Introduction: progression of advanced epithelial ovarian cancer (EOC) on olaparib may diminish the efficacy of subsequent chemotherapy in recurrent disease setting. However, the impact of progression of EOC during maintenance therapy with olaparib after frontline therapy has not been well studied.Materials and methods: this retrospective study enrolled patients of BRCA / HRD + FIGO stage III–IV EOC with confirmed progressive disease after frontline treatment treated since 2014 until 2022 who either received (arm A) or not (arm B) olaparib as maintenance therapy. To ensure the balance of the compared groups during the study propensity score matching analysis was conducted (cardinality method using MatchIT package in R) with 1:1 ratio of patients in trial arms. The groups were balanced according to the presence of residual tumor after initial treatment, the duration of platinum-free interval after the frontline therapy, secondary local therapy for recurrent disease, treatment with platinum drugs for relapse and subsequent bevacizumab. The primary endpoint of the study was progression-free survival (PFS).Results: the initial population consisted of 259 patients, after the matching procedure 76 patients were enrolled in the study. The median age of patients was 48 years in the arm A and 50 years in the arm B (p = 0.989), 12 (32 %) had FIGO stage IV in both arms (p = 1.000), 25 (66 %) patients in both arms had platinum-free interval ≥ 12 months. With a median follow-up of 42.8 mo. (0.6–70.1 months) median PFS was 6.9 (95 % CI 6.2–10.6 months) and 12.2 (95 % CI 9. 6–21.3 months) in arm A and B, respectively (hazard ratio [HR] 2.89; 95 % CI 1.63–5.12; p < 0.001). Median overall survival was 23.2 months. and 68.2 mo., respectively (HR 4.15; 95 % CI 1.62–10.6).Conclusion: efficacy of subsequent chemotherapy is apparently reduced following progression of BRCA / HRD + EOC on maintenance olaparib therapy in frontline setting. Further trials should assess optimal approaches for these patients.

Primary cardiac osteosarcoma is an extremely rare malignant tumor, its incidence is less than 10 % of all primary cardiac sarcomas. Currently, less than 100 cases of this disease have been reported, and there is no consensus on the optimal approaches to treatment. The article presents a clinical case of primary cardiac osteosarcoma noting the effectiveness of two chemotherapy lines and describes difficulties in tumor morphology interpretation.

The TC combination regimen (paclitaxel + carboplatin) is the “gold standard” first-line therapy for disseminated endometrial cancer (EC). The use of hormone therapy (HT) in the first-line setting is limited. Until recently, patients with disseminated EC had unfavorable outcomes despite the standard-of-care treatment (chemotherapy (CHT) and HT). None of the available cytostatics could improve disease control and survival in patients who have received standard platinum-based therapy. Evidently, the poor treatment outcomes of disseminated EC suggested that therapeutic approaches should be changed, and more effective treatment regimens should be developed. The treatment of disseminated EC has been revolutionized with deeper understanding of carcinogenesis, a new molecular classification of EC, and stratification of treatment approaches according to the biological potential of the tumor. The most significant advances included understanding the role of microsatellite instability (MSI) and DNA mismatch repair (MMR) deficiencies as a predictor of high efficacy of immunotherapy, a novel class of systemic therapies for disseminated EC. This review article focuses on the evolution of systemic therapy for disseminated EC. Here we discuss in detail the results of key international trials of HT, first and second lines of chemotherapy, targeted therapy, immunotherapy, and immunotherapeutic/ targeted agents for disseminated EC. Biological markers, such as MSI and PD-L1, their correlation with the response rate, and the mechanism of synergy between pembrolizumab and lenvatinib are discussed in detail.

Background: overall survival (OS) is the gold-standard primary end point for cancer clinical trials to evaluate the outcome of therapy. However, in some cases the direct assessment of OS can be inappropriate. Therefore, various surrogate endpoints, such as overall response rate (ORR) and progression-free survival (PFS), are used commonly in clinical trials. Aim: to assess the relevance of mentioned endpoints in platinum-resistant recurrent ovarian cancer. Patients and Methods: we used PubMed queries to search for all ovarian cancer studies from 01/01/2000 to 07/01/2019. Key inclusion criteria were: 1) recurrent epithelial ovarian cancer, 2) platinum-free interval ≤6 months, 3) standard chemotherapy (CT) without targeted and/or experimental drugs, 4) reported objective response rate, PFS and OS, as well as response assessment criteria. Correlation and linear regression analysis were conducted to identify the relationship between various markers of therapy efficacy. Trials were weighted according to the number of enrolled patients. Statistical analysis of the data was performed using R and RStudio software. Results: 7156 studies were reviewed, and 157 studies meeting the inclusion/exclusion criteria were selected. PFS and OS data were available in 104 (n=5081) and 99 (n=5089) studies, respectively. The average ORR was 17.2% (non-platinum CT — 13.6%, platinum-based CT — 36.7%; p<0.001), and median PFS was 3.68 months (3.38 and 5.37 months, respectively; p<0.001). A significant correlation was found between ORR and PFS (r=0.62; p<0.001). Linear regression analysis identified 0.5 months increase in median PFS for every 10% increase in ORR (p<0.001). There was no significant correlation between ORR and OS. Conclusions: the meta-analysis results provide valuable information for understanding the role of surrogate biomarkers in platinum-resistant recurrent ovarian cancer. ORR is a reliable predictor of PFS in this patient population. KEYWORDS: ovarian cancer, platinum resistance, chemotherapy, surrogate endpoints, systematic review, meta-analysis. FOR CITATION: Rumyantsev A.A., Tyulyandina A.S., Israelyan E.R. et al. Surrogate endpoints in platinum-resistant recurrent ovarian cancer. Russian Medical Inquiry. 2022;6(6):319–325 (in Russ.). DOI: 10.32364/2587-6821-2022-6-6-319-325

Tyrosine kinase inhibitors of the first, second and third generations are the main treatment method for non-small cell lung cancer with EGFR mutation. About 60% of patients progressing on a first-generation or second-generation tyrosine kinase inhibitor acquire T790M mutation. An alternative is first-line osimertinib, but second-line treatment options are limited, and therefore it is important to find a strategy that allows to extend the effective treatment of TKI. One of the rational approaches is the use of a combination of a first-generation tyrosine kinase inhibitor with anti-VEGF agents. The available information sources show an increase in the effectiveness of the combined use of erlotinib and antiangiogenic drugs-bevacizumab and ramucirumab. The combination of erlotinib and bevacizumab in several studies of the second — third phase, led to a statistically significant increase in progression-free survival, but did not show a significant increase in overall survival. In the Phase 3 RELAY study, the combination of erlotinib and ramucirumab showed comparable efficacy with the third-generation TKI — osimertinib in the first line, however, overall survival results are not yet available. At the same time, there are more opportunities to choose the secondline mode, taking into account the known frequency of detection of the T790M mutation. The optimal treatment sequence is discussed, with the option of prescribing a combination of erlotinib with bevacizumab or ramucirumab in the first line and osimertinib in the second in the presence of the T790M mutation. In such patients, osimertinib may be prescribed in the second line.

Background. The search and use of new molecular prognostic and predictive markers of efficacy detected by liquid biopsy are aimed at understanding the biology of Carcinomas of Unknown Primary (CUP) and improving results of patient treatment. The review is devoted to advances in scientific and clinical research on this issue.Materials and methods. In order to assess the current state of the problem, a search and analysis of relevant data of the scientific databases PubMed, Medline, RISC was carried out.Results. The scientific rationale for the use of liquid biopsy in clinical practice to improve the treatment of cancer patients with CUP is presented. The results of the use of modern approaches to the analysis of fluid biopsy samples in CUP are presented. In particular, the features of using circulating free DNA, circulating tumor DNA, circulating tumor cells in the analysis are considered. The modern possibilities of determining tissue specificity using liquid biopsy in CUP are discussed. The prospects for the development of liquid biopsy for improving diagnostics, determining the prognosis of the disease, and choosing a strategy for treating CUP and the treatment monitoring have been determined.Conclusion. A review of the literature confirms that modern methods of molecular profiling of tumor cells obtained both as a result of liquid biopsy and tissue biopsies will make a significant contribution to the determination of tissue specificity, molecular characteristics of CUP for a personalized approach in order to improve strategies and treatment outcomes for patients with CUP.

In most cases triple negative breast cancer is characterized by an aggressive course of disease and early development of resistance to chemotherapy. Thereafter, the late-line treatment choice, usually after anthracyclines and taxanes, is problematic due to the limited amount of effective and low-toxic cytostatics. In our opinion, in this situation the use of eribulin which possesses unique antitumor action mechanisms is a good option. An illustrative case of a pronounced antitumor effect of eribulin in metastatic breast cancer with triple negative phenotype resistant to previous lines of chemotherapy is presented.

Liver metastases of gastric cancer determine the poor prognosis. Until now The expediency of their surgical removal has been controversial. However, according to a number of studies, the removal of potentially operable isolated liver metastases allows a significant increase of overall and relapse-free survival in some cases. The review is dedicated to the analysis of prognostic factors that allow selecting patients for surgical removal of liver metastases of gastric cancer. The main criteria are: effective perioperative chemotherapy; stage under T4, N0, absence of lymphovascular invasion, absence of peritoneal dissemination, number less than 3, size up to 4 cm, localization of metastases in one lobe, low level of cancer markers CA 19-9 and CEA.

This is a description of a case of extremely rare pathology, a primary mucinous adenocarcinoma of renal pelvis. The survey data, including CT-scan, as well as the results of histological, immunohistochemical and molecular genetic studies are presented. The disease progressed after surgical treatment; chemotherapy regimens and their effectiveness are given.

Genetic factors, immune dysfunction, chronic inflammation, and dysbiosis of the intestinal microbiome (IM) are believed to participate in the pathogenesis of colorectal cancer (CRC). The positive role of IM regulation in the treatment of inflammatory bowel disorders is determined by a reduction in the growth of pathogenic bacteria and an increase in the production of anti-inflammatory factors. Currently, the available data suggests that the IM dysregulates the immune response against the tumor in its microenvironment, thus either slowing down or accelerating the efficacy of antitumor therapy. Clinical studies have reported benefits of CRC therapy selected based on IM in improving immune intestinal homeostasis, epithelial barrier functions, and quality of life. Moreover, the specific IM signature may modulate the sensitivity to chemoand/ or radiotherapy, as well as the prognosis in patients with colorectal cancer. In this article, we presented the general challenges of the CRC therapy based on IM data in combination with immunotherapy, and described the future prospects of this approach.

Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase domain, which has shown effectiveness in the treatment of non-small cell lung cancer with activating EGFR mutation. A number of large randomized studies have shown a significant increase in survival without progression in the use of erlotinib and other tyrosine kinase inhibitors in comparison with standard chemotherapy. At the same time, there were no differences in the overall survival rate, which is due to the high frequency of tyrosine kinase inhibitors use in subsequent therapy lines in patients who had progression during the first-line chemotherapy. At the same time, this retrospective study showed an obvious (more than doubling) increase in the overall survival rate of patients receiving treatment with tyrosine kinase inhibitors as compared to historical control. There were no significant differences between the first and second generation tyrosine kinase inhibitors. Mutation of T790M is one of the main mechanisms of resistance to erlotinib. When progressing against the background of erlotinib treatment, the third generation tyrosine kinase inhibitor osimertinib is effective in case of T790M mutation detection. The combination of erlotinib with bevacizumab leads to an increase in survival without progression, without affecting the overall survival rate. The combined use of chemotherapy and tyrosine kinase inhibitors requires further study. An example of a long-term effect on the background of erlotinib treatment in a patient with non-small-cell lung cancer of stage IV with EGFR mutation is given. The total duration of treatment was 68 months, including the therapy with erlotinib in combination with bevacizumab and local radiation therapy on the progression zone (rib metastasis), which lasted for 21 months against the background of the indolent course of the disease.

Radiation therapy (RT) plays an important role in treatment of primary and metastatic CNS tumors and some non-neopiastic conditions (arteriovenous malformations, trigeminal neuralgia). Radiation necrosis (RN) is a common adverse effect of RT. Until recently steroid therapy was used as a main treatment regimen for RN. Mechanisms of RN development are not clear; however, it was shown that vascular endothelial growth factor (VEGF) plays a critical role in its formation. A number of surveys showed efficacy of bevacizumab as an anti-VEGF agent in treatment of RN. Radiation necrosis pathogenesis, diagnostics and treatment are summarized in this review.

Anemia is a common hematological complication in cancer patients receiving chemotherapy. Reduction of hemoglobin level is accompanied by a significant deterioration in the patients’ life quality. A transfusion of erythrocyte mass is used to rapidly increase the hemoglobin level in case of development of a symptomatic anemia. However, a large range of risks limit the wide use of blood transfusions. Erythropoiesis-stimulating proteins are the drugs that reduce the need for blood transfusions. Treatment with erythropoietins provides a smooth and prolonged rise in the hemoglobin level, the release of fully functional red blood cells into the blood. The use of erythropoietins can significantly improve the quality of life of cancer patients without reducing the effectiveness of chemotherapy.

No standard of care has been established for patients with progressive glioblastoma (rGB). Previous studies suggested that bevacizumab (BEV) is safe and produces responses that result in a decreased use of glucocorticoids and increased progression-free survival (PFS) with an unclear effect on overall survival (OS). Crossover to BEV in the control arm is the possible reason why the advantage of BEV has not been proven in Phase III trials. We present our own retrospective data on the effectiveness of the use of BEV in the rGB. Special attention was paid to the analysis of the consequences of BEV discontinuation in the absence of tumor progression and the benefit of continuing or resuming BEV at relapse.

Basing on new clinical trials data, the optimal duration of colon cancer adjuvant therapy is considered depending on molecular characteristics and pathologic tumor staging. The presented results potentially influence the clinical decision on chemotherapy regimen choice and optimal duration of adjuvant treatment.

The article presents the results of the meeting of the Advisory board “Modern treatment approaches for advanced renal cell carcinoma”, held on Apr 24, 2017, with the aim to discuss current approaches to inoperable, locally advanced and advanced renal cell carcinoma. To discuss the Russian experience with lenvatinib in the routine clinical practice and get the experts’ opinion on the perspectives directions of lenvatinib study in renal cell carcinoma landscape.

First generation EGFR inhibitors have significantly improved the outcomes of drug treatment of patients with metastatic NSCLC, as well as notably increased the frequency of achieving objective response and time to progression of the disease. Today, the arsenal of efficient drugs is enlarged by the introduction into clinical practice of the second-generation EGFR inhibitor - afatinib. According to clinical studies, its full therapeutic effect is determined not only by the status of activating mutation but also its type. Afatinib also significantly increases the overall survival median in case of exon 19 EGFR mutation. This is an extremely important factor in the choice of adequate treatment. Afatinib is also effective in developing resistance to first-generation EGFR inhibitors and is an alternative to second-line therapy. It is hard to overestimate the benefits of the drug which allows for a meaningful delay in chemotherapy for such patients.

Introduction of toremifene into clinical practice significantly enhances the potential of current endocrine therapy for luminal subtypes of breast cancer. Toremifene demonstrates same or greater efficacy compare with tamoxifen but has a more favorable spectrum of side effects including thromboembolic complications. These benefits can significantly reduce the number of cases of irrational discontinuation of therapy. The possibility of safe use of high doses of toremifene including the preoperative therapy regimens which are now being studied also seems promising.