Thromboembolic risk in prostate cancer patients treated with PARP inhibitors: A systematic review and meta-analysis.

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) have been associated with thrombotic events, although the association with thrombosis risk in different cancers remains poorly defined. METHODS: This meta-analysis included phase II and phase III clinical trials in which patients with metastatic prostate cancer were treated with PARPi either as monotherapy or in combination. The primary endpoints were the rates of thromboembolic events in prostate cancer patients. RESULTS: A total of 2210 and 1662 patients with prostate cancer were compared in the PARP inhibitor and control groups, respectively. 96 (4.3 %) and 37 (2.2 %) patients had thrombosis in the PARPi and control groups, respectively. PARPi had a statistically significant increased risk of thrombosis in prostate cancer patients (Odds Ratio (OR)=1.98, 95 % CI: 1.06-3.70, P=0.030). CONCLUSION: The heightened thrombotic risk associated with PARPi treatment in prostate cancer emphasizes the need for comprehensive management protocols to effectively reduce the risk and ensure safer outcomes.

Impact of antihistamine use on the survival outcomes of immune checkpoint inhibitors in advanced cancer patients.

Histamine and H1 receptors play a crucial role in the tumor microenvironment. Preclinical data showed that concomitant use of antihistamines and immune checkpoint inhibitors (ICIs) might increase the effect of ICIs. This study aimed to evaluate the impact of antihistamines on the oncological outcomes of ICIs. This retrospective study was conducted in a tertiary cancer center. Advanced cancer patients treated with ICIs were included in this study. A total of 133 patients receiving ICIs in the metastatic setting were included. Melanoma (33.1%) was the most common tumor type. The most common ICI was nivolumab (63.2%). Fifty-five (38.4%) patients received antihistamines concomitantly with ICIs. The most common antihistamine was pheniramine (85.5%). The median progression-free survival (PFS) (8.2 vs. 5.1 months, P  = 0.016) and overall survival (OS) (16.2 vs. 7.7 months, P  = 0.002) were longer in patients receiving antihistamines concomitantly with ICIs. In multivariate analysis, PFS [hazard ratio (HR) = 0.63, 95% CI: 0.40-0.98, P  = 0.042] and OS (HR = 0.49, 95% CI: 0.29-0.81, P  = 0.006) were also better in those patients after adjusting for confounding factors, such as performance status, bone or liver metastasis, and concurrent chemotherapy. This study suggested that antihistamines may enhance the efficacy of ICIs in patients with advanced cancer. If validated in prospective trials, antihistamines and ICIs combinations might be new options to improve oncological outcomes.

Clinical Features and Prognostic Factors of Metastatic Non-Clear Cell Renal Cell Carcinoma: A Multicenter Study from the Turkish Oncology Group Kidney Cancer Consortium.

INTRODUCTION: We aimed to evaluate clinical features, prognostic factors, and treatment preferences in patients with non-clear cell renal cell carcinoma (nccRCC). METHODS: Patients with metastatic nccRCC were selected from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database. Clinical features, prognostic factors, and overall survival (OS) outcomes were investigated. RESULTS: A total of 118 patients diagnosed with nccRCC were included in this study. The median age at diagnosis was 62 years (interquartile range: 56-69). Papillary (57.6%) and chromophobe tumors (12.7%) are common histologic subtypes. Sarcomatoid differentiation was present in 19.5% of all patients. When the patients were categorized according to the International Metastatic RCC Database Consortium (IMDC) risk scores, 66.9% of the patients were found to be in the intermediate or poor risk group. Approximately half of the patients (55.9%) received interferon in the first line. At the median follow-up of 53.2 months (95% confidence interval [CI]: 34.7-71.8), the median OS was 19.3 months (95% CI: 14.1-24.5). In multivariate analysis, lung metastasis (hazard ratio [HR]:2.22, 95% CI: 1.23-3.99) and IMDC risk score (HR: 2.35, 95% CI: 1.01-5.44 for intermediate risk; HR: 8.86, 95% CI: 3.47-22.61 for poor risk) were found to be independent prognostic factors. CONCLUSION: In this study, survival outcomes are consistent with previous studies. The IMDC risk score and lung metastasis are the independent prognostic factors for OS. This is an area that needs research to better treat this group of patients and create new treatment options.

The benefit of treatment beyond progression with immune checkpoint inhibitors: a multi-center retrospective cohort study.

OBJECTIVE: Treatment beyond progression (TBP) with immune checkpoint inhibitors (ICIs) is an evolving field due to the limitations of conventional imaging in response evaluation. However, real-life data on the benefit of TBP is scarce, especially from the limited resource settings and patients treated in the later lines. Therefore, we aimed to investigate the survival benefit of TBP with ICIs in patients with advanced tumors from a limited resource setting. METHODS: For this multi-center retrospective cohort study, we included 282 patients treated with ICIs and had radiological progression according to RECIST 1.1 criteria. We evaluated post-progression survival according to the use of TBP (TBP and non-TBP groups) with univariate and multivariate analyses. RESULTS: The cohort's median age was 61, and 84.4% were treated in the second or later lines. 82 (29.1%) of 282 patients continued on ICIs following the initial progression. In multivariate analyses, patients in the TBP group had improved post-progression survival compared to non-TBP (13.18 vs. 4.63 months, HR: 0.500, 95% CI: 0.349-0.717, p < 0.001). The benefit of the TBP was independent of the tumor type, treatment line, and age. Furthermore, TBP with ICIs remained associated with improved post-progression survival (HR: 0.600, 95% CI: 0.380-0.947, p = 0.028) after excluding the patients with no further treatment after progression in the non-TBP arm. CONCLUSIONS: In this study, we observed that patients receiving ICIs beyond progression had considerably longer survival. Continuation of ICIs after progression should be considered a reasonable management option for patients with advanced cancer, specifically for patients with limited alternative options.

The relationship between systemic immune inflammation index and survival in patients with metastatic renal cell carcinomatreated withtyrosine kinase inhibitors.

This study aims to investigate the prognostic value of the systemic immune-inflammation index (SII)and its impact on survival in patients with metastatic renal cell carcinoma (mRCC). A total of 706patients with mRCC treated with tyrosine kinase inhibitors (TKIs)between January 2007 and June 2020 (i.e., sunitinib, pazopanib) were included in this study. SII was calculated in 621 patients with the following formula:[neutrophil (cellsx109/L) x platelet (cellsx109/L)] / lymphocyte (cellsx109/L).All patients were classified into SII-high and SII-low groups based on the cut-off value of SII at 756, which was the median SII level of our study group. The minimal follow-up duration was 10 months in all cohorts. The median age of patients was 60 (interquartile range (IQR):53-67) years. Three out of four patients were male. The majority of patients (85.7%) had clear cell histology, and sarcomatoid differentiation was observed in 16.9% of all patients. There were 311 and 310 patients in the SII-low and SII-high groups, respectively. In general, baseline characteristics were similar in each group. However, the rate of patients treated with sunitinib (63.3% vs. 49.0%, p < 0.001) and those who underwent nephrectomy (83.6% vs. 64.2%, p < 0.001) was higher in the SII-low group than in the SII-high group. On the other hand, patients with the IMDC poorrisk (31.6% vs. 8.0%, p < 0.001), those with bone (51.8% vs. 32.2%, p < 0.001) or central nervous system (12.9% vs. 5.8%, p = 0.026) metastasis, and those with Eastern Cooperative Oncology Group(ECOG) 2-4 performance score (28.1% vs.17.7%, p = 0.002) were more common in the SII-high group than in the SII-low group. The median overall survival (OS) was longer in the SII-low group than in the SII-high group (34.6 months vs. 14.5 months, p < 0.001). Similarly, the median progression-free survival (PFS) was longer in the SII-low group than in the SII-high group (18.0 months vs. 7.7 months, p < 0.001).In multivariableanalysis, SII was an independent prognostic factor for OS (hazard ratio (HR):1.39, 95% confidence interval (CI):1.05-1.85, p = 0.01) and PFS (HR:1.60, 95% CI:1.24-2.05, p < 0.001).Pre-treatment level of high SII might be considered a predictor of poor prognosisin patients with mRCC treated with TKIs.

Chronic hyperglycemia based on diabetes is independently associated with decreased survival in patients with advanced cancer treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have started a new era in treating patients with cancer. The effect of comorbidities and concomitant drug use on ICIs have become of interest in those patients. Data about the impact of hyperglycemia on response to ICIs in cancer patients are limited. All advanced-stage cancer patients treated with ICIs in Ankara University Medical Oncology Department were retrospectively evaluated. Patients treated in expanded access programs or clinical trials were excluded from the study. A total of 137 patients were included in this study. The most common primary tumor type was malign melanoma (32.8%) and nivolumab (62.3%) was the most common used ICI. More than half of patients (57.7%) had lung metastasis at the initiation of ICIs. Thirty-five patients (25.5%) had diabetes before initiating ICIs. Median baseline fasting glucose level was higher in patients with diabetes than those without diabetes (117 mg/dl vs. 99 mg/dl, P = 0.002). In all patients, median overall survival and progression-free survival were 11.3 [95% confidence interval (CI), 8.1-14.4) and 5.9 (95% CI, 3.6-8.3) months, respectively. In multivariate analysis, diabetes was found to increase risk of death [hazard ratio (HR), 2.09; 95% CI, 1.27-3.43, P = 0.004) and disease progression (HR, 2.01, 95% CI, 1.29-3.09, P = 0.002). Hyperglycemia might decrease response to ICIs in patients with advanced cancer. This research area is still an unmet need in the immunotherapy era. Prospective studies are needed to elucidate the effect of hyperglycemia on the response to ICIs.

Prognostic role of pan-immune-inflammation value in patients with metastatic castration-resistant prostate cancer treated with androgen receptor-signaling inhibitors.

AIM: To assess the prognostic effect of pan-immune inflammation value (PIV) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA) or enzalutamide. METHODS: Patients with mCRPC treated with AA or enzalutamide between January 2010 and June 2021 were included in this study. The most recently examined complete blood count values in the 1-month period before treatment were used for calculating PIV. The relationship between overall survival (OS) and PIV was evaluated by multivariate analysis. By using PIV and lactate dehydrogenase (LDH) levels which had shown survival effect at multivariate analysis, PIV-LDH combined score was established. RESULTS: A total of 114 patients were included in this study. At the median follow-up of 34.6 months (95% confidence interval [CI]: 32.4-36.8), the median OS was 21 months (95% CI: 17.6-21.3). The median OS in the low-PIV group was significantly higher than in the high-PIV group (34.4 months (95% CI: 21.3-47.5) vs. 14.3 months (95% CI: 10.0-18.7), p < 0.001). In the multivariate analysis for OS, high PIV (hazard ratio [HR]: 1.86, 95% CI: 1.11-3.13, p = 0.018) and LDH value 1.5 times the upper limit of normal and above (HR: 3.65 95%, CI: 1.86-7.16, p < 0.001) were associated with shorter OS. When survival analysis was performed according to the PIV-LDH combined score, the median OS was 34.4 months (95% CI: 22.2-46.6) in the low-risk group, 17.7 months (95% CI: 11.7-23.6) in the intermediate-risk group, and 8.4 months (95% CI: 5.1-11.7) in the high-risk group (p < 0.001). The C-index of the combined PIV-LDH score was higher than the C-index of PIV (0.65 vs. 0.61). CONCLUSION: In this study, we demonstrated that PIV was an independent prognostic factor for OS in patients with mCRPC treated with AA or enzalutamide. Additionally, PIV-LDH combined score may be considered a promising composite peripheral blood-based biomarker to predict OS in those patients.