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PD-L1 expression was more common in HRD-positive high-grade serous ovarian cancer, indicating potential prognostic value in newly diagnosed cases.
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In an ancillary analysis of the phase 3 PAOLA-1/ENGOT-ov25 trial (NCT02477644), PD-L1 expression assessed by combined positive score (CPS) and immune cell (IC) score was found to be significantly associated with homologous recombination deficiency (HRD) status and demonstrated prognostic relevance in patients with newly diagnosed, advanced high-grade serous ovarian cancer (HGSOC).
Findings presented at the 2025 ESMO Gynecological Cancers Congress showed that PD-L1 positivity was more frequently observed in patients with HRD-positive tumors vs those with HRD-negative tumors when using CPS and IC scoring methods. Specifically, 70.4% of HRD-positive population (n =189) had a PD-L1 CPS of at least 1 compared with 53% of patients with HRD-negative tumors (n = 101; P = .002). A similar trend was seen using IC scoring, with 65.1% of HRD-positive tumors vs 52% of HRD-negative tumors meeting the CPS of at least 1 threshold (P = .012). These associations were statistically significant.
Notably, in the overall population, the rates of PD-L1–positive tumors using CPS, IC, and tumor proportion score (TPS) were 66.1%, 62.4%, and 38.2%.
A univariate multivariate Cox regression analyses demonstrated that PD-L1 positivity by CPS (HR, 0.62; 95% CI, 0.45-0.86; P = .005) and IC score (HR, 0.60; 95% CI, 0.43-0.83; P = .002) was independently associated with improved overall survival (OS). A multivariate analysis also showed improved OS in PD-L1–positive patients based on CPS (HR, 0.70; 95% CI, 0.50-0.97; P = .037) and IC score (HR, 0.68; 95% CI, 0.49-0.95; P = .025).
“PD-L1 positivity assessed by CPS is associated with [increased] HRD-positive status and better OS, independent of age, surgery timing, treatment arm, residual disease, FIGO stage, or HRD status,” lead study author Isabelle Treilleux, MD, of the Department of Biopathology at Centre Léon Bérard in Lyon, France, said in a presentation of the data. “A [positive] trend [was] observed for PFS, although not statistically significant. [These findings] from a subgroup study…from PAOLA-1 requires additional studies.”
In May 2020, based on prior data from PAOLA-1, the FDA approved the combination of olaparib (Lynparza) and bevacizumab (Avastin) for first-line maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with HRD-positive status, defined by either a deleterious or suspected deleterious BRCA mutation and/or genomic instability.2
This ancillary analysis of the PAOLA-1 was a retrospective, biomarker-focused investigation assessing the prognostic value of PD-L1 expression and its correlation with HRD status— along with the prognostic value of both biomarkers—in patients with newly diagnosed, high-grade serous ovarian carcinoma.1
PAOLA-1 was a global, randomized study evaluating the efficacy of maintenance olaparib plus bevacizumab vs placebo plus bevacizumab following a response to first-line platinum-based chemotherapy. To conduct the ancillary analysis, investigators selected 324 patients from the PAOLA-1 population (n = 806), based on tumor specimens with the highest tumor area and content. All patients had FIGO stage III or IV high-grade serous ovarian cancer.
Tumor samples were evaluated for HRD status using the Myriad MyChoice® CDx HRD assay, which defines HRD positivity as the presence of a BRCA mutation and/or high genomic instability score.
PD-L1 expression was assessed using the PD-L1 Immunohistochemistry (IHC) 22C3 pharmDx assay, an FDA-approved companion diagnostic. PD-L1 scoring was conducted using three predefined methods: TPS, IC score, and CPS, and cutoff values for positivity were based on recommendations for PD-L1 testing in other organs. All slides were independently reviewed by 7 experienced pathologists trained in PD-L1 scoring.
The primary objective of the analysis was to evaluate the association between PD-L1 expression and HRD status, as well as their potential prognostic value in the context of maintenance treatment with olaparib and bevacizumab. Key end points included the distribution of PD-L1 expression across HRD-defined subgroups and the correlation of biomarker-defined subsets with clinical outcomes such as PFS and OS.
In the 324 patients evaluated for this analysis, the mean age was 59.3 years. The majority of patients had a primary tumor in the ovary (87.3%), had FIGO stage IIIC disease (67.9%), and did not have metastases (75.9%). Patients either underwent primary debulking with macroscopic resection (34.3%); primary debulking without macroscopic resection (25.3%); interval debulking with macroscopic resection (25.6%), interval debulking without macroscopic resection (10.2%); or no surgery (4.6%).
HRD positivity was reported in 58.4% of patients, including 60.6% of patients in the olaparib arm (n = 216) and 53.7% in the placebo arm (n = 108). Notably, HRD status was unknown in 10.5% of patients (n = 34) in the ancillary analysis population, and they were excluded from the correlation analysis between PD-L1 and HRD.
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