Efficacy and safety of atezolizumab combined with bevacizumab-based chemotherapy in advanced malignancies: a systematic review and meta-analysis of randomized trials

The integration of immune checkpoint inhibitors with anti-angiogenic therapy has transformed the management of advanced malignancies. Atezolizumab (ATZ), a PD-L1 inhibitor, combined with Bevacizumab (BEV) and chemotherapy, may exert synergistic antitumor effects via immune activation and vascular normalization. However, the comparative efficacy and safety of this triplet regimen across cancer types remain uncertain. A systematic search of PubMed, Embase, Scopus, the Cochrane Library, and major clinical trial registries was conducted from inception to July 31, 2025, to identify randomized controlled trials (RCTs) evaluating ATZ + BEV + chemotherapy versus BEV + chemotherapy alone. Primary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Safety outcomes encompassed all-grade and grade III-IV adverse events based on CTCAE. Pooled risk ratios (RRs) and hazard ratios (HRs) were calculated using a random-effects model. Evidence certainty was assessed via GRADE. A total of eight RCTs comprising 3,707 participants were analyzed. Incorporation of ATZ into the treatment protocol led to a notable increase in ORR (RR = 1.10; 95% CI: 1.00–1.21) and produced significant gains in both PFS (adjusted HR = 0.73; 95%CI: 0.63–0.84) and OS (adjusted HR = 0.83; 95%CI: 0.76–0.92). In contrast, changes in DCR were modest and did not achieve statistical significance (RR = 1.02; P = 0.324). The addition of ATZ did not substantially elevate the frequency of most adverse events relative to BEV plus chemotherapy alone. However, a statistically significant increase was observed in diarrhea (RR = 1.24; 95%CI: 1.06–1.46), predominantly driven by low-grade events, and in grade III-IV nausea (RR = 1.66; 95%CI: 1.03–1.84). Rates of other grade III-IV toxicities were generally comparable between treatment groups. Sensitivity analyses and assessments for publication bias supported the stability of the results, and the overall certainty of the evidence was judged to be high. The ATZ + BEV + chemotherapy regimen demonstrated OS benefits in multiple malignancies, although the magnitude of benefit appears to vary across tumor types. Toxicity was generally manageable, although selective increases in low-grade gastrointestinal events and grade III-IV nausea were observed. Immune-related adverse event profiles differed among indications. These findings support the biologic rationale for concurrent immune and angiogenic targeting; however, tumor-specific factors should be considered when integrating this strategy into contemporary oncology practice. Future biomarker-driven studies are warranted to refine patient selection and optimize therapeutic sequencing.