Purpose: an assessment of efficacy and safety of cabozantinib in unselected patients with metastatic renal cell carcinoma in the first and subsequent lines of therapy. Materials and methods. Russian multicenter observational study included 92 consecutive patients with morphologically verified metastatic renal cell carcinoma treated with cabozantinib (60 mg/d) in 16 Russian centers. Median age of the patients was 56 (19-79) years, a male-to-female ratio - 3:1. At the start of cabozantinib therapy 27.2 % of patients had ECOG PS 2. Most common histological type of kidney cancer was clear-cell RCC (90.2 %). Most patients were diagnosed with synchronous (71.7 %) multiple metastases (60.9 %). Previous nephrectomy was performed in 87.0 % of cases. Prognosis according to International Metastatic Renal Cancer Database Consortium (IMDC) score was assessed as favorable in 5.4 %, intermediate - in 58.7 % and poor - in 35.9 % patients. Cabozantinib as the first-line therapy was administered in 9 (9.8 %), following 1-5 lines of systemic treatment - in 83 (90.2 %) cases. Median follow-up was 11 (2.3-44.5) months. Results. In patients, receiving cabozantinib as the first-line therapy, objective response rate was 66.7 %, tumor control was reached in 100 % of cases. Median time to the objective response was 2.6 (1.9-3.6) months, median objective response duration - 13.2 (6.2-21.5) months. Median progression-free survival (PFS) and overall survival (OS) were not reached, 6- and 12-months PFS was 77.8 % and 77.8 %, 6- and 12-months OS - 88.9 % and 88.9 % respectively. Cabozantinib as the second and subsequent lines of therapy provided objective response rate of 34.9 %, tumor control rate - 97.6 %. Median time to the objective response was 2.5 (1.8-4.1) months, median objective response duration - 12.6 (5.5-27.3) months. Median PFS was not reached (6- and 12-months PFS - 92.5 % and 73.1 % respectively), median OS was 32.6 months (6- and 12-months OS - 97.4 % and 80.8 % respectively). Any adverse events (AE) developed in 88.8 %, AE grade III-IV - in 32.6 % of cases. Most frequent AE grade III-IV included arterial hypertension (18.5 %), diarrhea (6.5 %) and palmar-plantar erythrodysesthesia (6.5 %). Unacceptable toxicity demanded treatment cancellation in 2.2 %, therapy interruption - in 16.3 % and dose reduction - in 30.4 % of patients. Conclusion. Cabozantinib as the first and subsequent lines of therapy for metastatic renal cell carcinoma patients in the real world practice demonstrated high efficacy and better tolerability comparing with population assigned for cabozantinib monotherapy in the randomized phase II-III trials.

Aim. To assess the safety and to analyze an influence of cabozantinib monotherapy toxicity on treatment efficacy in unselected Russian patients with metastatic renal cell carcinoma (mRCC). Materials and methods. Medical data of 92 patients with verified mRCC were included in the study. The median age of the patients was 56 (1979) years, most of them - 60 (65.2%) were of male gender. Twenty five (27.2%) persons had Eastern Cooperative Oncology Group performance status (ECOG PS). At the time of cabozantinib monotherapy start 5 (5.4%) patients had favorable, 54 (58.7%) intermediate, and 33 (35.9%) unfavorable prognosis by International Metastatic Renal Cancer Database Consortium (IMDC) model. Eighty-three (90.2%) patients were pretreated, including 76 (82.6%) patients who previously received anti-angiogenic agents. All patients were administered with cabozantinib monotherapy (60 mg/day); dose adjustment was performed according to the instruction. Results. Adverse events (AEs) were reported in 81 (88.0%) of 92 patients; 30 (32.6%) AEs were grade 34. Toxicity-related dose reduction of cabozantinib was required in 28 (30.4%), treatment interruption in 15 (16.3%), and discontinuation in 2 (2.2%) patients. The most common AEs were hypertension (69 patients, 75.0%), asthenia (47 patients, 51.1%), diarrhea (43 patients, 46.7%), and palmar-plantar erythrodysesthesia (43 patients, 46.7%). The most common severe AEs were: arterial hypertension (17 patients, 18.5%), diarrhea (6 patients, 6.5%), and palmar-plantar erythrodysesthesia (2 patients, 2.2%). The most frequent laboratory abnormalities during therapy were elevated serum transaminases (33 patients, 35.9%), anemia (13 patients, 14.1%), and thrombocytopenia (10 patients, 10.9%). No previously unreported AEs or laboratory abnormalities were observed. There was a significant increase in progression-free survival (hazard ratio 2.5; 95% confidence interval 1.05.9; p=0.046) and overall survival (hazard ratio 3.0; 95% confidence interval 1.28.3; p0.025) in patients with treatment-related arterial hypertension. Conclusion. The observational study confirmed the acceptable safety profile of cabozantinib in the first and subsequent lines of treatment in mRCC patients. No new safety signals were identified. Treatment-related arterial hypertension may be a favorable predictor of survival.

The following review presents a problem of metastatic castration-resistant prostate cancer and its association with germline or somatic mutations in homologous recombination repair (HRR). In 2020, olaparib was approved in the Russian Federation as a monotherapy for metastatic castration-resistant prostate cancer with germline or somatic mutations of genes involved in DNA repair by homologous recombination, after progression on therapy with new hormonal drugs. We describe a review of the main olaparib clinical trials assessing its efficacy, safety and tolerance in metastatic castration-resistant prostate cancer patients.

This review of renal cell carcinoma describes new diagnostics and treatment standards, new guidelines from international professional organizations and key studies, published in 2019.

Objective: a preliminary assessment of safety, tolerability, and efficacy of lenvatinib in combination with everolimus in unselected patients with metastatic renal cell carcinoma (mRCC) resistant to antiangiogenic targeted therapy.Materials and methods. We analyzed medical data of 19 consecutive mRCC patients received lenvatinib in combination with everolimus following antiangiogenic targeted therapy failure. Median age was 55 (23–73) years. ECOG PS 0–1 was in 11 (57.9 %), ECOG 2–4 – in 8 (42.1 %) cases. Four (21.1 %) patients were distributed into the good, 10 (52.6 %) – into the intermediate, and 5 (26.3 %) – into the poor IMDC (International Metastatic Renal Cancer Database Consortium) prognostic group. Multiple metastases were diagnosed in 18 (94.7 %), multiple metastatic sites – in 17 (89.5 %), liver metastases – in 6 (37.6 %) cases. All the patients were previously treated with 1–4 lines of therapy (≥2 – 12 (63.1 %)). Median follow-up was 5 (2–10) months.Results. By the time of the analysis 12 (63.2 %) patients are being treated, 7 (36.8 %) – completed combined treatment (due to RCC progression – 4 (21.1 %), toxicity – 2 (10.5 %), death from unrelated reason – 1 (5.3 %)). Median time of completed therapy was not reached, mean treatment time was 5.1 (1.9–11.2) months. Adverse events were registered in 17 (89.5 %) patients (grade III – 3 (15.8 %), grade IV – 0, grade V – 1 (5.3 %)). The most common adverse events were diarrhea (68.4 %), stomatitis (57.9 %), hypertension (42.1 %), and weight loss (47.4 %). Lenvatinib or everolimus dose reduction was demanded in 5 (26.3 %) and 0, therapy interruption – in 5 (26.3 %) and 1 (5.3 %) patient respectively. Maximal response was assessed as partial in 1 (5.3 %) and stabilization – in 18 (94.7 %) cases. Decline of metastases size was registered in 12 (63.2 %) (median – 17 % (3–40 %)), stabilization – in 8 (42.1 %), enlargement – in 1 (5.3 %) patient. Median time to maximal response was 2 (2–4) months. Five-months overall and progression-free survival rates were 76.1 and 87.4 % respectively. Following 2 cycles of combined therapy ECOG PS improved in 11 (57.9 %), stabilized – in 6 (31.6 %), worsened – in 2 (10.5 %) patients.Conclusion. Our preliminary data have confirmed antitumor activity and showed acceptable tolerability of lenvatinib in combination with everolimus in unselected patients with mRCC resistant to antiangiogenic targeted therapy.

Objective. Evaluation of utility and safety of salvage cystectomy after organ preservation treatment in patients with muscle-invasive bladder cancer.Materials and methods. A retrospective study included data on 130 patients with transitional cell carcinoma treated at the N.N. Blokhin Russian Cancer Research Center in 1981-2016. The main group included 66 patients who underwent salvage cystectomy after unsuccessful organ preservation treatment based on beam radiation therapy. Lymph node dissection was performed in 42 (63.6 %) patients. For the purposes of urinary diversion 42 (63.6 %) patients received ileal conduit (Bricker procedure), 7 (10.6 %) - Studer deal neobladder, 17 (25.8 %) - other treatment. Bladder cancer was morphologically confirmed in 62 (93.9 %) samples (P1 stage - 6 (9.1 %), P2 - 21 (31.8 %), P3 - 25 (37.9 %), P4 - 18 (27.2 %)); lymph node metastases were discovered in 11 (16.6 %) cases. Anaplasia grade was G(3) in 35 (56.5 %) of the 62 samples containing tumor. Control group included 64 patients who underwent radical cystectomy without previous treatment. Rates of T3a-4b categories and G3 anaplasia grade were significantly higher in the main group (p < 0.0001).Results. Rate of intraoperative complications of salvage cystectomies was 10.6 %, postoperative - 42.7 % (28 of 65) (severity grade I-II in 27.3 % (18 of 28) of cases, severity grade III-V in 15.4 % (10 of 28) of cases). Five-year total, specific and relapse-free survival in the main group was 43.7, 58.6 and 54.7 %, respectively. Independent factors of favorable prognosis for survival were anaplasia grade G(1-2), hydronephrosis and lymph node dissection. Recurrences after salvage surgeries were less frequent than after cystectomies performed without previous treatment (19 (30.6 %) and 31 (48.4 %), respectively, p = 0.031). No other statistically significant differences between salvage and radical cystectomies were observed.Conclusion. Salvage cystectomy after unsuccessful organ preservation treatment in patients with muscle-invasive bladder cancer is associated with acceptable surgical risk and provides satisfactory long-term results comparable with radical cystectomy.