Efficacy and Safety of Systemic Treatments Among Colorectal Cancer Patients: A Network Meta-Analysis of Randomized Controlled Trials

Abstract

BackgroundSystemic treatments, namely, either monotherapy or combination therapy, are commonly administered to patients with advanced or metastatic colorectal cancer (CRC). This study aimed to provide the complete efficacy and safety profiles and ranking of systemic therapies for the treatment of unresectable advanced or metastatic CRC.MethodsWe searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception until June 30, 2021, and also the bibliographies of relevant studies. Randomized controlled trials comparing two or more treatments, namely, at least capecitabine, 5-fluorouracil, leucovorin, irinotecan, bevacizumab, cetuximab, oxaliplatin, or panitumumab were investigated. A network meta-analysis using the Bayesian approach was performed to compare the efficacy and safety of treatments. The surface under the cumulative ranking curve (SUCRA) was calculated for the probability of each treatment as the most effective. The overall response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), adverse events (AEs) grade ≥3, and serious adverse events (SAEs) were evaluated.ResultsOne hundred two publications with 36,147 participants were assigned to 39 different treatments. Among 11 treatments with full information on six outcomes, FOLFIRI/FOLFOX/FOLFOXIRI + bevacizumab significantly improved both the ORR and DCR, compared to FOLFIRI. Although FOLFOX and FOLFIRI/FOLFOX + cetuximab significantly prolonged both OS and PFS, treatments were comparable in terms of AEs grade ≥3 and SAEs. The top highest SUCRA values were observed in the FOLFOXIRI + panitumumab group for ORR (96%) and DCR (99%), FOLFIRI + bevacizumab + panitumumab group for OS (62%) and PFS (54%), and FOLFOXIRI + bevacizumab group for AEs grade ≥3 (59%) and SAEs (59%) outcomes.ConclusionsThese findings suggest an available range of systemic treatment therapies with different efficacy and safety profiles with patients. Further investigations of the side effects and mutation status are required to confirm our findings.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42019127772

Systematic review: predictive value of organoids in colorectal cancer

“…4 ) shows a pooled PPV of 68% (95% CI 0.61–0.72) and NPV of 78% (95% CI 0.72–0.82). The combined response rate of patients in our included studies was 47%, which matches clinically observed response rates in meta-analyses of standard colon cancer therapy 46 . This means that using organoids to guide treatment decisions could significantly increase response rates.…”

Adjuvant Effect of Cinnamon Polyphenolic Components in Colorectal Cancer Cell Lines

“…Interestingly, fraction B from BCHE extract was able to reduce cell viability to almost 50% in the absence of cetuximab and was found to have the same antiproliferative effect at doses of cetuximab between 1 and 10 µg/mL. This finding suggests a potentially very interesting use of cinnamon extracts enriched in polyphenols in chemotherapy, allowing one to reduce cetuximab doses, leading to a decrease in its toxic side effects as well [28]. Notably, procyanidins can also exert an immunosuppressive effect, mainly attributed to the inhibition of T cell functions by A-type procyanidins [29].…”

Dual-targeting peptides@PMO, a mimetic to the pro-apoptotic protein Smac/DIABLO for selective activation of apoptosis in cancer cells

“…To demonstrate that the cytotoxic effect of SS35 was not restricted to HeLa cells but can be expanded to other αvβ3-positive cancer cells, we adopted a panel of three colorectal cancer (CRC) cell lines, Ht-29, HCT-116, and SW480, that were previously described for having increasing expression levels of αvβ3: Ht-29 << HCT-116 < SW480 ( Chin et al 2019 ; Lei et al, 2011 ; Figure 7D ). FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin) is the most commonly used neoadjuvant and adjuvant chemotherapy regimen for advanced colorectal cancers (CRC), and resistance to OxPt was observed in non-responsive patients ( Hoang et al 2022 ). Targeting αvβ integrins proved to be effective in potentiating OxPt effects in CRC cells ( Dia and de Meija 2011 ).…”