(80) Comparative Effectiveness and Safety of First-Line Treatments of Metastatic Colorectal Cancer in Real-World Settings: A Systematic Review and Meta-Analysis

Publication Number: 754

Background: Comparative effectiveness analysis is critical for informed decision-making in the context of metastatic colorectal cancer (mCRC) which involves multiple treatment strategies. Randomized clinical trials are not always aligned with clinical practice, and greater use of real-world (RW) studies can inform health care decision by providing results that reflect RW practice.

Objectives: The aim of this systematic review and meta-analysis was to provide a synthesis of the available RW evidence on the effectiveness and safety of first-line systemic anti-cancer therapies (SACTs) in patients with mCRC.

Methods: Relevant databases were searched from inception until July 2021. Inclusion criteria were: observational studies; published in English; patients ≥ 18 years; unresectable mCRC; receiving a first-line SACT for treatment of mCRC. The primary effectiveness outcome was overall survival. Safety was assessed by the occurrence of severe adverse events. The results were synthesized using the random-effect meta-analysis model based on hazard ratio and 95% confidence interval (95% CI) for survival outcomes, while risk ratio and 95% CI was used for safety outcomes. Subgroup analysis was performed to explore differences between different treatment strategies. Heterogeneity was assessed using I2 statistic.

Results: The search strategy identified 5662 studies of which 29 met the inclusion criteria and were included in the effectiveness meta-analysis. The pooled hazard ratio for overall survival including all SACTs was 1.14 (95% CI 1.05-1.24). The overall heterogeneity of included studies was 76.2%. Subgroup analysis identified a significant difference between different treatment comparisons (p =0.01). The pooled overall survival was significant for 1 subgroup comparing chemotherapy only versus Bevacizumab+ chemotherapy (pooled estimate: 1.36 (1.18-1.56).
For the safety outcomes, 13 studies were included in the meta-analysis. The pooled relative risk of hematological and non-hematological toxicities was 1.25 (0.89-1.76), 1.07 (0.73-1.54), respectively with no statistically significant difference between different treatment strategies (p > 0.05). The overall heterogeneity of included studies for both haematological and non-haematological toxicities was 85.5%.

Conclusions: The results indicated a survival benefit for bevacizumab with no evidence of additional toxicity when compared to the other regimens used in first-line settings for mCRC. Although this benefit may appear clinically modest, bevacizumab offers hope for increased survival for patients with mCRC.