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

Abstract

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.

Efficacy of neoadjuvant CapeOX/mFOLFOX6 without radiation for patients with baseline resectable mid–low locally advanced rectal cancer

“…23 On the other hand, several studies have shown controversial results regarding whether CapeOX plus radiation and monoclonal antibody could lead to a better survival without more adverse events. [24][25][26] In this study, no statistically significant difference in pCR (6.25% vs 8.33%, P = 1.000) or ORR (50.00% vs 58.33%, P = 0.682) was noted between CapeOX and mFOLFOX6. Interestingly, although the treatment duration was shorter for four-cycle mFOLFOX6 compared with four-cycle CapeOX (2 months vs 3 months), mFOLFOX6 achieved better TRG compared with CapeOX.…”

Neoadjuvant Chemotherapy plus Bevacizumab Combined with Total Mesorectal Excision in Treating Locally Advanced Rectal Cancer Patients with BRAF Mutation: Clinical Benefit and Safety

“…Finally, it was confirmed that the neoadjuvant treatment of NAC plus bevacizumab has good safety and the patient's survival conditions are also ideal. Another meta-analysis also reached a similar conclusion, supporting that the addition of bevacizumab in NAC has ideal safety while improving the efficacy [ 18 ]. In summary, adding bevacizumab to NAC may be a safe and feasible preoperative option for neoadjuvant therapy in LARC.…”

Current status of total neoadjuvant therapy for locally advanced rectal cancer

“…A recent meta-analysis showed that the pooled pCR rate for TNT-relevant cohorts of LARC patients was 33%. 76 Another recent meta-analysis of randomized trials of LARC by Riesco-Martinez et al 77 showed that compared with standard nCRT, TNT significantly improved pCR rate (13.3% vs. 23.5%, p < 0.001), the 3-year DFS, and the 3-year OS, although the rates of G3/4 AEs and R0 resection were not significantly different. Kasi et al 78 79 showed that TNT compared with standard nCRT did not increase 30-day postoperative mortality (p = 1.0), re-admissions (p = 0.82), or length of hospital stay.…”

“…showed that LARC patients who received TNT followed by surgery had a 5‐year OS of 74.4%, a 5‐year DFS of 65.4%, a weighted mean LR of 3.5% (range 0%–7%), and a DM rate of 20.6% (range 5%–31%). A recent meta‐analysis showed that the pooled pCR rate for TNT‐relevant cohorts of LARC patients was 33% 76 . Another recent meta‐analysis of randomized trials of LARC by Riesco‐Martinez et al 77 .…”