Dataset Information

Network Meta-analysis of First-Line Systemic Treatment for Patients With Metastatic Colorectal Cancer.

ABSTRACT:

Purpose

To assess the relative efficacy and safety of first-line systemic therapies in patients with metastatic colorectal cancer.

Experimental design

A comprehensive literature review was conducted including MEDLINE, Embase, and the Cochrane Central Registry of Controlled Trials for phase II or III randomized controlled trials (RCTs) published up to and including July 15, 2019. We included RCTs in which at least 1 intervention was either chemotherapeutic agents (such as fluorouracil, irinotecan, or oxaliplatin) or antibodies targeting angiogenesis (such as bevacizumab) or agents that act on the epidermal growth factor receptor pathway (such as cetuximab and panitumumab) or studies reported at least one of the following outcomes: overall survival (OS), progression-free survival (PFS), and/or Grade 3 + adverse events (AEs). Using a random effect model, we performed a Bayesian network meta-analysis to analyze the probability of optimal therapeutic regime obtained from direct comparisons with indirect evidences. We estimated hazard ratios for OS and PFS.

Results

A total of 30 RCTs comprising 12,146 mCRC patients with 25 different treatment strategies were included. The triple combination FOLFOXIRI [fluorouracil, leucovorin, oxaliplatin, and irinotecan] plus bevacizumab provided significant survival benefits with improved OS over all other treatments. The network meta-analysis also indicated a significant advantage of using FOLFOXIRI plus bevacizumab in comparison to other treatment strategies for PFS. Besides, FOLFOXIRI plus bevacizumab was associated with the well-tolerated adverse events.

Conclusions

Our study supported the use of FOLFOXIRI plus bevacizumab as the best first-line regimen and potentially effective and safe strategy for the management of patients with mCRC.

SUBMITTER: Xu S

PROVIDER: S-EPMC8474314 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThe effectiveness of triplet therapy compared with androgen pathway inhibitor (API) doublets in a heterogeneous patient population with metastatic castration-sensitive prostate cancer (mCSPC) is unknown.ObjectiveTo assess the comparative effectiveness of contemporary systemic treatment options for patients with mCSPC across clinically relevant subgroups.Data sourcesFor this systematic review and meta-analysis, Ovid MEDLINE and Embase were searched from each database's inception (MEDLINE, 1946; Embase, 1974) through June 16, 2021. Subsequently, a "living" auto search was created with weekly updates to identify new evidence as it became available.Study selectionPhase 3 randomized clinical trials (RCTs) assessing first-line treatment options for mCSPC.Data extraction and synthesisTwo independent reviewers extracted data from eligible RCTs. The comparative effectiveness of different treatment options was assessed with a fixed-effect network meta-analysis. Data were analyzed on July 10, 2022.Main outcomes and measuresOutcomes of interest included overall survival (OS), progression-free survival (PFS), grade 3 or higher adverse events, and health-related quality of life.ResultsThis report included 10 RCTs with 11 043 patients and 9 unique treatment groups. Median ages of the included population ranged from 63 to 70 years. Current evidence for the overall population suggests that the darolutamide (DARO) triplet (DARO + docetaxel [D] + androgen deprivation therapy [ADT]; hazard ratio [HR], 0.68; 95% CI, 0.57-0.81), as well as the abiraterone (AAP) triplet (AAP + D + ADT; HR, 0.75; 95% CI, 0.59-0.95), are associated with improved OS compared with D doublet (D + ADT) but not compared with API doublets. Among patients with high-volume disease, AAP + D + ADT may improve OS compared with D + ADT (HR, 0.72; 95% CI, 0.55-0.95) but not compared with AAP + ADT, enzalutamide (E) + ADT, and apalutamide (APA) + ADT. For patients with low-volume disease, AAP + D + ADT may not improve OS compared with APA + ADT, AAP + ADT, E + ADT, and D + ADT.Conclusions and relevanceThe potential benefit observed with triplet therapy must be interpreted with careful accounting for the volume of disease and the choice of doublet comparisons used in the clinical trials. These findings suggest an equipoise to how triplet regimens compare with API doublet combinations and provide direction for future clinical trials.