The efficacy and safety of adding bevacizumab in neoadjuvant therapy for locally advanced rectal cancer patients: A systematic review and meta-analysis

Background: Patients with locally advanced rectal cancer (LARC) are more likely to suffer local recurrence and distant metastases, contributing to worse prognoses. Considering the provided dramatic reduction of local recurrences, neoadjuvant CRT (nCRT) followed by curative resection with total mesorectal excision (TME) and adjuvant chemotherapy has been established as standard therapy for LARC patients. However, the efficacy of adding bevacizumab in neoadjuvant therapy, especially in induction therapy-containing nCRT for LARC patients remains uncertain. Materials: PubMed, Embase, and Web of Science were searched to retrieve records on the application of bevacizumab in a neoadjuvant setting for LARC patients. The endpoints of interest were pCR and the rates of patients suffering Grade 3/4 bevacizumab-specific adverse events, namely bleeding, wound healing complications, and gastrointestinal perforation. Results: 29 cohorts covering 1134 subjects were included in this systematic review. The pooled pCR rate for bevacizumab-relevant cohorts was 21% (95% confidence interval (95% CI), 17-25%; I-2 = 61.8%), the pooled estimates of Grade 3/4 bleeding, Grade 3/4 wound healing complication, Grade 3/4 gastrointestinal perforation were 1% (95% CI, 0-3%; I-2 = 0%), 2% (95% CI, 1-5%; I-2 = 4.7%), and 2% (95% CI, 0-5%; I-2 = 0%), respectively. Conclusion: The addition of bevacizumab in the nCRT, especially in the TNT, for LARC patients provides promising efficacy and acceptable safety. However, the results should be interpreted cautiously due to the small amount of relevant data and need further confirmation by future studies.

Automated summary

The addition of bevacizumab in the neoadjuvant chemoradiotherapy, especially in the total neoadjuvant treatment, for locally advanced rectal cancer patients shows promising efficacy and acceptable safety. The pooled pathological complete response rate for bevacizumab-relevant cohorts was 21%, with low rates of Grade 3/4 bevacizumab-specific adverse events. However, caution should be taken in interpreting the results due to the limited amount of relevant data and further confirmation by future studies is needed.