Safety and Efficacy of Atezolizumab in Ovarian Cancer

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 outcomes comprised PFS, OS, and objective response and its components, together with disease control rate; safety outcomes comprised any-grade and grade 3 or higher (grade ≥3) AEs, irAEs, treatment discontinuation, and treatment-related deaths. Proportions were recorded as raw event counts and denominators, and hazard ratios (HRs) with 95% confidence intervals (CIs) were taken only from randomized comparisons. The full list of extracted variables is provided in Table S1. Data analysis and synthesis Analyses were performed in R version 4.6.0 using the metafor and glmmTMB packages, and an outcome was pooled only when at least three studies contributed data. Comparative outcomes were drawn from randomized comparisons of atezolizumab added to a backbone regimen versus the same backbone with placebo, and all were pooled with the same random-effects model, using inverse-variance weighting with restricted maximum likelihood estimation of the between-study variance and the Knapp-Hartung adjustment to the confidence interval. Hazard ratios for PFS and OS were entered as log HRs with standard errors, whereas for objective response and the comparative safety outcomes (any-grade AEs, serious adverse events (SAEs), and irAEs, both any grade and grade ≥3) risk ratios (RRs) were computed from event counts, with a 0.5 continuity correction applied to studies with zero-event cells. Single-arm event frequencies in the atezolizumab arm were pooled as proportions for grade ≥3 AEs, treatment-related grade ≥3 AEs, SAEs, adverse-event-related treatment discontinuation, and grade 5 or treatment-related deaths, using a binomial generalized linear mixed model with multiple arms within a study modeled hierarchically where applicable. Heterogeneity was assessed with the I-squared statistic, tau-squared, the Cochran Q test, and prediction intervals, and leave-one-out omission was used as a sensitivity analysis across pooled outcomes if the number of contributing studies was more than 3. Methodological quality assessment Randomized trials were assessed with the Cochrane Risk of Bias 2 (RoB 2) tool across its five domains, with an overall judgment of low risk, some concerns, or high risk. Data sets analyzed as single arms, comprising the single-arm trials and the randomized trials that contributed single-arm data only, were assessed with the non-comparative Methodological Index for Non-Randomized Studies (MINORS), scoring eight items from 0 to 2 for a maximum of 16. Certainty of evidence was rated with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework for each of the fourteen outcomes. The nine comparative outcomes (PFS, PFS [PD-L1-Positive], OS, OS [PD-L1-Positive], ORR, and the any-grade, SAEs, and irAE risk ratios) were graded as effect estimates versus control and, being derived from randomized trials, began at high certainty; the five single-arm outcomes were graded as certainty in a pooled proportion and began at low certainty. Ratings considered risk of bias, inconsistency, indirectness, imprecision, and other considerations, with the risk-of-bias domain drawn from the RoB 2 and MINORS assessments. Evidence was classified as high, moderate, low, or very low certainty. Results Study selection A total of 613 records were identified, comprising 550 from PubMed/MEDLINE and 63 from CENTRAL (Cochrane Central Register of Controlled Trials). After removal of 17 duplicates, 596 records underwent title and abstract screening, of which 565 were excluded. Thirty-one reports were sought for retrieval; one could not be obtained, leaving 30 for full-text assessment. Of these, 17 were excluded: eight lacked an atezolizumab arm, seven were duplicate reports of an already-included study, one had fewer than 10 patients in the atezolizumab arm, and one had fewer than 10 evaluable OC patients separable from a mixed population. Twelve studies, described in 13 reports, met all eligibility criteria and entered the review [13–25] (Figure 1). Study and patient characteristics The 12 included studies enrolled 3,179 patients and were published between 2019 and 2026. By design, 4 (33.3%) were randomized, double-blind, placebo-controlled, 3 (25.0%) randomized, open-label, and 5 (41.7%) single-arm. Four studies (33.3%) were phase III and accounted for 2,906 patients; the remaining eight (66.7%) were phase I to II, comprising 1 (8.3%) phase II, 6 (50.0%) phase Ib or I, and 1 (8.3%) phase I/II. Seven studies were randomized, and five were single-arm (Table 1 & Table 2). Table 1. Individual Study Characteristics. Study Information Population Time-to-event Response Study (author, year) Trial / acronym Population/line Study Arm(s) Phase Design Analysis pool NCT no. N enrolled (ITT) N treated (safety) N evaluable (response) Median PFS (mo) PFS events n PFS HR (95% CI) PFS population Median OS (mo) OS events n OS HR (95% CI) 1-yr PFS % 1-yr OS % ORR n ORR N CR n PR n SD n PD n DCR n DCR N DCR definition Response criteria Banerjee et al. 2025 [13] EORTC 1508-GCG Recurrent, platinum-resistant Arm 4: Bev + atezo + placebo II Randomized, open-label Both (proportion + HR vs Arm 1) NCT02659384 32 31 32 4.1 28 0.84 (0.50–1.38) ITT (vs Arm 1) 12.1 22 0.89 (0.49–1.59) NR NR 6 32 1 5 NR 22 21 32 NR RECIST 1.1 Arm 1: Bev monotherapy (COMPARATOR) II Randomized, open-label HR comparator NCT02659384 33 31 33 2.3 32 NR ITT (reference) 10.4 23 NR NR NR 3 33 0 3 NR 27 21 33 NR RECIST 1.1 Arm 5: Bev + atezo + ASA II Randomized, open-label Proportion (HR shares Arm 1 control; excl. from HR pool) NCT02659384 33 33 33 4 29 0.81 (0.49–1.34) ITT (vs Arm 1) 11.6 22 0.71 (0.39–1.28) NR NR 6 33 1 5 NR 26 22 33 NR RECIST 1.1 Gaillard et al. 2026 [14] AdORN First-line, neoadjuvant + interval surgery Atezolizumab + NACT (wkly pac/carbo) -> maint atezo +/- bev Ib Single-arm / non-randomized Proportion NCT03394885 18 18 15 23.6 8 NR ITT NR NR NR NR NR 9 15 0 9 6 0 15 15 Sum of partial response and stable disease. RECIST 1.1 Gonzalez-Martin et al. 2025 [15] ANITA / ENGOT-OV41 / GEICO 69-O Recurrent (platinum-based) + maintenance niraparib Atezolizumab + platinum CT → Atezolizumab + Niraparib III Randomized, double-blind, placebo-controlled Both (HR + proportion) NCT03598270 208 207 208 11.2 170 0.89 (0.71–1.10) ITT NR NR NR 44 NR 93 207 14 79 91 NR NR NR NR RECIST 1.1 Placebo + platinum CT → Placebo + Niraparib III Randomized, double-blind, placebo-controlled HR comparator NCT03598270 209 209 209 10.1 174 NR ITT NR NR NR 35 NR 90 209 13 79 96 NR NR NR NR RECIST 1.1 Harter  et al. 2026 [16] AGO-OVAR 2.29 / ENGOT-ov34 Recurrent, non-platinum CT Atezolizumab + bev + non-plat CT III Randomized, double-blind, placebo-controlled Both (HR + proportion) NCT03353831 285 281 255 6.4 243 0.87 (0.73–1.04) ITT 14.2 197 0.83 (0.68–1.01) 28 58 101 255 11 90 91 NR NR NR NR NR Placebo + bev + non-plat CT III Randomized, double-blind, placebo-controlled HR comparator NCT03353831 289 286 248 6.7 261 NR ITT 13 221 NR 23 56 108 248 6 102 87 NR NR NR NR NR Kristeleit et al. 2024 [17] COUPLET Platinum-sensitive recurrent, tBRCAmut Part 2 Arm A: rucaparib + atezo, tBRCAmut ovarian Ib Single-arm / non-randomized Proportion NCT03101280 10 10 10 NR NR NR ITT NR NR NR NR NR 6 10 1 5 NR NR NR 10 NR RECIST 1.1 Kurtz et al. 2023 [18] ATALANTE / ENGOT-ov29 Platinum-sensitive recurrent Atezolizumab + bev + platinum CT III Randomized, double-blind, placebo-controlled Both (HR + proportion) NCT02891824 410 408 410 13.5 348 0.83 (0.69–0.99) ITT 35.5 NR 0.81 (0.65–1.01) 56 89 62 410 NR NR NR NR NR NR NR RECIST 1.1 Placebo + bev + platinum CT III Randomized, double-blind, placebo-controlled HR comparator NCT02891824 204 201 204 11.3 187 NR ITT 30.6 NR NR 46 87 66 204 NR NR NR NR NR NR NR RECIST 1.1 Liu et al. 2019 [19] PCD4989g Advanced, monotherapy Atezolizumab monotherapy (ovarian cohort) Ia/I Single-arm / non-randomized Proportion NCT01375842 12 12 9 2.9 NR NR Efficacy evaluable (n=10) 11.3 NR NR 20 41.7 2 9 1 1 0 5 2 9 Percentage of patients with best response of CR, PR or SD for ≥24 weeks RECIST 1.1 Moore et al.  2021 & Pignata et al. 2023 [20, 21]   IMagyn050 / GOG-3015 / ENGOT-OV39   First-line, newly diagnosed stage III/IV   Atezolizumab + carboplatin/paclitaxel + bevacizumab III Randomized, double-blind, placebo-controlled Both (HR + proportion) NCT03038100 651 642 251 19.5 323 0.92 (0.79–1.07) ITT 50.5 254 0.92 (0.78–1.09) NR NR 233 251 NR NR NR NR NR NR NR RECIST 1.1 Placebo + carboplatin/paclitaxel + bevacizumab III Randomized, double-blind, placebo-controlled HR comparator NCT03038100 650 644 239 18.4 341 NR ITT 46.6 278 NR NR NR 212 239 NR NR NR NR NR NR NR RECIST 1.1 Moroney et al. 2020 [22] GP28328 Recurrent ovarian Atezolizumab + bevacizumab Ib Single-arm / non-randomized Proportion NCT01633970 20 20 20 4.9 NR NR Safety evaluable 10.2 NR NR NR 48.75 3 20 0 3 8 5 11 20 ≥12 weeks RECIST 1.1 Mutch et al. 2024 [23] YO40482 Platinum-sensitive recurrent, BRCA-wt Triplet: PARPi + MEKi + atezolizumab Ib Randomized, open-label Both (HR + proportion) NCT03695380 37 37 37 7.4 28 NR ITT NR NR NR NR 73 NR 37 NR NR NR NR NR NR NR RECIST 1.1 Doublet: PARPi + MEKi (no atezo) Ib Randomized, open-label HR comparator NCT03695380 39 39 39 6 28 NR ITT NR NR NR NR 82 NR 39 NR NR NR NR NR NR NR RECIST 1.1 Rocconi et al. 2022 [24] — Relapsed ovarian Atezo-1st I Randomized, open-label Proportion NCT03073526 10 10 10 2.8 NR NR ITT 10.8 NR NR NR NR NR 10 NR NR NR NR NR NR NR RECIST 1.1 Vigil-1st I Randomized, open-label Proportion NCT03073526 11 11 11 3.4 NR 0.76 (0.28–2.00) ITT NR NR 0.33 (0.06–1.70) NR NR NR 11 NR NR NR NR NR NR NR RECIST 1.1 Simonelli et al. 2022 [25] ACT15377 Advanced solid tumors (ovarian cohort) Isatuximab + atezolizumab (OVARIAN subset only) I/II Single-arm / non-randomized Proportion NCT03637764 18 18 18 2.04 NR NR all treated NR NR NR NR NR 1 18 0 1 6 10 7 18 Not Defined RECIST 1.1 Abbreviations: AGO-OVAR, Arbeitsgemeinschaft Gynäkologische Onkologie–Ovarian Cancer Study Group; ASA, acetylsalicylic acid (aspirin); atezo, atezolizumab; bev, bevacizumab; BRCA-wt, BRCA wild-type; carbo, carboplatin; CI, confidence interval; CR, complete response; CT, chemotherapy; DCR, disease control rate; ENGOT, European Network of Gynaecological Oncological Trial groups; EORTC, European Organisation for Research and Treatment of Cancer; GCG, Gynaecological Cancer Group; GEICO, Grupo Español de Investigación en Cáncer de Ovario; GOG, Gynecologic Oncology Group; HR, hazard ratio; ITT, intention-to-treat; maint, maintenance; MEKi, MEK inhibitor; mo, months; NACT, neoadjuvant chemotherapy; NCT, ClinicalTrials.gov registration number; NR, not reported; ORR, objective response rate; OS, overall survival; pac, paclitaxel; PARPi, poly(ADP-ribose) polymerase inhibitor; PD, progressive disease; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; tBRCAmut, tumor BRCA-mutated; wkly, weekly. Table 2. Summary of Study and Patient Characteristics. Characteristic n (%) Study & Trial Characteristics Study Design (N=12)     Randomized, double-blind, placebo-controlled 4 (33.3%)     Randomized, open-label 3 (25.0%)     Single-arm / non-randomized 5 (41.7%) Trial Phase (N=12)     Phase III 4 (33.3%)     Phase II 1 (8.3%)     Phase Ib 4 (33.3%)     Phase I 1 (8.3%)     Phase Ia/I 1 (8.3%)     Phase I/II 1 (8.3%) Patient Baseline Characteristics Histology (N=3118)     High-grade serous 2335 (74.9%)     Low-grade serous 183 (5.9%)     Serous (grade unspecified) 180 (5.8%)     Endometrioid 99 (3.2%)     Clear cell 109 (3.5%)     Seromucinous 32 (1.0%)     Mucinous 17 (0.5%)     Other 163 (5.2%) FIGO Tumor Stage (N=1437)     Stage I 2 (0.1%)     Stage II 4 (0.3%)     Stage III 988 (68.8%)     Stage IV 442 (30.8%)     Unknown / Missing 1 (0.1%) ECOG Performance Status (N=3169)     0 1848 (58.3%)     1 1240 (39.1%)     2 71 (2.2%)     Missing 10 (0.3%) PD-L1 Status (N=2938)     PD-L1 Positive 1314(44.7%)     PD-L1 Negative 1362 (46.4%)     Other (noninformative / missing / unknown) 262 (8.9%) Prior Therapy Lines (N=3168)     No prior therapy (treatment-naive) 1320 (41.7%)     1 prior line/regimen 1033 (32.6%)     2 prior lines/regimens 455 (14.4%)     3 prior lines/regimens 213 (6.7%)     Missing 3 (0.1%)     Other (≥3 / range-reported) 144 (4.5%) Efficacy and Safety Outcomes Response     ORR (objective response) (N=2193) 1001 (45.7%)     Complete response (CR) (N=1089) 48 (4.4%)     Partial response (PR) (N=1089) 382 (35.1%)     Stable disease (SD) (N=981) 385 (39.3%)     Progressive disease (PD) (N=160) 95 (59.4%)     DCR (disease control) (N=160) 99 (61.9%) Worst AE Grade (N=2296)     Grade 1–2 (mild–moderate) 562 (24.5%)     Grade 3–4 (severe, non-fatal) 1700 (74.0%)     Grade 5 (fatal) 22 (1.0%)     Not separable (any-grade only) 12 (0.5%) Abbreviations: AE, adverse event; CR, complete response; DCR, disease control rate; ECOG, Eastern Cooperative Oncology Group; FIGO, International Federation of Gynecology and Obstetrics; ORR, objective response rate; PD, progressive disease; PD-L1, programmed death ligand 1; PR, partial response; SD, stable disease. Enrollment was largely restricted to good functional status. Pooled across studies, 1,848 (58.3%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1,240 (39.1%) a status of 1, and 71 (2.2%) a status of 2. Prior treatment exposure spanned the full disease course: 1,320 patients (41.7%) were treatment-naive, 1,033 (32.6%) had received one prior line, 455 (14.4%) two lines, and 213 (6.7%) three lines. High-grade serous carcinoma predominated, at 2,335 (74.9%) patients of those with reported histology. Among patients with staging data, disease was predominantly advanced, 988 (68.8%) stage III and 442 (30.8%) stage IV. Expression of PD-L1 was positive in 1,314 (44.7%) and negative in 1,362 (46.4%), with 262 (8.9%) noninformative or unknown (Table 2 & Table 3). Table 3. Baseline Demographic and Disease Characteristics of Patients. Study & arm characteristics Histology, n (%) Tumor Stage, n (%) Performance status, n (%)   Prior therapy lines, n (%) Study (year) / trial Arm N High-grade serous Low-grade serous Serous, NOS Endometrioid Clear cell Other / mixed Stage 1 Stage 2 Stage 3 Stage 4 Unknown PS 0 PS 1 PS 2 Missing / other Treatment-naïve 1 line 2 lines ≥3 lines Grouped (as reported) Missing Banerjee et al. 2025 [13] Bev monotherapy (Arm 1) 33 — — 25 (75.8) 0 (0) 3 (9.1) 5 (15.2)* 1 (3.0%) 1 (3.0%) 22 (66.7%) 9 (27.3%) 0 14 (42.4) 19 (57.6) 0 (0) — — — — 28 (84.8) ≤2: 5 (15.2) — Bev + atezo + placebo (Arm 4) 32 — — 28 (87.5) 1 (3.1) 2 (6.3) 1 (3.1) 1 (3.1%) 2 (6.3%) 21 (65.6%) 7 (21.9%) 1 (3.1%) 13 (40.6) 19 (59.4) 0 (0) — — — — 27 (84.4) ≤2: 5 (15.6) — Bev + atezo + ASA (Arm 5) 33 — — 33 (100) 0 (0) 0 (0) 0 (0) 0 (0.0%) 1 (3.0%) 19 (57.6%) 13 (39.4%) 0 23 (69.7) 10 (30.3) 0 (0) — — — — 27 (81.8) ≤2: 6 (18.2) — Gaillard et al. 2026 [14] Atezo + neoadjuvant CT → maint. atezo ± bev 18 18 (100) — — — — — 0 0 13 (72.2%) 5 (27.8%) 0 2 (11.1) 11 (61.1) 5 (27.8) — 18 (100) — — — — — González-Martín et al. 2025 [15] Atezo → atezo + niraparib 208 187 (90) — — 11 (5) — 10 (4.8)* NR NR NR NR NR 132 (63) 73 (35) — Missing 3 (1) — 181 (87) 26 (13) — — 1 (<1) Placebo → placebo + niraparib 209 196 (94) — — 5 (2) — 8 (3.8)* NR NR NR NR NR 123 (59) 82 (39) — Missing 4 (2) — 179 (86) 28 (13) — — 2 (1) Harter et al. 2026 [16] Atezo + bev + non-platinum CT 285 214 (75) 8 (2.8) — 12 (4.2) 17 (6.0) 34 (11.9)* NR NR NR NR NR 163 (57) 120 (42) — Missing 2 (0.7) — 70 (25) 112 (39) 103 (36) — — Placebo + bev + non-platinum CT 289 230 (80) 10 (3.5) — 8 (2.8) 16 (5.5) 25 (8.7)* NR NR NR NR NR 152 (53) 136 (47) — Missing 1 (0.3) — 70 (24) 115 (40) 104 (36) — — Kristeleit et al. 2024 [17] Rucaparib + atezo (Arm A)‡ 10 NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR Kurtz et al. 2023 [18] Atezo + bev + platinum CT 410 346 (84) 32 (8) — 12 (3) 8 (2) 12 (3) NR NR NR NR NR 277 (68) 131 (32) 2 (<1) — — 307 (75) 103 (25) — — — Placebo + bev + platinum CT 204 169 (83) 8 (4) — 11 (5) 9 (4) 7 (3) NR NR NR NR NR 147 (72) 57 (28) 0 (0) — — 159 (78) 45 (22) — — — Liu et al. 2019 [19] Atezo monotherapy 12 NR NR NR NR NR NR NR NR NR NR NR 6 (50.0) 6 (50.0) — — 1 (8.3)‖ 0 (0) — — ≥2: 11 (91.7) — Moore et al. 2021 [20,21] Atezo + carbo/pac + bev 651 504 (77) 67 (10) — 14 (2) 29 (4) 37 (6) 0 0 448 (69%) 203 (31%) 0 355 (55) 263 (40)* 33 (5)* — 651 (100) — — — — — Placebo + carbo/pac + bev 650 489 (75) 58 (9) — 21 (3) 22 (3) 60 (9) 0 0 448 (69%) 201 (31%) 0 353 (54) 266 (41)* 31 (5)* — 650 (100) — — — — — Moroney et al. 2020 [22] Atezo + bev 20 — — 12 (60) 3 (15) 2 (10) 3 (15) NR NR NR NR NR 11 (55) 9 (45) — — — — — 13 (65)* 1–2: 7 (35)§ — Mutch et al. 2024 [23] Cobi + nira + atezo (triplet) 37 — — 31 (84) — — 6 (16) NR NR NR NR NR 25 (78)† 12 (22)† — — — 29 (68) 8 (32) — — — Cobi + nira (doublet) 39 — — 35 (90) — — 4 (10) NR NR NR NR NR 31 (79) 8 (21) — — — 27 (69) 11 (28) — — 1 (3) Rocconi et al. 2022 [24] Atezo first (then Vigil) 10 NR NR NR NR NR NR 0 0 9 (90.0%) 1 (10.0%) 0 2 (20.0) 8 (80.0) — — — 2 (20)§ 3 (30) 5 (50)* — — Vigil first (then atezo) 11 NR NR NR NR NR NR 0 0 8 (72.7%) 3 (27.3%) 0 7 (63.6) 4 (36.4) — — — 5 (45.5)§ 4 (36.4) 2 (18.2)* — — Simonelli et al. 2022 [25] Isatuximab + atezo 18 — — 16 (88.9) 1 (5.6) 1 (5.6) — NR NR NR NR NR 12 (66.7) 6 (33.3) — — — 4 (22.2) — — ≥2: 14 (77.8)§ — Abbreviations: ASA, acetylsalicylic acid; atezo, atezolizumab; bev, bevacizumab; carbo, carboplatin; cobi, cobimetinib; CT, chemotherapy; maint., maintenance; nira, niraparib; NOS, not otherwise specified; NR, not reported; pac, paclitaxel; PS, performance status. Notes affecting how a value reads. *  Percentage recomputed from N (not printed by the trial); all other percentages are as reported. † Mutch triplet: printed performance-status percentages (78 / 22) do not reconcile with n = 37 (25/37 ≈ 68 %, 12/37 ≈ 32 %); shown as printed. ‡ Kristeleit: Arm A not reported separately; values are pooled Part 2 ovarian Arms A + B (n = 14) — e.g., PS 0 = 11 (79), PS 1 = 3 (21); eligibility was 1–2 prior platinum-containing regimens. Counted by the trial as prior regimens rather than lines (Rocconi, Moroney, Simonelli). ‖ Liu: “treatment-naïve” = 0 prior lines (advanced-disease phase Ia setting). ¶ Moore (IMagyn050) baseline is shared with Pignata 2023 (OS/PRO update of the same randomized population) and is listed once. Efficacy Progression-free survival was pooled from five randomized comparisons of atezolizumab added to a backbone regimen versus the backbone with placebo. The pooled HR was 0.88 (95% CI 0.83 to 0.93, p = 0.003), favoring atezolizumab, with no detectable heterogeneity (I² = 0.0%, Q p = 0.94) and a stable estimate across leave-one-out analysis (HR 0.86 to 0.89). In the PD-L1–positive subgroup, progression-free survival was pooled from four randomized comparisons (1297 patients; 686 atezolizumab, 611 control), giving a pooled HR of 0.82 (95% CI 0.76 to 0.89, p = 0.004), likewise favoring atezolizumab, again without heterogeneity (I² = 0.0%, Q p = 0.95) and stable on leave-one-out analysis (HR 0.81 to 0.84) (Figure 2). Overall survival, pooled from four randomized comparisons, gave an HR of 0.86 (95% CI 0.78 to 0.96, p = 0.021), again favoring atezolizumab, without heterogeneity (I² = 0.0%, Q p = 0.79) and consistent on leave-one-out analysis (HR 0.82 to 0.88). In the PD-L1–positive subgroup, overall survival was pooled from three randomized comparisons (1148 patients; 610 atezolizumab, 538 control), giving an HR of 0.83 (95% CI 0.71 to 0.98, p = 0.040), also favoring atezolizumab and without heterogeneity (I² = 0.0%, Q p = 0.85). Leave-one-out analysis was not performed for this outcome, as omitting any single trial would have left fewer than three studies (Figure 3). Objective response, pooled from five randomized comparisons, gave an RR of 0.88 (95% CI 0.52 to 1.49, p = 0.55), showing no significant difference between atezolizumab and control. Unlike the survival endpoints, heterogeneity was substantial (I² = 92.3%, Q p < 0.001), with per-study risk ratios spanning both directions (0.47 to 2.06) and a wide prediction interval (0.25 to 3.15); the pooled estimate ranged from 0.84 to 1.04 on leave-one-out analysis (Figure 4). Safety Adverse event profile The overall AE profile was dominated by events attributable to the chemotherapy and anti-angiogenic backbone, which occurred at similar frequencies in both arms. Common all-grade events included fatigue (42% with atezolizumab vs 41% with control), nausea (52% vs 55%), anemia (43% vs 42%), neutropenia (35% vs 35%), and alopecia (47% vs 51%). Grade ≥3 AEs were predominantly hematologic and comparable between arms, including neutropenia (23% vs 23%), anemia (13% vs 11%), thrombocytopenia (12% vs 12%), and hypertension (14% vs 14%). The excess toxicity associated with atezolizumab was concentrated in immune-related, cutaneous, and endocrine categories. Relative to control arms, atezolizumab-containing arms showed higher rates of rash (23% vs 15%), maculopapular rash (9% vs 3%), pruritus (14% vs 9%), pyrexia (20% vs 10%), hypothyroidism (12% vs 5%), and colitis (3% vs 1%), together with a higher rate of composite immune   mediated events (27% vs 21%), including at grade ≥3 AEs (11% vs 6%) (Table 4). Table 4. Adverse Events in Atezolizumab-containing Versus Non-atezolizumab Arms. Adverse event   Atezolizumab arms Non-atezolizumab arms All grade Grade ≥3 All grade Grade ≥3 General / constitutional Fatigue 531/1261 (42%) 40/1261 (3%)* 495/1209 (41%) 31/1209 (3%)* Asthenia 222/898 (25%) 22/898 (2%)* 217/892 (24%) 19/892 (2%)* Pyrexia / fever 188/925 (20%) 7/945 (1%)* 85/884 (10%) 8/884 (1%)* Decreased appetite / anorexia 132/962 (14%) 34/962 (4%)* 120/923 (13%) 34/923 (4%)* Weight loss 22/82 (27%) 0/82 (0%)* 5/31 (16%) 0/31 (0%) Mucositis / mucosal inflammation 55/308 (18%) 3/308 (1%)* 54/279 (19%) 3/279 (1%)* Peripheral edema 9/64 (14%) 0/64 (0%) 2/31 (6%) 0/31 (0%) Gastrointestinal Nausea 505/980 (52%) 24/1000 (2%)* 510/923 (55%) 8/923 (1%)* Vomiting 252/980 (26%) 29/1000 (3%)* 254/923 (28%) 13/923 (1%)* Diarrhea 441/1249 (35%) 38/1249 (3%)* 379/1209 (31%) 32/1209 (3%)* Constipation 361/950 (38%) 5/950 (1%)* 362/923 (39%) 9/923 (1%)* Abdominal pain 378/1261 (30%) 37/1281 (3%)* 370/1209 (31%) 27/1209 (2%)* GI perforation 7/281 (2%) 6/281 (2%) 12/286 (4%) 12/286 (4%) Ileus 16/673 (2%) 10/673 (1%)* 12/675 (2%) 6/675 (1%)* Colitis 26/923 (3%) 14/923 (2%)* 13/930 (1%) 8/930 (1%)* Hematologic Anemia 545/1261 (43%) 161/1261 (13%)* 503/1209 (42%) 130/1209 (11%)* Neutropenia 421/1194 (35%) 272/1194 (23%)* 410/1170 (35%) 266/1170 (23%)* Febrile neutropenia 64/642 (10%) 64/642 (10%)* 34/644 (5%) 34/644 (5%)* Thrombocytopenia 283/931 (30%) 114/951 (12%)* 267/853 (31%) 106/853 (12%)* Leukopenia / WBC decreased 98/913 (11%) 52/913 (6%)* 101/853 (12%) 42/853 (5%)* Lymphopenia 17/706 (2%) 6/706 (1%)* 7/644 (1%) 3/644 (0%)* Hepatic / metabolic ALT increased 9/82 (11%) 0/82 (0%)* 2/31 (6%) 1/31 (3%) AST increased 51/326 (16%) 1/326 (0%)* 39/279 (14%) 3/279 (1%)* Elevated liver enzymes (composite) 43/281 (15%) 10/281 (4%) 33/286 (12%) 9/286 (3%) Lipase increased 14/101 (14%) 6/101 (6%) 8/70 (11%) 3/70 (4%) Amylase increased 12/101 (12%) 3/101 (3%) 13/70 (19%) 3/70 (4%) Hypomagnesemia 69/849 (8%) 27/849 (3%)* 72/853 (8%) 25/853 (3%)* Hypokalemia 11/55 (20%) 4/55 (7%)* 12/683 (2%) 4/683 (1%)* Renal / urinary Proteinuria 141/706 (20%) 13/726 (2%)* 142/675 (21%) 23/675 (3%)* Urinary tract infection 159/950 (17%) 17/950 (2%)* 146/923 (16%) 8/923 (1%)* Cardiovascular / vascular Hypertension 349/1231 (28%) 171/1251 (14%)* 379/1209 (31%) 169/1209 (14%)* Pulmonary embolism 75/679 (11%) 53/679 (8%)* 63/683 (9%) 48/683 (7%)* Respiratory Dyspnea 241/1261 (19%) 105/1281 (8%)* 209/1209 (17%) 93/1209 (8%)* Cough 35/289 (12%) 0/289 (0%)* 26/240 (11%) 0/240 (0%)* Pneumonitis / ILD 3/299 (<1%) 2/319 (<1%)* 0/286 (0%) 0/286 (0%) Neurological Headache 194/913 (21%) 3/913 (0%)* 215/884 (24%) 4/884 (0%)* Peripheral sensory neuropathy 291/941 (31%) 25/941 (3%)* 282/930 (30%) 25/930 (3%)* Dysgeusia 23/207 (11%) 0/207 (0%)* 23/209 (11%) 0/209 (0%)* Musculoskeletal Arthralgia 315/943 (33%) 3/943 (0%)* 304/884 (34%) 10/884 (1%)* Myalgia 154/724 (21%) 5/724 (1%)* 168/675 (25%) 3/675 (0%)* Back pain 40/271 (15%) 1/271 (0%)* 31/240 (13%) 3/240 (1%)* Dermatologic Rash 206/886 (23%) 22/906 (2%)* 136/892 (15%) 5/892 (1%)* Rash maculopapular 62/709 (9%) 21/709 (3%)* 18/683 (3%) 2/683 (0%)* Pruritus 126/879 (14%) 5/879 (1%)* 75/853 (9%) 0/853 (0%)* Alopecia 401/849 (47%) 0/849 (0%)* 434/853 (51%) 0/853 (0%)* Palmar-plantar erythrodysesthesia 23/207 (11%) 2/207 (1%)* 14/209 (7%) 0/209 (0%)* Endocrine / immune-related Hypothyroidism 85/697 (12%) 0/289 (0%)* 21/441 (5%) 0/240 (0%)* Hyperthyroidism 4/18 (22%) 0/18 (0%)* — — Immune-mediated / autoimmune (composite) 206/753 (27%) 37/345 (11%) 101/487 (21%) 17/286 (6%) Immune-related hepatitis 36/313 (12%) 9/313 (3%)* 28/286 (10%) 7/286 (2%) Infections Infection (any) 71/923 (8%) 15/923 (2%)* 76/930 (8%) 14/930 (2%)* Pneumonia 18/642 (3%) 6/642 (1%)* 12/644 (2%) 4/644 (1%)* Sepsis 3/642 (<1%) 3/662 (<1%)* 11/644 (2%) 5/644 (1%)* * Grade ≥3 value pools one or more studies that reported Grade 3/4 rather than Grade ≥3 (IMagyn050, González-Martín, Moroney; Gaillard reported Grade 3 and Grade 4 separately, summed here). Grade 5 events, where applicable, were tabulated separately in those studies and are not included. Abbreviations: ILD, interstitial lung disease; WBC, white blood cell; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GI, gastrointestinal. Neutrophil / platelet / lymphocyte / WBC “count decreased” terms are pooled with neutropenia / thrombocytopenia / lymphopenia / leukopenia respectively. Pooled safety outcomes Any-grade AEs were near-universal in both arms and did not differ, with a pooled RR of 1.00 (95% CI 1.00 to 1.00; three comparisons) and no heterogeneity (I² = 0.0%, Q p = 0.95). Serious adverse events were more frequent with atezolizumab, with a pooled RR of 1.32 (95% CI 1.05 to 1.67, p = 0.036; three comparisons) and low heterogeneity (I² = 32.4%, Q p = 0.27). Immune-related adverse events of any grade were increased (RR 1.57, 95% CI 1.12 to 2.20, p = 0.024; four comparisons), with moderate heterogeneity in the magnitude of effect (I² = 54.0%, Q p = 0.09) and a stable estimate on leave-one-out analysis (1.42 to 1.75). Grade ≥3 irAEs were approximately doubled (RR 2.23, 95% CI 1.05 to 4.74, p = 0.044; three comparisons), with moderate heterogeneity (I² = 42.8%, Q p = 0.18); the wide interval reflects the small number of events (Figure 5). Pooled single-arm incidence of key safety events in the atezolizumab arm ranged from 1.8% (95% CI 1.1 to 2.9) for grade 5 or treatment-related deaths to 66.5% (95% CI 53.0 to 77.8) for grade ≥3 AEs, with several outcomes showing substantial between-trial heterogeneity (Table 5). Table 5. Pooled Safety Outcomes of Atezolizumab in Ovarian Cancer. Safety outcome Studies, k (arms) Events / total Primary GLMM, % (95% CI) Leave-one-out range, % I², % 95% prediction interval, % Grade ≥3 AE 10 (11) 1312 / 1699 66.5 (53.0–77.8) 62.0–68.8 93.7 21.4–93.6 TRAE, grade ≥3 8 (8) 851 / 1625 39.5 (22.2–59.8) 34.2–46.1 97.7 3.4–92.3 Serious AE (SAE) 6 (6) 572 / 1180 38.5 (24.8–54.3) 34.4–45.6 93.9 7.2–83.4 AE-related discontinuation 9 (10) 295 / 1473 11.6 (6.6–19.7) 10.0–14.5 89.6 1.9–47.5 Grade 5 / treatment-related death 12 (14) 33 / 1738 1.8 (1.1–2.9) 1.4–1.9 18.4 0.7–4.2 Abbreviations: AE, adverse event; CI, confidence interval; GLMM, generalized linear mixed model; SAE, serious adverse event; TRAE, treatment-related adverse event. Risk of bias and certainty of evidence The five randomized trials contributing comparative data were appraised with RoB 2. Four were rated overall low risk and one some concerns, driven by its open-label design and investigator-assessed outcome. The seven data sets analyzed as single arms (the five single-arm trials and the two randomized trials that contributed single-arm data only) were assessed with MINORS, scoring 11 to 13 of 16, with deductions concentrated on consecutive inclusion, independent endpoint assessment, loss to follow-up, and prospective sample-size calculation (Figure 6). Certainty of evidence was assessed across 14 outcomes. Of the nine comparative outcomes from randomized controlled trials, five were rated high certainty, three moderate, and one very low. Downgrading was driven solely by inconsistency and imprecision; risk of bias, and indirectness raised no concerns. The five single-arm pooled proportions began at low certainty and, except treatment-related death, were downgraded to very low for inconsistency, and two of these were downgraded for imprecision as well (Table 6). Table 6. Summary of Findings with GRADE Domain Assessments. Certainty assessment № patients(intervention / comparator) Effect(95% CI) Certainty(GRADE) Impor-tance Outcome No studies Studydesign / Starting certainty Analysis model Risk ofbias Incon-sistency Indirect-ness Impre-cision Other consi-derations Progression-free survival 5 RCT / High IV random-effects(REML, Knapp–Hartung) not serious not serious not serious not serious none 1,562 / 1,364 HR 0.88 (0.83–0.93) ⨁⨁⨁⨁High Critical Progression-free survival(PD-L1-positive) 4 RCTHigh IV random-effects(REML, Knapp–Hartung) not serious not serious not serious not serious none 686 / 611 HR 0.82 (0.76–0.89) ⨁⨁⨁⨁High Critical Overall survival 4 RCT / High IV random-effects(REML, Knapp–Hartung) not serious not serious not serious not serious none 1,355 / 1,155 HR 0.86 (0.78–0.96) ⨁⨁⨁⨁High Critical Overall survival(PD-L1-positive) 3 RCTHigh IV random-effects(REML, Knapp–Hartung) not serious not serious not serious serious none 610 / 538 HR 0.83 (0.71–0.98) ⨁⨁⨁◯Moderate Critical Comparative efficacy — response (risk ratio) Objective response rate 5 RCT / High IV random-effects(REML, Knapp–Hartung) not serious very serious not serious serious none 1,155 / 933 RR 0.88 (0.52–1.49) ⨁◯◯◯Very Low Important Comparative safety (risk ratios) Any-grade adverse event 3 RCT / High IV random-effects(REML, Knapp–Hartung) not serious not serious not serious not serious none 1,130 / 1,139 RR 1.00 (1.00–1.00) ⨁⨁⨁⨁High Important Serious adverse event (vs comparator) 3 RCT / High IV random-effects(REML, Knapp–Hartung) not serious not serious not serious not serious none 1,130 / 1,139 RR 1.32 (1.05–1.67) ⨁⨁⨁⨁High Critical Immune-related AE, any grade 4 RCT / High IV random-effects(REML, Knapp–Hartung) not serious serious not serious not serious none 1,538 / 1,340 RR 1.57 (1.12–2.20) ⨁⨁⨁◯Moderate Important Immune-related AE, grade ≥3 3 RCT / High IV random-effects(REML, Knapp–Hartung) not serious not serious not serious serious none 1,331 / 1,131 RR 2.23 (1.05–4.74) ⨁⨁⨁◯Moderate Critical Single-arm safety — pooled proportions of the atezolizumab arm Grade ≥3 AE (pooled proportion) 10 Single-arm / Low Binomial GLMM not serious Serious not serious not serious none 1,699 / – 66.5% (53.0–77.8) ⨁◯◯◯Very Low Important Treatment-related AE, grade ≥3 (pooled proportion) 8 Single-arm / Low Binomial GLMM not serious very serious not serious Serious none 1,625 / – 39.5% (22.2–59.8) ⨁◯◯◯Very Low Important Serious AE (pooled proportion) 6 Single-arm / Low Binomial GLMM not serious very serious not serious not serious none 1,180 / – 38.5% (24.8–54.3) ⨁◯◯◯Very Low Critical AE-related treatment discontinuation (pooled proportion) 9 Single-arm / Low Binomial GLMM not serious very serious not serious Serious none 1,473 / – 11.6% (6.6–19.7) ⨁◯◯◯Very Low Important Grade 5 / treatment-related death (pooled proportion) 12 Single-arm / Low Binomial GLMM not serious not serious not serious not serious none 1,738 / – 1.8% (1.1–2.9) ⨁⨁◯◯Low Critical Certainty (GRADE): ⨁⨁⨁⨁ High · ⨁⨁⨁◯ Moderate · ⨁⨁◯◯ Low · ⨁◯◯◯ Very Low.  Each domain is rated not serious / serious (−1) / very serious (−2). RCT outcomes start High; single-arm pooled proportions start Low. Abbreviations: AE, adverse event; CI, confidence interval; GLMM, generalized linear mixed model; GRADE, Grading of Recommendations Assessment, Development and Evaluation; HR, hazard ratio; IV, inverse variance; PD-L1, programmed death-ligand 1; RCT, randomized controlled trial; REML, restricted maximum likelihood; RR, risk ratio Discussion Standard first-line management of OC pairs primary debulking surgery with paclitaxel and carboplatin, reserving neoadjuvant chemotherapy and interval debulking for patients unfit for upfront resection [4]. Maintenance bevacizumab and PARP inhibitors followed, though their benefit concentrates in BRCA1/2-mutated and homologous recombination-deficient tumors [10]. PD-1/PD-L1 inhibitors occupy a biomarker-selected niche in mismatch repair-deficient, microsatellite instability-high, or high tumor mutational burden disease [2]. Atezolizumab is given with bevacizumab or chemotherapy rather than alone, since monotherapy produces limited activity in this immunologically cold tumor, where low mutational burden and abundant regulatory T cells and tumor-associated macrophages constrain T-cell responses [3]. This carries appreciable toxicity, with treatment-related events in roughly 71% of patients and irAE in 29% in recurrent disease [2], dominated by grade 1-2 thyroid dysfunction, fatigue, nausea, and fever [11], and all-grade hypertension near 31% when bevacizumab is added [7]. The present meta-analysis found that atezolizumab lowered 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), each with zero heterogeneity. The individual phase III trials (IMagyn050, ATALANTE) were sized for larger effects, so their concordant sub-threshold estimates missed significance alone; pooling resolves a survival benefit no single trial could establish. Class-level reviews returned overall nulls because they combined pharmacologically distinct antibodies and mixed monotherapy with combination regimens. Vida et al. pooled ten randomized trials and found no overall effect (PFS HR 0.98, 95% CI 0.85 to 1.12; I² = 67%) [10], and Ahmadi et al. reported survival intervals crossing unity (PFS HR 0.82; OS HR 0.85) [3]. Ahmadi's network meta-analysis nonetheless ranked checkpoint inhibitor plus chemotherapy combinations among the highest for survival [3]. The current analysis extends that class-level signal to atezolizumab specifically, converting a ranking of mixed agents into a homogeneous, significant estimate for a single antibody given on a chemotherapy or bevacizumab backbone. Expression of PD-L1 has been proposed as a predictive biomarker for checkpoint blockade in ovarian cancer. The evidence regarding this matter is mixed: one meta-analysis reported a significant PFS benefit with PD-1/PD-L1 inhibitors plus chemotherapy in PD-L1-positive patients (HR 0.65, 95% CI 0.46-0.92) [3], while a separate pooled analysis of ten randomized trials across multiple anti-PD-1 and anti-PD-L1 agents found no significant PFS benefit in this subgroup (HR 0.91, 95% CI 0.79-1.04, I² = 64.2%) [10]. That pooled analysis attributed its null result largely to inconsistent PD-L1 thresholds and scoring platforms across the included trials, most of which relied on an arbitrary 1% cutoff without assay harmonization. The problem went beyond the cutoff value itself; an exploratory 5% PD-L1 threshold suggested possible benefit in IMagyn050 (HR=0.64, 95% CI 0.43-0.96) [4], but this signal was not replicated in the FIRST trial despite using the same 5% cutoff, because the two trials scored PD-L1 differently (tumor area proportion versus immune cell score) [10]. The PD-L1-positive findings in the current analysis (PFS HR 0.82, 95% CI 0.76-0.89; OS HR 0.83, 95% CI 0.71-0.98), both without heterogeneity, are more in line with a differential benefit in PD-L1-positive patients than with the null pooled estimate described above. This remains hypothesis-generating, as no formal interaction testing was performed, and confirmation would require standardized PD-L1 assays. The survival benefit did not extend to ORR in this review, which showed no difference between arms (RR 0.88, 95% CI 0.52 to 1.49). This dissociation may reflect checkpoint blockade acting on the durability of disease control rather than tumor shrinkage, consistent with the modest single-agent activity reported in prior studies, where pooled monotherapy ORR was only 6.7% versus 36% and 30% for combinations with chemotherapy and anti-angiogenic agents, respectively [2]. Prior studies also report that response varies by treatment line and platinum status: ORR was as low as 11.6% in heavily pretreated recurrent disease, and as high as 44% with select combination regimens in platinum-resistant patients [1,3]. This variability likely contributes to the heterogeneity in the pooled ORR estimate (I² = 92.3%). This review demonstrated identical any-grade AEs between arms (RR 1.00), but atezolizumab raised SAEs (RR 1.32, 95% CI 1.05 to 1.67), any-grade irAE (RR 1.57, 95% CI 1.12 to 2.20), and grade ≥3 irAE (RR 2.23, 95% CI 1.05 to 4.74). The excess is immune-mediated and consistent with a meta-analysis of atezolizumab plus bevacizumab that reported 14.1% grade 3 hypertension [7]. A modest survival gain comes at roughly double the risk of a high-grade immune event. Grade ≥3 rates are lower for less intensive regimens, at 32% for single-arm pembrolizumab [11], 15% in endometrial cancer [26], and 5.4% for tarlatamab in small-cell lung cancer [8]. Against that range, the atezolizumab arm in the present analysis reached 66.5% for grade ≥3 AEs, with 38.5% for SAEs, 11.6% for treatment discontinuation, and 1.8% for treatment-related death. That ordering places the excess with the chemotherapy and bevacizumab backbone rather than the antibody. Fatal toxicity stayed below 2%, and discontinuation near 12% marks the practical limit on tolerability. Unlike prior reviews, which appraised study quality but did not grade the certainty of their pooled estimates [1,11], the present analysis paired GRADE with RoB 2 and MINORS assessment, allowing the survival benefit to be reported with an explicit certainty rating Our meta-analysis has several limitations. First, the survival estimates mainly rest on combination trials, so atezolizumab cannot be separated from its backbone. Second, a few large phase III trials dominate the pooled result, so the low heterogeneity may reflect their weight rather than broad replication. Third, OS was immature in several trials and may attenuate with longer follow-up. Finally, enrollment was largely restricted to good performance status (ECOG 0 to 1, 97.4%), limiting generalizability to frail patients common in recurrent disease. Conclusion Adding atezolizumab to a chemotherapy or bevacizumab backbone in stage 3 and 4 ovarian cancer was associated with a small survival benefit, driven by delayed progression rather than tumor regression, at the cost of increased immune-related toxicity. As the effect was modest and inseparable from its backbone, current evidence may not support routine use. Declaration Conflicts of interest: The authors have no conflicts of interest to disclose. Ethical approval: Not applicable, as systematic reviews do not require ethical approval. Patient consent (participation and publication): Not applicable. Funding: The present review received no financial support. Acknowledgments: None to be declared. Authors' contributions: R.H.A. was responsible for conceptualization, methodology, and validation. S.S.O. contributed to validation and writing – review & editing. S.M.A. provided supervision and contributed to methodology. S.H.M. and K.K.M. performed investigations and contributed to writing – review & editing. M.Q.M. and Y.M.M. contributed resources and assisted with writing – review & editing. S.H.K. contributed to data curation and writing – review & editing. H.A.N. handled data curation, validation, and writing – review & editing. A.G.H. contributed to validation and writing – review & editing. Z.T.H. wrote the original draft, conducted formal analysis, performed investigations, contributed to methodology, and performed visualization. D.D.M. contributed to writing the original draft and formal analysis. M.J.M., S.S.R., and F.M.Q. contributed to writing – review & editing. B.A.A. wrote the original draft and contributed to methodology. All authors read and approved the final manuscript. Use of AI: During the preparation of this work, the authors used Claude Opus 4.8 (Anthropic) to assist with text drafting and language editing, code development in R, and figure generation. After using this tool, the authors reviewed and edited the content as necessary and take full responsibility for the content of the publication. Data availability statement: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.