Safety and Efficacy of Atezolizumab in Ovarian Cancer

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Abstract Introduction Although the efficacy of PD-L1 blockade has been evaluated in analyses that combine pharmacologically distinct antibodies, the specific efficacy and safety of atezolizumab remain unclear. This review aimed to evaluate the efficacy and safety profile of atezolizumab specifically. Methods PubMed/MEDLINE and CENTRAL were searched (June 2026) for phase I to III trials of atezolizumab in ovarian cancer, reported in full-text English with at least 10 evaluable patients. Randomized and single-arm designs qualified. Randomized comparisons were pooled under random-effects models with Knapp-Hartung adjustment as hazard ratios for survival and risk ratios for response and safety; single-arm rates were pooled as proportions using generalized linear mixed models. Heterogeneity was assessed with I², Cochran Q, and prediction intervals, with leave-one-out sensitivity analysis. Analyses used R 4.6.0. Results Twelve studies (13 reports) enrolled 3,179 patients. Atezolizumab reduced the hazard of progression (HR 0.88, 95% CI 0.83 to 0.93) and death (HR 0.86, 95% CI 0.78 to 0.96), without heterogeneity (I² = 0%), whereas objective response was unchanged (RR 0.88, 95% CI 0.52 to 1.49). Excess toxicity was immune-mediated, raising serious adverse events (RR 1.32, 95% CI 1.05 to 1.67), any-grade immune-related events (RR 1.57, 95% CI 1.12 to 2.20), and grade ≥3 immune-related events (RR 2.23, 95% CI 1.05 to 4.74). Conclusion Atezolizumab adds a small survival benefit to a chemotherapy or bevacizumab backbone, driven by delayed progression rather than tumor regression. Offset by doubled immune toxicity and inseparable from its backbone, the effect may not justify routine use. Introduction Ovarian cancer (OC) is the most lethal gynecologic malignancy, marked by late-stage presentation and a high propensity for recurrence [1]. An estimated 313,959 new cases and 207,252 deaths occurred worldwide in 2020 [2], and 5-year survival for advanced disease remains near 17% [3]. Ovarian carcinoma comprises five histological subtypes, of which high-grade serous carcinoma predominates at 70%, followed by endometrioid and clear cell carcinoma at 10% each; most tumors are high-grade lesions that behave aggressively and present at an advanced stage [4]. Programmed cell death protein 1 (PD-1) is a key immune checkpoint receptor that regulates the immune response and maintains self-tolerance, and cancer cells co-opt this pathway to escape immune surveillance [5]. On activated T cells, PD-1 engages the ligands PD-L1 (programmed death-ligand 1) and PD-L2 (programmed death-ligand 2); tumors upregulate PD-L1 to suppress T-cell function and avoid destruction [6]. In OC, PD-L1 is expressed on tumor cells and tumor-infiltrating lymphocytes in more than half of patients, and higher CD8-positive lymphocyte density correlates with longer overall survival, providing a mechanistic rationale for blockade of this axis [3]. Atezolizumab, also designated MPDL3280A, is a monoclonal immunoglobulin G antibody that binds and inhibits PD-L1 [7]. Blockade of PD-L1 operates within a broader landscape of immunotherapeutic and molecularly targeted strategies, which includes T-cell-engaging agents and tyrosine kinase inhibitors [8,9]. Evidence for PD-1/PD-L1 blockade in OC derives largely from studies that combine antibodies with distinct molecular targets and pharmacologic profiles [10]. Atezolizumab enters such pooled estimates through only a limited number of studies [2], and its efficacy and safety in this setting remain poorly characterized relative to agents examined on their own [11]. This systematic review and meta-analysis study addresses that gap by focusing on the safety and efficacy of the addition of atezolizumab to standard therapy. Methods Study design This systematic review and meta-analysis evaluated the safety and efficacy of atezolizumab in OC. The review was designed, conducted, and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Data sources and search strategy PubMed/MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify studies evaluating atezolizumab in ovarian cancer. PubMed was searched on June 28, 2026, using the following string: ("Ovarian Neoplasms"[MeSH] OR "ovarian cancer"[tiab] OR "ovarian carcinoma"[tiab] OR "ovarian tumor"[tiab] OR "ovarian tumour"[tiab] OR "ovarian malignancy"[tiab] OR "epithelial ovarian"[tiab] OR "EOC"[tiab] OR "high-grade serous"[tiab] OR "HGSOC"[tiab] OR "primary peritoneal carcinoma"[tiab] OR "fallopian tube neoplasm"[tiab]) AND ("Atezolizumab"[MeSH] OR "atezolizumab"[tiab] OR "MPDL3280A"[tiab] OR "Tecentriq"[tiab] OR "anti-PD-L1"[tiab] OR "PD-L1 inhibitor"[tiab] OR "PD-L1 blockade"[tiab] OR "PD-L1 antibody"[tiab] OR "CD274"[tiab] OR "B7-H1"[tiab] OR "immune checkpoint inhibitor"[tiab] OR "Immune Checkpoint Inhibitors"[MeSH]). The CENTRAL search was conducted on June 29, 2026, restricted to title and abstract: (atezolizumab) AND ("ovarian cancer" OR ovary OR ovaries). No date, language, publication type, or other limits were applied to either search. Eligibility criteria Eligibility followed a pre-specified PICOS (Population, Intervention, Comparator, Outcomes, Study design) framework, with inclusion and exclusion criteria specified for each element. Population. Eligible studies enrolled patients with OC of any histological subtype (epithelial, high-grade serous, clear cell, endometrioid, primary peritoneal, or fallopian tube carcinoma), with no restriction on age, performance status, BRCA (breast cancer susceptibility gene) status, or line of therapy. Studies were excluded when OC patients could not be separated from a mixed-tumor population, when fewer than 10 evaluable OC patients were reported, or when populations overlapped, in which case the most complete report was retained. Intervention. The intervention was atezolizumab-based therapy at any dose or route, given as monotherapy or in combination with any other agent. Studies without an atezolizumab-containing arm extractable separately were excluded. Comparator. Any comparator was eligible, whether placebo, standard of care, or an active agent, as were single-arm studies with no comparator. Outcomes. Eligible studies reported at least one efficacy outcome (progression-free survival (PFS), overall survival (OS), or objective response rate (ORR)) or one safety outcome (adverse events (AE)s, serious AEs, treatment-related AEs, immune-related AEs (irAE)s, AE-related treatment discontinuation, or treatment-related deaths). Studies without extractable data for any pre-specified outcome were excluded. Study design. Eligible designs were Phase II and III trials (randomized or single-arm) and Phase I/Ib trials reporting efficacy or safety data from an expansion cohort, limited to full-text original articles published in English with no date restriction. Preclinical studies, case reports, editorials, commentaries, narrative reviews, and conference abstracts were excluded, as were non-English or non–full-text publications and publications in non-recommended journals, in line with published guidance for identifying such venues [12]. Study selection process Titles and abstracts were first screened in bulk for OC relevance, presence of an atezolizumab arm, clinical study design, and eligible publication type, with the remaining criteria applied at full-text review. Two researchers independently screened the titles and abstracts of all identified records against the predefined inclusion and exclusion criteria. Studies passing this stage underwent full-text assessment by the same reviewers. Disagreements over eligibility were resolved by a third researcher. Data items and data extraction For each eligible study, data were extracted per treatment arm, covering study identification, population characteristics, intervention and comparator, and efficacy and safety outcomes. Efficacy

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