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Background: Prolgolimab is the first Russian PD-1 inhibitor approved for the first-line treatment of unresectable or metastatic melanoma and advanced non-small cell lung cancer. It was approved in two weight-based regimens of 1 mg/kg Q2W and 3 mg/kg Q3W, but because of re-evaluation of weight-based dosing paradigm, studying of a fixed-dose regimen was considered perspective., Methods: We conducted a multicenter, single-arm, open-label efficacy, pharmacokinetics, and safety study to obtain data that would allow the approval of the new flat dosing regimen of prolgolimab in patients with previously untreated unresectable or metastatic melanoma (BCD-100-8/FLAT, NCT05783882). The primary objective was to prove the non-inferiority of prolgolimab 250 mg Q3W versus prolgolimab 1 mg/kg Q2W for the treatment of patients with unresectable or metastatic melanoma in terms of ORR according to RECIST 1.1. Patients from the MIRACULUM study (BCD-100-2/MIRACULUM, NCT03269565) comprised a historical control group., Results: One hundred fourteen patients received prolgolimab 250 mg Q3W, and 61 patients received prolgolimab (Prolgo) 1 mg/kg Q2W (historical control). Objective response was achieved by 33.3% [95% confidence interval (CI): 24.8, 42.8] of patients in the Prolgo 250 mg group compared with 32.8% (95% CI: 21.3, 46.0) of patients in the Prolgo 1 mg/kg group. Risk difference was 0.00, 95% CI (-0.12; NA), p = 0.0082. Both regimens were well tolerated, and safety profiles were comparable. The pharmacokinetic analysis (PK) showed that the regimen with the fixed dose of 250 mg Q3W was characterized by higher PK parameters. The immunogenicity study did not detect binding antibodies to prolgolimab in any of the subjects., Conclusion: The obtained results showed that the selected fixed dosing regimen of prolgolimab 250 mg Q3W is characterized by efficacy and safety parameters comparable to that observed for the 1 mg/kg Q2W regimen., Competing Interests: GK, NP, VM, SP, TS, AZ, NK, NF, DK, IB, DT, SO, AN, KV, YM, and LD report clinical trial investigator’s fee BCD-100-8/FLAT and honoraria from BIOCAD for participation as a speaker at scientific and educational meetings. YL, AZ-O, IS, AS, DL, VC, and AL are BIOCAD employees. The study was initiated, funded, and sponsored by JSC Biocad. Design and conduct of the study was undertaken by the sponsor in collaboration with investigators. The study investigators and their respective research teams collected the data; JSC Biocad compiled the data for summation and analysis. All authors were responsible for data interpretation., (Copyright © 2024 Demidov, Kharkevich, Petenko, Moiseenko, Protsenko, Semiglazova, Zimina, Kovalenko, Fadeeva, Kirtbaya, Belogortsev, Tantsyrev, Odintsova, Nesterova, Vorontsova, Makarycheva, Linkova, Zinkina-Orikhan, Siliutina, Sorokina, Liaptseva, Chistyakov and Lutsky.)

Aim: To investigate retrospectively the effects of bone metastases and bisphosphonates in sunitinib-treated metastatic renal cell carcinoma patients., Patients & Methods: Patients in Groups (Gp) 1 and 2, but not Gp3, had bone metastases. Gp2 received bisphosphonates following standard practice., Results: Gp2 had less favorable prognosis than Gp1. Gp3 had fewer metastases and the best prognosis. More serious adverse events occurred in Gp2 versus Gp1. The difference in overall survival between Gp1 and Gp2 was not significant after adjusting for covariates. Significantly shorter overall survival in Gp1 versus Gp3 persisted after adjusting for covariates., Conclusion: Bone metastases may have a negative prognostic impact in metastatic renal cell carcinoma. Bisphosphonates may have delayed early disease progression for prognostically worse sunitinib/bisphosphonate-treated patients.

Background: Although significant progress has been made for metastatic renal cell carcinoma (MRCC), very little progress has been achieved for non-clear cell MRCC. Thus, we performed a phase II, multicenter trial of capecitabine in patients with non-clear cell MRCC., Patients and Methods: Adult patients with MRCC containing <50% of clear cells were eligible. All patients received oral capecitabine (1,250 mg/m) twice daily for 14 days, followed by 14 days of rest. Primary end point was objective response rate. On the basis of Chen and Ng 2-stage accrual design, maximum planned enrollment was 51 patients. This study is registered with ClinicalTrials.gov, NCT01182142., Results: Fifty-one patients enrolled between February 2006 and January 2009. Most patients were men (72.5%), who had papillary RCC (76.5%), Memorial Sloan Kettering Cancer Center intermediate prognosis (86%), and had not been treated earlier (92%). The objective response rate was 26%. Two patients (4%) had a complete response. Stable disease was achieved in 24 (47%) patients. The median progression-free survival was 10.1 months [95% confidence interval (CI), 8.7-11.5], and overall survival was 18.3 months (95% CI, 15.5-21.1). The 1-year overall survival was 71% (95% CI, 63%-79%). Major grades 3 to 4, treatment-related toxicities included diarrhea (2%), esophageal mucosal inflammation (2%), hand-foot syndrome (4%), thrombocytopenia (9.8%), and neutropenia (8%). No patients were withdrawn because of laboratory abnormalities., Conclusions: Capecitabine has clinical activity in MRCC patients who have non-clear cell histology and a good or intermediate prognosis. Additional prospective randomized trial comparing capecitabine with placebo is required.

Introduction: Belarus, Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Republic of Moldova, Romania, Russian Federation, Serbia, Slovakia, Slovenia and the Ukraine represent a collection of Central and Eastern European (CEE) countries in which the epidemiology and treatment of cancer varies greatly between and within countries. Current challenges include non-adherence to current treatment guidelines, restrictions in access and reimbursement for new therapies, and a lack of basic oncology programs. Metastatic renal cell carcinoma (mRCC) is a malignancy with historically poor prognosis. In CEE countries, the incidence and mortality rates of mRCC are among the highest in the world. Fortunately, mRCC represents a cancer for which a number of new targeted therapies have recently demonstrated benefit, resulting in new evidence-based treatment guidelines. Incorporating these mRCC treatment recommendations into the routine care of patients with mRCC in CEE countries would represent a major step forward for cancer care in this region., Areas Covered: This review discusses the unique challenges faced by the aforementioned Eastern European countries in the treatment of metastatic renal cell cancer, in an attempt to assist health-care providers in providing the best care possible for their European patients., Expert Opinion: Despite a wealth of clinical trial data supporting the use of targeted therapies for first-line treatment of mRCC, cytokine-based immunotherapy is still used in some of these European countries. With implementation and adherence to existing guidelines, treatment can be clinically and economically optimized in patients with mRCC from this region.

Germ-line mutations of the BRCA1 gene are responsible for a substantial proportion of families with multiple cases of early-onset breast and/or ovarian cancer. Since the isolation of BRCA1 last year, >65 distinct mutations scattered throughout the coding region have been detected, making analysis of the gene time consuming and technically challenging. We have developed a multiplex heteroduplex analysis that is designed to analyze one-quarter of the coding sequence in a single-step screening procedure and that will detect approximately 50% of all BRCA1 mutations so far reported in breast/ovarian cancer families. We have used this technique to analyze BRCA1 in 162 families with a history of breast and/or ovarian cancer and identified 12 distinct mutations in 35 families.

Evidence for the role of dysplastic nevi (DN) in the development of cutaneous malignant melanoma (CMM) is presented. Primary multiple foci of CMM were found considerably more frequently in individuals with DN. The frequency of primary multiple CMM was found to be 3.1% in males with DN and 0.9% in males without DN; in females, 6.8 and 0.6%, respectively. Genetic correlation analysis was performed to determine the genetic interrelation between DN and CMM. In general, the genetic correlation coefficient was 0.9; i.e., predisposition to DN and CMM is determined by common genes for 90%. The frequency and distribution of constitutive fragile sites in chromosomes of peripheral lymphocytes was studied by the method of principal components for discrete variables. The site 1p22 is responsible for variability of the traits CMM and DN for 98.5%. On the one hand, this suggests that one of the supposed genes for CMM can be located at 1p22; on the other hand, CMM and DN are likely to have a common genetic determination or to be very tightly linked. Estimates of risk for the development of CMM in patients' relatives are given with reference to the variants of CMM manifestation and presence of DN.

Epidemiologic and clinical genetic data on cutaneous malignant melanoma (CMM) are presented. The incidence of CMM in Moscow from 1983 to 1987 was analyzed. Cumulative incidence (cumulative risk) was calculated for various life periods on the basis of estimates for various age groups, which were used as population frequencies. By the age of 85, these frequencies were 0.35% for males and 0.38% for females. Among relatives of patients, the incidence of CMM was 1.420 +/- 0.498% for males and 1.110 +/- 0.348% for females; i.e., the incidence exceeded the population frequency by a factor of 3 or 4. As a whole, the familial frequency of cancer was equal to 13.3% for male probands and 14.2% for female probands, i.e., more than three times higher than the population frequency. The data obtained formed the basis for the development of CMM classification. hereditary and nonhereditary variants of cutaneous melanoma were identified. Familial cases and CMM that occurred against the background of inherited disease or syndromes were classified as hereditary variants of CMM; taken together, they accounted for 38.8%. The data provided grounds for identification of families at increased risk for the development of CMM.