Dataset Information

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.

SUBMITTER: Walter T

PROVIDER: S-EPMC7467965 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Walter Thomas T Hawkins Neil S NS Pollock Richard F RF Colaone Fabien F Shergill Suki S Ross Paul J PJ

Journal of cancer research and clinical oncology 20200727 10

<h4>Background</h4>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.<h4>Methods</h4>An SLR was conducted to identify studies co ...[more]

PMID: 32715436

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Project description:BackgroundThe objective of this study is to evaluate the efficacy and safety of different third-line treatment regimens for metastatic colorectal cancer (mCRC) through a comprehensive analysis and network meta-analysis (NMA). Additionally, the study aims to provide guidance on selecting appropriate third-line systemic treatment regimens for patients with mCRC.MethodsWe conducted a search of the PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials databases from January 1, 2005, to May 20, 2023, to include phase II/III randomized clinical trials (RCTs) of third-line treatments for mCRC. The primary outcome assessed in the NMA was median overall survival (mOS), and other outcomes included median progression-free survival (mPFS), disease control rate (DCR), and grade 3 or higher adverse events (≥3AEs).ResultsUltimately, nine phase II/III RCTs involving five treatment regimens were included in this study. Trifluridine/tipiracil (TAS-102) plus bevacizumab (hazard ratio [HR] 0.41, 95% credible interval [CrI] 0.32-0.52) was found to be the most effective treatment for mOS compared to best supportive care (BSC). TAS-102 plus bevacizumab also significantly improved mPFS compared to BSC (HR 0.20, 95% CrI 0.16-0.25). In terms of adverse events (AEs), TAS-102 (RR 0.52, 95% CrI 0.35-0.74) had a lower incidence of ≥3AEs compared to fruquintinib, but fruquintinib (RR 1.79, 95% CrI 1.10-3.11) showed better improvement in DCR than TAS-102. Subgroup analysis using the Bayesian surface under the cumulative ranking curve (SUCRA) ranked the regimens based on the OS benefit. The results indicated that TAS-102 plus bevacizumab ranked first across age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), and time from initial diagnosis of metastatic disease to randomization.ConclusionTAS-102, fruquintinib, TAS-102 plus bevacizumab, the regorafenib standard dose regimen (regorafenib), and the regorafenib dose-escalation regimen (regorafenib 80+) all demonstrated improved OS and PFS compared to BSC in mCRC patients. However, TAS-102 plus bevacizumab may be the optimal choice for third-line treatment in mCRC patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php, CRD42023434929.

Project description:BackgroundAlthough various third-line treatments of advanced gastric cancer (AGC) significantly improved the overall survival, the optimal regimen has not been determined by now. This study aims to evaluate the efficacy and safety of multiple third-line treatments of AGC via integrated analysis and network meta-analysis (NMA) to provide valuable evidence for the optimal third-line systemic therapy for AGC.MethodsBy searching the databases of PubMed, Embase and the Cochrane Central Register of Controlled Trials from Jan 01, 2005 to Dec 31, 2020, we included phase II/III randomized clinical trials (RCTs) of the third-line treatments for AGC to perform NMA. The main outcomes for NMA were median overall survival (mOS), median progression-free survival (mPFS), disease control rate (DCR) and adverse events (AEs). We also included phase IB/II non-RCTs and II/III RCTs of the third-line immune checkpoint inhibitors (ICIs) for integrated analysis for pooled mOS (POS), pooled mPFS (PPFS) and other outcomes.ResultsEight phase II/III RCTs and 2 ICIs-related phase IB/II non-RCTs were included for analysis, involving 9 treatment regimens and 3012 AGC patients. In terms of mOS, apatinib (hazard ratio [HR] 0.61, 95% credible interval [CrI] 0.48-0.78) and nivolumab (HR 0.62, 95% CrI 0.51-0.76) were the most effective treatments compared with placebo. Apatinib also significantly improved mPFS versus placebo (HR 0.38, 95% CrI 0.29-0.49). Nivolumab ranked first among all regimens for 1-year OS rate and achieved the best OS in patients with HER-2 positive tumor, patients with gastroesophageal junction (GEJ) cancer and patients without gastrectomy history. TAS-102 (OR 7.46, 95% CrI 4.61-12.51) was the most toxic treatment in terms of AEs of grade 3 and higher (≥3 AEs). Pembrolizumab was more likely to cause immune related adverse event. Finally, the POS, pooled 1-year OS rate, pooled ORR and PPFS of AGC patients treated with third-line ICIs were 5.1 months, 25%, 10% and 1.71 months respectively.ConclusionsApatinib and nivolumab are the most effective treatments for the third-line treatment of AGC in contrast to the third-line chemotherapy. For AGC patients with HER-2 positive tumor, patients with GEJ cancer and patients without gastrectomy history, ICIs could be the optimal third-line treatment choice.

Project description:BackgroundMany options for third-line treatment of advanced gastric cancer (GC) or gastroesophageal junction carcinoma (GEJC) have been developed. Therapies including immunotherapy (nivolumab), chemotherapy (irinotecan, FTD/TPI), targeted therapy (apatinib), and antibody drug conjugates (ADC) have shown to increase the survival rates in patients, but few studies have compared the relative efficacy of these treatments. Here, we compared the efficacies of these regimens using network meta-analysis (NMA) to provide guides in selecting the best regimen and formulating a precise individualized treatment plan.MethodsThe published RCTs of phase II/III in PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched. The median overall survival (mOS) was the primary outcome of NMA, and the other outcomes were median progression-free survival (mPFS), disease control rate (DCR) (proportion of patients with confirmed CR, PR, or stable disease (SD)) and incidence of grade 3 or above adverse events (≥3AEs).ResultsFive phase II/III RCTs involving 1674 patients and 7 treatment regimens were analyzed. It showed that Trastuzumab Deruxtecan (DS-8201) prolonged the OS of patients significantly comparing with chemotherapy (HR: 0.59; 95% CI: 0.39-0.89) for the overall population. DS-8201 (HR: 0.27; 95% CI: 0.17-0.42) and chemotherapy (HR: 0.57; 95% CI: 0.47-0.7) improved the PFS significantly over nivolumab. Apatinib (RR: 3.04; 95% CI: 1.65-5.95) and DS-8201 (RR: 2.67; 95% CI: 1.51-4.83) were more effective than nivolumab in improving DCR. DS-8201 achieved greater OS benefits compared to chemotherapy (HR: 0.59; 95% CI: 0.39-0.88) for patients who were HER2-positive. We ranked the Bayesian surface under the cumulative ranking curve according to OS benefit, and showed that ADC ranked first for the general patient population and for patients with a HER2-positive diagnosis, intestinal histopathology, previous gastrectomy history, gastric origination cancer, ages over 65 and ECOG PS=0/1, followed by nivolumab and apatinib. For patients with GEJC, nivolumab ranked first.ConclusionsNivolumab, apatinib, chemotherapy, and ADC all improved the OS of GC/GEJC patients significantly. ADC may be the best option for the overall population of GC, as well as for patients with HER2-overexpression, intestinal histopathology, previous gastrectomy history, gastric origination cancer, ages over 65 and ECOG PS=0/1, followed by nivolumab and apatinib. Nivolumab may be the first treatment option for GEJC patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022364714.

Project description:ImportanceMultiple systemic treatments are available for metastatic castration-sensitive prostate cancer (mCSPC), with unclear comparative effectiveness and safety and widely varied costs.ObjectiveTo compare the effectiveness and safety determined in randomized clinical trials of systemic treatments for mCSPC.Data sourcesBibliographic databases (MEDLINE, Embase, and Cochrane Central), regulatory documents (US Food and Drug Administration and European Medicines Agency), and trial registries (ClinicalTrials.gov and European Union clinical trials register) were searched from inception through November 5, 2019.Study selection, data extraction, and synthesisEligible studies were randomized clinical trials evaluating the addition of docetaxel, abiraterone acetate, apalutamide, or enzalutamide to androgen-deprivation therapy (ADT) for treatment of mCSPC. Two investigators independently performed screening. Discrepancies were resolved through consensus. A Cochrane risk-of-bias tool was used to assess trial quality. Relative effects of competing treatments were assessed by bayesian network meta-analysis and survival models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used.Main outcomes and measuresOverall survival, radiographic progression-free survival, and serious adverse events (SAEs).ResultsSeven trials with 7287 patients comparing 6 treatments (abiraterone acetate, apalutamide, docetaxel, enzalutamide, standard nonsteroidal antiandrogen, and placebo/no treatment) were identified. Ordered from the most to the least effective determined by results of clinical trials, treatments associated with improved overall survival when added to ADT included abiraterone acetate (hazard ratio [HR], 0.61; 95% credible interval [CI], 0.54-0.70), apalutamide (HR, 0.67; 95% CI, 0.51-0.89), and docetaxel (HR, 0.79; 95% CI, 0.71-0.89); treatments associated with improved radiographic progression-free survival when added to ADT included enzalutamide (HR, 0.39; 95% CI, 0.30-0.50), apalutamide (HR, 0.48; 95% CI, 0.39-0.60), abiraterone acetate (HR, 0.51; 95% CI, 0.45-0.58), and docetaxel (HR, 0.67; 95% CI 0.60-0.74). Docetaxel was associated with substantially increased SAEs (odds ratio, 23.72; 95% CI, 13.37-45.15), abiraterone acetate with slightly increased SAEs (odds ratio, 1.42; 95% CI, 1.10-1.83), and other treatments with no significant increase in SAEs. Risk of bias was noted for 4 trials with open-label design, 3 trials with missing data, and 2 trials with potential unprespecified analyses.Conclusions and relevanceIn this network meta-analysis, as add-on treatments to ADT, abiraterone acetate and apalutamide may provide the largest overall survival benefits with relatively low SAE risks. Although enzalutamide may improve radiographic progression-free survival to the greatest extent, longer follow-up is needed to examine the overall survival benefits associated with enzalutamide.

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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