0.48 (95% CrI 0.30-0.78) for SIRT with Y-90 resin microspheres, 0.63 (0.38-1.03) for TAS-102, and 0.67 (0.40-1.08) for regorafenib each compared to BSC, in the random effects meta-analyses.

CONCLUSIONS

Regorafenib, TAS-102 and SIRT using Y-90 resin microspheres are more effective than BSC in third-line mCRC, however comparisons between active treatments are uncertain because of heterogeneity between the studies. SIRT can be considered an option in this setting and its favorable AE profile is relevant in the therapeutic decision-making process.