RESUMEN

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.

RESUMEN

There is accumulating evidence that anemia and iron deficiency, thrombocytopenia, blood loss and coagulopathy are independent risk factors for adverse patient outcomes in oncology and other settings. Patient blood management (PBM) aims to address these factors by managing and preserving a patient's blood. PBM improves patient health, but also reduces resource utilization, including use of allogeneic blood components, which is another risk factor for adverse outcomes. Supported by the World Health Organization and endorsed in WHA63.12, PBM is recommended by an increasing number of health authorities and is about to become a new standard of care. In support of the Russian National Long-Term Oncology Strategy 2030 to improve quality of oncological care, and with support from the National Association of Specialists in PBM, the PBM Oncology Working Group of the Russian Federation was created. In July 2020, this Group met to discuss the rationale and need for PBM in Russian oncology care. The Group recommended to include PBM as an integral part of standard oncology treatment pathways and developed a national resolution as a call to action on this matter, which was adopted in August 2020. This article details the rationale behind the resolution, delineates the action required from facilitating stakeholders (government; healthcare providers; educational facilities; research entities/institutions; funders; patient representatives/advocates), and proposes a roadmap for implementation. The generation of local health-economic and outcome data and the development of educational programs will be important in the implementation of PBM to help alleviate the health, social and economic burden of cancer.

Asunto(s)

RESUMEN

Fifteen hypermucoviscous isolates (13 blaNDM-1-positive) obtained from 11 oncology patients were analyzed by whole genome sequencing, and selected isolates were assessed in a murine model of sepsis. ST395/K2 isolates harboring rmpA, rmpA2, peg-344, aerobactin, enterobactin, yersiniabactin, type I fimbriae, etc. displayed maximal virulence in the mouse lethality assay (LD50 = 102 CFU). ST147/K20 isolates lacking yersiniabactins were relatively less virulent (LD50 = 104 CFU), ST395/K2 isolates lacking rmpA, rmpA2, peg-344, and aerobactin, but harboring yersiniabactin demonstrated minimal virulence (LD50 = 105 CFU). Isolates represent various paths and stages of evolution directed towards convergence of multidrugresistant classical Klebsiella pneumoniae and hypervirulent K. pneumoniae.

Asunto(s)

RESUMEN

BACKGROUND: To assess safety, pathologic response rate, and long-term oncologic outcomes of radical prostatectomy (RP) after neoadjuvant chemotherapy using reduced-dose docetaxel without androgen-deprivation therapy in prostate cancer (PCa) patients of intermediate- and high-risk groups. METHODS: Forty-four patients with PCa (PSA > 10 ng/ml, Gleason score 7 or more, or clinical stage cT2c or more) were included with a median follow-up of 11.4 years after RP. One group (NCT/RP) received neoadjuvant treatment 3-weekly with docetaxel (36 mg/m(2) for up to six cycles, 21 patients), the other (control) group (RP, 23 patients) received RP only. RESULTS: Toxicities were mild with grade 3 events not exceeding 10%. A statistically significant reduction of PSA > 50% post-chemotherapy was observed in 52.4% cases. Cancer-specific survival (CSS) was 90% in the NCT/RP group and 60.9% in the RP group (P = 0.042). The biochemical recurrence-free survival was 68.5% in the NCT/RP and 37.7% in the RP groups; overall survival was 75.5% and 54.6%, respectively (both P > 0.05). CONCLUSIONS: The use of neoadjuvant chemotherapy before RP in a selected regimen and dose represents a safe strategy and results in benefits in CSS. Given the limitations of the study, this concept should be evaluated in large, prospective, controlled studies. Prostate 76: 1345-1352, 2016. © 2016 Wiley Periodicals, Inc.

Asunto(s)