Comparative effectiveness and safety of first-line systemic anti-cancer treatments of metastatic colorectal cancer : a systematic review and meta-analysis

Yasin, Haya and Kurdi, Amanj and Mahmoud, Fatema and Weir, Natalie and Mueller, Tanja and Bennie, Marion (2022) Comparative effectiveness and safety of first-line systemic anti-cancer treatments of metastatic colorectal cancer : a systematic review and meta-analysis. In: British Oncology Pharmacy Association (BOPA) 2022 – 25th Annual Symposium, 2022-10-07 - 2022-10-09, Liverpool.

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Abstract

Background: metastatic colorectal cancer (mCRC) is characterised by multiple treatment strategies. Randomised clinical trials are not always aligned with the clinical practice, and greater use of realworld (RW) studies has been suggested to inform health care decisions by providing results that reflect RW practice. The purpose 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; mCRC; first-line SACT for treatment of mCRC. No restrictions were placed on the country of publication. The effectiveness outcomes included overall survival (OS), the primary outcome, and progression-free survival (PFS). Safety was assessed by the occurrence of grade 3 or 4 adverse effects based on the national cancer institute common terminology criteria for adverse events (NCI CTCAE). The results were synthesised using a randomeffect 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 outcome. Subgroup analysis was performed to explore differences between different treatment strategies. Heterogeneity was assessed using I2. Results: The search strategy identified 5662 studies, of which 31 met the inclusion criteria and were included in the overall survival meta-analysis. The pooled hazard ratio for overall survival, including all SACTs, was 1.19 (1.1-1.29). The overall heterogeneity of included studies was 76.6%. Subgroup analysis identified a significant difference between different treatment comparisons (p =0.01). The pooled overall survival was significant for chemotherapy only versus Bevacizumab+ chemotherapy (pooled estimate: 1.15 (1.05-1.26). For PFS, 20 studies were included in the meta-analysis. The pooled hazard ratio, including all SACTs, was 1.19 (1.08- 1.3), with an overall heterogeneity of the included studies was 64.4%. subgroup analysis showed a significant difference between different comparisons (p=0.001). the pooled PFS was significant for: (1) chemotherapy only versus bevacizumab+ chemotherapy (pooled estimate: 1.36 (1.05-1.26) and (2) bevacizumab+ irinotecan-based chemotherapy versus bevacizumab+ oxaliplatinbased chemotherapy (pooled estimate: 1.22 (1.07-1.38). For the safety outcomes, 14 studies were included in the meta-analysis. The pooled relative risk of haematological and non-haematological toxicities was 1.25 (0.89-1.76) and 1.03 (0.73-1.46), respectively, with no statistically significant difference between different treatment strategies for the haematological toxicities (p > 0.05). However, the pooled estimate for non-haematological toxicities was significant for two subgroups (1) bevacizumab+ XELIRI versus bevacizumab+ FOLFIRI (pooled estimate 1.66 (1.03-2.7). and bevacizumab+ FOLFOXIRI versus bevacizumab+ XELOXIRI (pooled estimate: 3.5 (1.9-6.4). Conclusion: The results indicated a survival benefit for bevacizumab with additional nonhaematological toxicities for several combinations involving bevacizumab used in first-line settings of mCRC treatment. Although the survival benefit may appear clinically modest, bevacizumab offers hope for increased survival for patients with mCRC.

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