We analyzed the cardiovascular toxicities related to the use of abiraterone and enzalutamide in prostate cancer. We found that these agents are associated with an increased risk of all- and ...high-grade cardiac toxicity as well as an increased risk of all- and high-grade hypertension. Follow-up for the onset of treatment-related cardiovascular events should be considered in these patients treated with abiraterone and enzalutamide.
The cardiovascular toxicity related to abiraterone and enzalutamide has been previously studied by our group. In this analysis, we aim to update our previous findings related to abiraterone and enzalutamide, including the new available evidence, both in castration-resistant and hormone-sensitive prostate cancer.
Prospective studies were identified by searching the MEDLINE/PubMed, Cochrane Library, and ASCO Meeting abstracts. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods.
We included 7 articles in this meta-analysis, covering a total of 8660 patients who were used to evaluate cardiovascular toxicity. The use of new hormonal agents was associated with an increased risk of all-grade (RR, 1.36; 95% CI, 1.13-1.64; P = .001) and high-grade (RR, 1.84; 95% CI, 1.21-2.80; P = .004) cardiac toxicity. The use of new hormonal agents was also associated with an increased risk of all-grade (RR, 1.98; 95% CI, 1.62-2.43; P = .001) and high-grade (RR, 2.26; 95% CI, 1.84-2.77; P = .004) hypertension compared with the controls. Abiraterone was found to significantly increase the risk of both cardiac toxicity and hypertension, whereas enzalutamide significantly increases only the risk of hypertension. No differences were found based on the dose of prednisone used with abiraterone. The major limitation of this study is that data are available only as aggregate, and no single-patient information could be analyzed.
Abiraterone and enzalutamide significantly increase the incidence and RR of cardiovascular toxicity in patients affected by metastatic prostate cancer. Follow-up for the onset of treatment-related cardiovascular events should therefore be considered in these patients.
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•Head-to-head comparisons do not exist for the newest treatments of metastatic renal cell carcinoma.•In our network meta-analysis, lenvatinib plus pembrolizumab has the highest probability to be the ...best choice.•This analysis could be used to help physicians while awaiting formal comparisons.•Nevertheless, our results do not aim to produce formal recommendations. Prospective comparison trials are needed.
Several first-line immune-checkpoints inhibitors (ICI) based combinations have been studied in metastatic renal cell carcinoma (mRCC) without any direct comparison between the regimens. The objective of this systematic review and network meta-analysis was to provide the most updated evidence about the preferred first line ICI-based regimen for mRCC.
We searched various databases, including PubMed, Web of Science and Scopus and the major conference proceedings (ASCO, ESMO). Eligible studies were randomized trial, published before June 2021 that evaluated first-line, ICI-based combinations compared with the standard of care in mRCC. Screening was performed independently by two investigators. A Cochrane risk-of-bias tool was used to assess trial quality. Relative effects of competing treatments were assessed by Bayesian network meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used. Outcomes included overall survival (OS), progression-free survival (PFS), overall response rate, complete response and adverse events.
Six trials with 5478 patients comparing 7 treatments were identified. Network meta-analysis showed that lenvatinib plus pembrolizumab had the highest probability to be the best treatment in terms of OS (surface under the cumulative ranking (SUCRA) 80.7%) and PFS (SUCRA 99.6%), while in sarcomatoid patients, nivolumab plus cabozantinib had the highest rank in terms of survival outcomes (SUCRA 85.8% and SUCRA 77.3%, respectively).
Although we established a ranking among new first-line mRCC treatment combinations, the absence of direct comparisons between the multiple treatment options represents a major hurdle in establishing optimal therapeutic sequences. Our results could represent a starting point for head-to-head trials between the most promising combinations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
TPS595
Background: Neoadjuvant chemotherapy (NACT) is a well-established treatment modality in MIBC but suffers from limited activity and significant toxicity. Recently, neoadjuvant immunotherapy ...(I/O) has demonstrated clinical safety and efficacy in various solid tumor indications including MIBC, with potentially less toxicity. Results from previous studies of single-agent I/O indicated a proportion of pathologic complete responses (ypT0N0) similar to that reported with NACT. Therefore, improving ypT0N0 responses remains a major task for successful treatment of MIBC in the future. Increasing evidence has emerged that Growth and Differentiation Factor 15 (GDF-15) plays a critical local immunosuppressive. Apart from blocking immune-cell entry into tissues GDF-15 also has major impact on the formation of the immune synapse. Many tumors overexpress GDF-15 and have hijacked this mechanism to block I/O therapy success. Various translational research efforts have indicated that GDF-15 may play a significant role for immunosuppression and T-cell exclusion in urothelial carcinoma (UC). Visugromab (CTL-002) is a GDF-15 neutralizing IgG4 monoclonal antibody that has demonstrated in Phase 1 a favorable safety profile and promising clinical activity with durable and deep responses in PD-1/PD-L1 relapsed/refractory metastatic solid tumors in combination with the anti-PD1 antibody Nivolumab (Nivo)*. This clinical trial is intended to investigate the combination of Visugromab with Nivo vs. Nivo monotherapy as neoadjuvant therapy for MIBC in patients (pts) who are ineligible for or elect not to undergo NACT. Primary endpoints are the complete pathologic response rate and radiologic response. Methods: This is a multi-center, parallel-cohorts and single-blinded Phase 2 study of neoadjuvant therapy in pts planned for radical cystectomy (RC). A total number of 30 subjects with stage T2-T4N0M0 MIBC will be enrolled and assigned 1:1 to receive either Nivo + Visugromab or Nivo + Placebo after stratification for CPS PD-L1 expression and cT-stage. No statistical assumptions have been undertaken at this stage. Treatment consists of three 4-week cycles i.v., Q4Wk, and RC is planned 4-8 weeks after last dose of study drug. After RC, pts will follow standard recommendations according to EAU guidelines. Primary endpoints are the proportion of ypT0N0 response and radiologic response rate. Secondary endpoints comprise additional efficacy parameter, surgical and medical safety, PK and PD assessments. Translational research includes evaluation of immunologic parameters in the tumor, other immune-correlates and molecular profiles, as well as evaluation of treatment-emergent cytokine and chemokine profiles in peripheral blood. * Melero et al., Annals of Oncology (2022) 33 (suppl_7): S331-S355.
Prostate cancer (PC) is a heterogeneous disease that requires a personalized treatment approach for proper patient management.
We analyzed a selected overview of the most important news recently ...presented at the 2021 ASCO genitourinary cancer symposium.
In particular, we focused on the identification of predictive biomarkers as potential targets for therapy. Molecular signatures of increased T cell activity, proliferation, and hormone dependence were associated with greater probability of response to apalutamide in non-metastatic CRPC. Pathogenic variants of DDR genes mutations detected with circulating tumor DNA (ctDNA) analysis, which had a high concordance with tumor tissue analysis, might represent a useful way for selecting mutated patients for poly (adenosine diphosphate ADP-ribose) polymerase (PARP) inhibitors therapy. Loss of PTEN could be a target for ipatasertib (a pan-AKT inhibitor) associated with abiraterone in mCRPC patients.
The 2021 ASCO Genitourinary Cancers Symposium significantly contributed to the complex research goal of intimately understanding PC carcinogenesis with the ultimate aim of improving patient outcomes.
This article describes the main acquisitions of renal cell carcinoma (RCC) management presented during the 2023 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. In ...particular, the efficacy of adjuvant pembrolizumab in patients with resected renal cell carcinoma (RCC) at increased risk of recurrence was confirmed through a subgroup analysis. In the metastatic setting, the updated analysis of the CheckMate 9ER study confirmed the efficacy in terms of overall survival (OS) of the combination of nivolumab plus cabozantinib; of note, this survival advantage was clear in the subgroup of patients at poor IMDC prognosis, but not in favorable IMDC risk group patients. As concern the triplet therapy (i.e. nivolumab+ipilumumab+cabozantinib), the updated analysis of the COSMIC-313 study confirmed a significant PFS advantage in the subgroup of mRCC patients at intermediate IMDC risk, while the lack of benefit in the poor risk group supports the critical role of immunotherapy (but not of VEGFR-TKIs) in this poor prognosis subgroup of patients. Finally, the activity of cabozantinib as second-line therapy after progression to ICI-based combinations was prospectively assessed. This 2023 ASCO Genitourinary Cancer Symposium laid the foundations for further knowledge development necessary for an increasingly personalized management of mRCC.
•De novo mCSPC accounts for about 4% of all prostate tumors.•De novo mCSPC is a heterogeneous disease, including indolent to rapidly fatal forms.•No validated prognostic models characterize the ...clinical course of de novo mCSPC.•ADT, ADT plus docetaxel, or ADT plus abiraterone are potential therapeutic options.•Understanding the most appropriate therapy for each patient is an unsolved issue.•Ongoing trials are currently investigating potential novel approaches for mCSPC.
De novo metastatic castration sensitive prostate cancer (mCSPC) accounts for about 4% of all prostate tumors in Western Countries. This condition has a heterogeneous biological e clinical behavior, ranging from indolent to aggressive and rapidly fatal forms. Recently, the therapeutic landscape for mCSPC has been broadly enriched; indeed robust evidence supports the addiction of chemotherapy (docetaxel) or abiraterone acetate to androgen deprivation therapy (ADT), the latter considered for long the unique standard of care. However, the prognostic stratification and the definition of the ideal therapeutic approach for the subpopulation of de novo mCSPC – albeit largely represented in pivotal clinical trials enrolling mCSPC patients – have yet to be prospectively outlined. The aim of this review was to describe the current state of art about clinical presentation, prognostic classification, and different therapeutic options available for de novo mCSPC patients. Furthermore, we shed light on ongoing clinical trials and future perspectives for this disease setting.
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