Search

Background: Second- or third-line treatment options for metastatic renal cell carcinoma (mRCC) have dramatically changed in the last few years. There are no criteria for the choice between nivolumab and cabozantinib, which both demonstrated overall survival (OS) gain in pivotal trials., Objective: We conducted an analysis of oncological outcomes in patients treated in the Veneto Region (Italy), studying different sequences of TKI-nivolumab-cabozantinib or TKI-cabozantinib-nivolumab in a publicly funded healthcare system., Patients and Methods: We conducted a retrospective, real-world analysis of all consecutive patients with mRCC treated with nivolumab or cabozantinib in 2017-2018 at 19 Oncology Units in the Veneto Region., Results: We identified 170 patients, 73 % males, median age 68.4 years. All patients started second-line treatment, 59 % received a third-line therapy. Patients with NLR > 3 had a shorter OS (p < 0.0001). In the second-line treatment, nivolumab was administered to 108 patients (63 %), cabozantinib to 29 (17 %); in the third-line treatment nivolumab was administered to 42 patients (25 %), cabozantinib to 49 (29 %). Median OS and PFS in second line treatment were 28.4 and 6.6 months for nivolumab, 16.8 and 6.6 months for cabozantinib. Median OS and PFS in third-line treatment were 27 and 5.2 months for nivolumab, 16.6 and 7.5 months for cabozantinib. Median OS for nivolumab>cabozantinib sequence versus cabozantinib > nivolumab was 28.8 versus 19.9 months (p = 0.2); median PFS for both the sequences were similar at 5.7 months. A cost effectiveness per month of survival of the two sequences analysis was performed: the cost per month for the nivolumab > cabozantinib sequence was 1738.60whereas the cost for the other one was €1624.80., Conclusions: In our real-world cohort, most patients received nivolumab as second-line treatment. Outcomes of single drugs are superimposable with those in the published literature. Both the sequences of nivolumab and cabozantinib appear to be viable, effective strategies from an OS and cost-effective perspective., (© 2022. The Author(s).)

Background: The CHAARTED and LATITUDE trials demonstrated improved outcomes with docetaxel or abiraterone plus androgen deprivation therapy in metastatic hormone sensitive prostate cancer (mHSPC) using two different prognostic scores., Objective: The aim of our study was to assess the concordance between the two scores and if these retained their prognostic value exclusively in de novo mHSPC., Patients and Methods: De novo mHSPC patients referring to our institution were retrospectively stratified according to the CHAARTED and LATITUDE classifications: high volume/high risk (HV/HR), low-volume/low-risk (LV/LR), and HVorHR (HV/LR and LV/HR). The Kaplan-Meier method and Cox proportional-hazard models were used to estimate hazard ratios for overall survival., Results: The study population included 106 patients. Concordance between the CHAARTED and LATITUDE classifications was observed in 86.8% of cases (65.1% HV/HR, 21.7% LV/LR), while 13.2% of patients fulfill the criteria of only one of the two classifications (HVorHR). When analyzed independently, the CHAARTED and LATITUDE classifications maintained their prognostic value (mOS 28.2 months in HV versus 60.9 months in LV, p = 0.006; 28.2 months in HR versus 40.6 months in LR, p = 0.017). The LR/LV population showed significantly longer mOS compared to the HR/HV group (72.6 months versus 26.3 months; p = 0.005), and to HVorHR patients (35.1 months; p = 0.003). No difference in OS was observed between HV/HR and HVorHR patients. ECOG PS ≥ 1 and patient age improved the prognostic value of the two classifications with multivariate analysis., Conclusions: Our study showed a lack of complete concordance between the CHAARTED and LATITUDE classifications. The analysis confirmed the role of these prognostic scores to stratify de novo mHSPC patients in clinical practice.

Despite the development of novel effective therapeutic strategies, metastatic castration-resistant prostate cancer (mCRPC) remains a disease with a lethal course and a high biological and molecular heterogeneity. To date, germline mutations in the BRCA gene represent one of the main risk factors for developing prostate cancer, with a strong association with aggressive phenotype and poor clinical outcomes. A better understanding of the genomic landscape of prostate cancer has strengthened the idea that "synthetic lethality" of this disease might be useful in cancer-drug discovery, focusing on agents such as platinum compounds and poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi). In this review, we summarize the main data available on BRCA mutations and discuss the clinical implications of these genomic aberrations in the management of prostate cancer, stressing the need to identify prognostic and predictive biomarkers and to deeply understand the mechanisms of treatment resistance, in order to maximize personalized medicine protocols and therefore clinical benefit.