R.V. Orlova1, 2, Ya.R. Gorkina2
1Saint Petersburg State University, Saint Petersburg
2City Clinical Oncology Dispensary, Saint Petersburg
Orlova R.V. – MD, Professor of the Department of Oncology, Head of the Specialized Oncology Center, Chief oncologist
Northwest Regional Scientific and Clinical Center named after L.G. Sokolov
7–9 Universitetskaya Embankment, 199034, Saint Petersburg, Russian Federation, e-mail: orlova_rashida@mail.ru, ORCID ID: 0000-0002-0619-2205
Abstract. Cervical cancer (CC) ranks fifth in incidence among women in Russia. Despite progress in treatment, mortality rates continue to rise, especially among young and middle-aged women. Traditional therapies, such as surgery and chemoradiation therapy, demonstrate effectiveness in local forms of the disease, but in metastatic and recurrent CC, the five-year survival rate does not exceed 15%. The introduction of checkpoint inhibitors immunotherapy (ICI), such as pembrolizumab, has opened up new opportunities for the treatment of this category of patients.
Objective – to analyze the current data on predictive factors affecting the ICT effectiveness in breast cancer, including biomarkers (PD-L1, HPV, TMB, MSI, TILs, cDNA, NLI) and clinical characteristics (histological subtype, ECOG status).
Material and methods. A systematic review of 2019–2023 publications from PubMed, Scopus, eLibrary databases and clinical recommendations (Russian Ministry of Health, ESMO, NCCN) was conducted. Inclusion criteria: research on ICT in breast cancer, data on biomarkers and clinical outcomes. We analyzed 18 relevant studies, including KEYNOTE 158 and CheckMate 648.
Results. We found that PD-L1 expression (CPS ≥ 1) correlates with objective response (OR) by up to 28.9%, but its predictive value is limited. HPV-positive tumors express PD-L1 more often (65% vs. 35%, p = 0.03) and demonstrate better survival (18 vs. 10 months). High TMB (>10 mutations/Mb) and MSI-H status (1–3% of cases) are associated with HR 25–45%. A high TILs level (>10%) increases the survival rate to 34%. A 50% decrease in cDNA after 4 weeks predicts an increase in survival from 9 to 16 months (p = 0.03). ECOG 0 is associated with HR (25 vs. 8%) with ECOG ≥1 (p = 0.005).
Result. The integration of biomarkers and clinical factors allows optimizing therapy. However, unresolved issues remain, such as the standardization of thresholds for TMB and PD-L1, conflicting data on the role of HPV (Bonneville et al., 2023), and heterogeneity of biomarker assessment methods.
Conclusion. The most significant predictors are PD-L1+, HPV status, and high TMB/TILs. The combination of biomarkers increases the prognosis accuracy (for example, PD-L1 + TMB >10 → HR 34%). Promising areas: dynamic monitoring of cDNA, study of the microbiome, development of personalized algorithms.
Key words: cervical cancer, checkpoint inhibitors, immunotherapy, pembrolizumab, biomarkers, prognostic factors, clinical trials.