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Background: The RCC treatment landscape has evolved dramatically over the past decade. The purpose of this study is to present a real-world data estimation of RCC's cost-of-illness for this tumour's clinical pathway., Methods: This investigation is a population-based cohort study using real-world data, which considers all RCC incident cases diagnosed in Local Unit 6 of the Province of Padua in 2016 and 2017 as registered by the Veneto Cancer Registry. Data on drug prescriptions, the use of medical devices, hospital admissions, and visits to outpatient clinics and emergency departments were collected by means of administrative databases. We evaluated the costs of all healthcare procedures performed in the 2 years of follow-up post-RCC diagnosis. The overall and annual average real-world costs per patient, both as a whole and by single item, were calculated and stratified by stage of disease at diagnosis., Results: The analysis involved a population of 148 patients with a median age of 65.8 years, 66.22% of whom were male. Two years after diagnosis, the average total costs amounted to €21,429 per patient. There is a steady increment in costs with increasing stage at diagnosis, with a total amount of €41,494 spent 2 years after diagnosis for stage IV patients, which is 2.44 times higher than the expenditure for stage I patients (€17,037). In the first year, hospitalization appeared to be the most expensive item for both early and advanced disease. In the second year, however, outpatient procedures were the main cost driver in the earlier stages, whereas anticancer drugs accounted for the highest costs in the advanced stages., Conclusions: This observational study provides real-world and valuable estimates of RCC's cost-of-illness, which could enable policymakers to construct dynamic economic cost-effectiveness evaluation models based on real world costs' evaluation., (© 2022. The Author(s).)

Background: The phase II TALAPRO-1 study (NCT03148795) demonstrated durable antitumor activity in men with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). Here, we detail the safety profile of talazoparib., Patients and Methods: Men received talazoparib 1 mg/day (moderate renal impairment 0.75 mg/day) orally until radiographic progression, unacceptable toxicity, investigator decision, consent withdrawal, or death. Adverse events (AEs) were evaluated: incidence, severity, timing, duration, potential overlap of selected AEs, dose modifications/discontinuations due to AEs, and new clinically significant changes in laboratory values and vital signs., Results: In the safety population (N = 127; median age 69.0 years), 95.3% (121/127) experienced all-cause treatment-emergent adverse events (TEAEs). Most common were anemia (48.8% [62/127]), nausea (33.1% [42/127]), decreased appetite (28.3% [36/127]), and asthenia (23.6% [30/127]). Nonhematologic TEAEs were generally grades 1 and 2. No grade 5 TEAEs or deaths were treatment-related. Hematologic TEAEs typically occurred during the first 4-5 months of treatment. The median duration of grade 3-4 anemia, neutropenia, and thrombocytopenia was limited to 7-12 days. No grade 4 events of anemia or neutropenia occurred. Neither BRCA status nor alteration origin significantly impacted the safety profile. The median (range) treatment duration was 6.1 (0.4-24.9) months; treatment duration did not impact the incidence of anemia. Only 3 of the 15 (11.8% [15/127]) permanent treatment discontinuations were due to hematologic TEAEs (thrombocytopenia 1.6% [2/127]; leukopenia 0.8% [1/127])., Conclusion: Common TEAEs associated with talazoparib could be managed through dose modifications/supportive care. Demonstrated efficacy and a manageable safety profile support continued evaluation of talazoparib in mCRPC., Clinicaltrials.gov Identifier: NCT03148795., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Nivolumab and cabozantinib are currently approved agents in metastatic renal cell carcinoma (mRCC) but there are no data available for patients progressing to both treatments. The aim of this study was to compare active therapeutic options and best supportive care (BSC) after progression to nivolumab and cabozantinib in mRCC., Methods: In this retrospective study, we selected 50 patients from eight Italian centers. The primary endpoint of the study was the overall survival (OS) of patients on active treatment versus BSC. Secondary endpoints were the progression-free survival (PFS) and objective response rate (ORR). The efficacy of active therapy was also investigated., Results: After progression to both nivolumab and cabozantinib, 57.1% of patients were given active treatment (mainly everolimus and sorafenib) while 42.9% received BSC. The median OS was 13 months (95% CI: 4-NR) in actively treated patients and 3 months (95% CI: 2-4) in BSC patients (p = 0.001). Patients treated with sorafenib had better disease control than those treated with everolimus (stable disease: 71.4% vs. 16.7%, progression disease: 14.3% vs. 58.3%; p = 0.03), with no significant differences in PFS (5 and 3 months, 95% CI: 1-6 vs. 2-5; p = 0.6) and OS (12 and 4 months, 95% CI: 3-NR vs. 2-NR; p = 0.2)., Conclusion: After treatment with both nivolumab and cabozantinib, the choice of a safe active systemic therapy offered better outcomes than BSC., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aims: Data regarding the cardiac toxicity of cabozantinib lacks. The aim of our study was to assess the risk of cabozantinib-related cardiotoxicity in mRCC patients., Methods: We performed a multicentre prospective study on mRCC patients treated with cabozantinib between October 2016 and November 2017. Transthoracic echocardiogram and plasma biomarkers assay were assessed at baseline, 3 and 6 months after cabozantinib initiation., Results: The study population included 22 mRCC patients. At baseline, 9.1% had a reduced left ventricular ejection fraction (LVEF), but none had a left ventricular systolic dysfunction. Patients with baseline reduced LVEF did not show further significant LVEF modification after 3 months. After 6 months, only 1 had an LVEF decline >10% compared to baseline, resulting in LV systolic dysfunction. At baseline, 64.7% and 27.3% of patients had elevated precursor brain natriuretic peptide (proBNP) and high-sensitivity troponin I (hsTnI), respectively. Among patients with basal normal proBNP and hsTnI, none had elevated values at 3 and 6 months. No correlation was found between basal elevated proBNP and basal reduced LVEF (P = .29), and between elevated proBNP and reduced LVEF after 6 months (P = .37). Similarly, we found no correlations between elevated hsTnI and reduced LVEF or elevated proBNP at baseline (P = .47; P = .38), at 3 (P = .059; P = .45) and after 6 months (P = .72; P = 1.0)., Conclusions: This prospective study revealed a modest risk of developing left ventricular systolic dysfunction related to cabozantinib. A lack of correlation between elevated cardiac biomarkers and reduced LVEF at different time-points was detected. Assessments of the cardiac function should be reserved at the occurrence of clinical symptoms., (© 2019 The British Pharmacological Society.)

Background: Recently, immune checkpoint inhibitors against PD-1/PD-L1 or CTLA4 have emerged as new treatments for metastatic renal cell carcinoma (mRCC), despite discrepancy between their effects on OS and PFS. We performed a meta-analysis of randomized trials comparing immunotherapy to standard of care (SOC) in mRCC., Methods: Searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts prospective studies were identified. Data extraction was conducted according to the PRISMA statement. The measured outcomes were OS, PFS, and ORR., Results: A total of 2832 patients were available for evaluation of OS, and 3033 for PFS and ORR. Compared to SOC, immunotherapy improved OS (HR = 0.75; 95%CI 0.66-0.85; p < 0.001), and PFS (HR = 0.88; 95%CI 0.80-0.97; p = 0.009). The PFS benefit was not confirmed when considering patients treated in first-line only (p = 0.10). Conversely, significant ORR improvement was found in patients treated in first-line only (HR = 1.14; 95%CI 1.02-1.28; p = 0.03) but not in the overall population., Conclusions: Immunotherapy improved OS compared to SOC in mRCC, irrespective of treatment line. In first-line, immunotherapy also increased the ORR compared to sunitinib. A lack of correlation between OS and PFS was confirmed, the latter to be used cautiously for the design and interpretation of trials involving immunotherapy in mRCC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: Monoclonal antibodies (mAbs) directed against PD-1/PD-L1 have recently entered the therapeutic algorithm of several solid tumors. Among treatment-related adverse events pulmonary toxicity (PT) is of particular interest. We assess the incidence and relative risk (RR) of PT in patients treated with anti-PD1/PD-L1 mAbs., Results: 11 articles were selected. The incidence of any- and high-grade PT was low (2.9 and 1.0%, respectively). Compared with standard therapies, anti-PD-1 mAbs do not significantly increase the risk of both any-grade (RR: 2.65; p = 0.06) and high-grade PT (RR: 1.40; p = 0.25). Of note, the RR: of developing any-grade (RR: 3.13; p < 0.0001) and high-grade (RR: 2.42; p = 0.03) PT significantly increased when excluding the Checkmate-025 trial, with everolimus as control therapy. No differences were identified between the type of mAbs, the tumor type and treatment duration for both any-grade and high-grade PT.