Systematic review and network meta-analyses of third-line treatments for metastatic colorectal cancer

Abstract

Background Limited treatment options are available in chemotherapy-refractory metastatic colorectal cancer (mCRC). 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 (HRs) for OS using Markov chain Monte Carlo (MCMC) techniques. Results Seven studies were identified in the SLR: two double-blind randomized-controlled trials (RCT) for each drug, one open-label RCT, and two non-randomized comparative studies for SIRT. Patient selection criteria differed between studies, with SIRT studies including patients with liver-dominant colorectal metastases. Nausea and vomiting were more frequent with TAS-102 than regorafenib or SIRT; diarrhea was more common with TAS-102 and regorafenib than 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. Conclusions Regorafenib, TAS-102 and SIRT using Y-90 resin microspheres are more effective than BSC in third-line treatment of mCRC; however, study heterogeneity made comparisons between active treatments challenging. SIRT is a viable treatment for third-line mCRC and its favorable AE profile should be considered in the therapeutic decision-making process.

A Positive Feedback Loop of lncRNA MIR31HG-miR-361-3p -YY1 Accelerates Colorectal Cancer Progression Through Modulating Proliferation, Angiogenesis, and Glycolysis

“…Colorectal cancer (CRC) is among the most frequent and lethal tumors in the world, and its occurrence and development are closely related to genetic factors, dietary habits, and inflammation (1). Besides, the mortality and morbidity of CRC are high due to the inconspicuous early symptoms and high metastatic rate (2,3). Traditional therapies including surgery, chemotherapy, and radiotherapy have improved the survival of CRC patients.…”

Low-Dose Apatinib Combined With S-1 in Refractory Metastatic Colorectal Cancer: A Phase 2, Multicenter, Single-Arm, Prospective Study

“…Numerous patients with mCRC having disease progression after receiving all standard therapies still exhibit an adequate ECOG PS to tolerate further treatment. Recent drugs regorafenib, fruquintinib, and TAS-102 have superior efficacy compared with the placebo, therefore they would be suitable for third-line therapy in mCRC ( 11 , 27 ). Unfortunately, the survival effect of the third-line CRC treatment in phase 3 trials is modest.…”

Preference criteria for regorafenib in treating refractory metastatic colorectal cancer are the small tumor burden, slow growth and poor/scanty spread

“…Unfortunately, approximately 40% of patients with stage I–III finally progress to mCRC 5 . Despite the advancement of biochemotherapy for the treatment of mCRC, the median overall survival (OS) remains at 30–36 months 6 – 10 . Before the availability of new agents, the more precise strategy in selecting the right biochemotherapy for the right patients remains the cornerstone for mCRC treatment.…”

“…Treatment of mCRC may consist of chemotherapy, precision cancer medicines, and immunotherapy or some combination that is often determined by genomic testing of the cancer 2 , 6 , 9 – 17 . Some patients might be only treated with precision cancer agents or immunotherapy 16 , 17 and might avoid chemotherapy at initial treatment.…”

“…Sadly, the PR rate of both regorafenib and TAS-102 is approximately 1%–3%, comprising 60% of patients who did not respond to these agents. To date, several studies 6 , 25 – 28 , 30 – 33 try to prove the sequence of regorafenib and TAS-102 for the treatment of refractory mCRC, and majority of them point out that their sequences did affect the OS 33 – 36 . However, a key difference was observed between regorafenib and TAS-102.…”