Emerging Strategies in Adjuvant Immunotherapy: A Comparative Review of Bladder Cancer and Renal Cell Carcinoma Treatments.

Recent progress in adjuvant immunotherapy offers hope for improving disease-free survival in high-risk bladder cancer (BC) and renal cell carcinoma (RCC). This review focuses on key trials such as CheckMate 274 and KEYNOTE-564, which show promising results with nivolumab in BC and pembrolizumab in RCC, including a 30% reduction in progression risk. Pembrolizumab also demonstrated overall survival (OS) benefit in RCC. The review also explores the potential of circulating tumor DNA (ctDNA) as a biomarker for better therapy selection and patient stratification. It emphasizes the need for ongoing research to establish survival benefits and suggests integrating biomarkers and risk stratification to optimize adjuvant immunotherapy in BC and RCC.

Evaluation of the efficacy and safety of nivolumab in the second- or later-line treatment of patients with locally advanced/metastatic non-small cell lung cancer in Türkiye: a retrospective multicenter non-interventional registry study.

OBJECTIVE: To evaluate the efficacy and safety of nivolumab in the second-line (2L) or later-line (LL) treatment of patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) in real-life setting in Türkiye. METHODS: This study was designed as a national, multi-center, retrospective study. The study population was evaluated in two groups for the line of nivolumab therapy: those receiving nivolumab in the 2L (Group 2L) and third-line (3L) or LL (Group 3L/LL). Efficacy was evaluated based on one-year overall survival (OS) and progression-free survival (PFS). Safety was evaluated based on treatment-related adverse events (AEs) and nivolumab discontinuation rate. RESULTS: Of 244 patients, 52.9% were in Group 2L and 47.1% were in Group 3L/LL. Demographic and clinical characteristics did not differ between the groups. In Group 2L and Group 3L/LL, one-year OS and PFS rates were 60.8% and 61.4% (p = 0.592) and 31.2% and 21.3% (p = 0.078), respectively. The objective response rate (ORR) was 34.7% in Group 2L and 27.3% in Group 3L/LL (p = 0.262). The percentage of patients reporting at least one AE in Groups 2L and 3L/LL was 34.9% and 43.5%, respectively (p = 0.169). Fatigue was the most common (16.4%) treatment-related AE in each group. The groups were comparable regarding the AE frequency. Nivolumab was discontinued in 61 patients in Group 2L and 53 patients in Group 3L/LL, with the most common reason being disease progression (57.4% and 66.0%, respectively). CONCLUSION: Nivolumab is safe and effective in the 2L or 3L/LL treatment of locally advanced/metastatic NSCLC and associated with acceptable AEs in real-life setting.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (around 85% of all lung cancers). Patients with NSCLC are usually diagnosed at advanced or metastatic stages. When cancer cells spread to other areas from where they first formed, it is called metastatic cancer. Surgery may not be a treatment option for such patients. Currently, immunotherapeutic agents are used in the treatment of NSCLC. Nivolumab is one of the approved immunotherapeutic agents in the treatment of patients with metastatic NSCLC, who have failed after receiving chemotherapy. Our study explored the efficacy and safety of nivolumab in real-life setting in Türkiye. Nivolumab effectiveness was evaluated by overall survival (OS) and progression-free survival (PFS) rates. OS indicates the proportion of patients who are still alive at a given time after diagnosis or treatment initiation. PFS refers to "the length of time during and after cancer treatment that a person lives with the disease but does not get worse". In the present study, one-year OS for 244 patients who received nivolumab was 61.1% and one-year PFS was 26.4%. Nivolumab safety was evaluated based on the frequency of adverse events observed during nivolumab therapy. Of the patients 38.9% had at least one side effect, with fatigue being the most common (16.4%). Our results support the earlier studies and showed that nivolumab was a safe and effective agent and is associated with acceptable side effecrs.

Unveiling the Role of Human Papillomavirus in Urogenital Carcinogenesis a Comprehensive Review.

Human papillomavirus (HPV), an oncogenic DNA virus, is the most common sexually transmitted virus and significant public health concern globally. Despite the substantial prevalence of HPV infection among men, routine testing remains elusive due to the lack of approved HPV tests and the complexity of detection methods. Various studies have explored the link between HPV and genitourinary cancers, revealing different associations influenced by geographic variation, histological subtype and methodological differences. These findings underscore the importance of further research to elucidate the role of HPV in male urogenital cancers. This comprehensive review delves into the intricate relationship between HPV and male genitourinary cancers, shedding light on the virus's oncogenic mechanisms and its reported prevalence. A deeper understanding of HPV's implications for male health is essential for advancing public health initiatives and reducing the burden of urogenital cancers worldwide.

Accuracy and usability of artificial intelligence chatbot generated chemotherapy protocols.

Background: Medical practitioners are increasingly using artificial intelligence (AI) chatbots for easier and faster access to information. To our knowledge, the accuracy and availability of AI-generated chemotherapy protocols has not yet been studied. Methods: Nine simulated cancer patient cases were designed and AI chatbots, ChatGPT version 3.5 (OpenAI) and Bing (Microsoft), were used to generate chemotherapy protocols for each case. Results: Generated chemotherapy protocols were compared with the original protocols for nine simulated cancer patients. ChatGPT's overall performance was 5 out of 9 on protocol generation, and Bing's was 4 out of 9; this was statistically nonsignificant (p = 1). Conclusion: AI chatbots show both potential and limitations in generating chemotherapy protocols. The overall performance is low, and they should be used carefully in oncological practice.

Antibody Drug Conjugates in Urological Cancers: A Review of the Current Landscape.

PURPOSE OF REVIEW: Our review delves into the progress across urological malignancies and discusses ongoing challenges and future directions in antibody-drug conjugate (ADC) development, emphasising their transformative potential in cancer care. RECENT FINDINGS: ADCs have advanced from hematologic to solid tumours, notably in breast cancer, and are now pivotal in metastatic urological cancers as both monotherapies and in combination regimens, underscored by the FDA's approval of enfortumab vedotin and sacituzumab govitecan for metastatic urothelial cancer. Progress in metastatic prostate cancer, particularly with ADCs targeting PSMA and STEAP1, is noteworthy, although renal cell cancer presents ongoing challenges. There is a continual search for agents in the metastatic, relapsed testicular cancer landscape. ADCs have emerged as a pivotal innovation in oncology, blending targeted antibody therapy with potent cytotoxic drugs, significantly advancing treatment options for urological malignancies.

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.

Adrenocortical Cancer in the Real World: A Comprehensive Analysis of Clinical Features and Management from the Turkish Oncology Group (TOG).

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis. MATERIALS AND METHODS: A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan-Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses. RESULTS: The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses. CONCLUSION: ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions.

Effect of HER2/CEP17 ratio on survival in metastatic HER2-positive gastric cancer, multicenter study.

AIM: HER2-positive metastatic gastric cancer is still a highly fatal disease despite advances. We aimed to investigate the relationship between HER2/CEP17 ratio and survival in patients with HER2-positive metastatic gastric cancer. METHODS: A total of 99 patients from 8 different centers in Turkey were included in the study. Patients with HER2-positive metastatic gastric cancer and whose HER2/CEP17 ratio was examined were included in the study. Patients were divided into two groups according to HER2/CEP17 values, and survival analysis was performed. RESULTS: The median age was 64 (24-83) years. There were 74 (74.8%) male and 25 (25.2%) female patients. OS in the high HER2/CEP17 ratio group was 21.97 months (95% CI: 16.36-27.58), and in the low ratio group was 16.17 months (95% CI: 10.95-21.38) (p = 0.015). OS was 17.7 months (95% CI: 7.02-28.37) in the high HER2 gene copy number group and 10.13 months (5.55-14.71) in the group with low copy number (p = 0.03). PFS was 10.94 months (95% CI: 7.55-14.33) in the group with high HER2 gene copy number and 7.56 months (4.62-10.49) in the low copy number group (p = 0.06). CONCLUSION: Patients with both high HER2 gene amplification and high HER2/CEP17 ratio had better OS. The PFS of the group with high HER2 gene amplification was also better. To our knowledge, this is the first study in the literature showing that the HER2/CEP17 ratio affects survival in patients with metastatic gastric cancer.

Exploring the connection between microsatellite instability and inflammatory indicators in cancers.

Aim: This study aimed to investigate the association between microsatellite instability (MSI) status and inflammatory indicators in patients with cancer. Patients & methods: A total of 204 patients with various cancer diagnoses, including 102 with MSI-high (MSI-H) and 102 with microsatellite stable tumors, were enrolled. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein (CRP)-to-albumin ratio and systemic immune-inflammation index were evaluated. Results: In microsatellite stable patients, NLR, LMR, PLR and systemic immune-inflammation index were significantly linked to worse survival in univariate analysis, and having a LMR ≤2.6 negatively affected survival in multivariate analysis, although these indicators did not affect the survival of MSI-H patients. Conclusion: The impact of chronic inflammation on survival varies with MSI status. Further research is needed for targeted therapies in different tumors.

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.

Combination therapies in patients with favorable risk metastatic renal cell Carcinoma: A Systematic Review and Meta-Analysis.

INTRODUCTION: Immunotherapy (IO)-based combination therapies have emerged as the standard of care for first-line treatment of metastatic renal cell carcinoma (mRCC) among patients classified as intermediate and poor risk. However, in the favorable risk group, the available data remains less compelling. This study aims to assess and compare the effectiveness of IO-based combination therapies versus tyrosine kinase inhibitor (TKI) monotherapy in patients with favorable risk group according to the International mRCC Database Consortium (IMDC). METHODS: Recent update data from phase-III RCTs of IO-based combinations approved by the Food and Drug Administration were used. Studies that provided data on progression free survival (PFS) and overall survival (OS) of IMDC favorable risk were included in the analysis. RESULTS: A cohort of 1,088 patients categorized within the IMDC favorable risk group was enrolled for analysis. In comparison to sunitinib, the combination of immunotherapy (IO) and tyrosine kinase inhibitor (TKI) exhibited a reduction in the risk of disease progression (HR = 0.67, 95 % CI: 0.55-0.82; p < 0.001). Conversely, the combination of IO and IO displayed an elevated risk of disease progression (HR = 1.60, 95 % CI: 1.13-2.26; p = 0.008). However, neither the IO plus TKI (HR = 0.99, 95 % CI: 0.79-1.24; p = 0.92) nor IO plus IO (HR = 0.94, 95 % CI: 0.64-1.37; p = 0.75) combinations demonstrated a noteworthy improvement in overall survival (OS). Notably, within the IO plus TKI subgroup, combination therapy yielded a higher objective response rate (ORR) (OR = 0.40, 95 % CI: 0.28-0.57; p < 0.001). On the other hand, the IO plus IO combination displayed a lower ORR than sunitinib (OR = 2.54, 95 % CI: 1.51-4.27; p < 0.001). CONCLUSIONS: In the first-line treatment of IMDC favorable-risk mRCC, IO and TKI combinations show enhanced progression-free survival and response rate without improving overall survival. This emphasizes the demand for further exploration of combination therapies in this patient group.

Determining magnitude of benefit from poly(ADP-ribose) polymerase inhibitors in prostate cancer.

The treatment landscape for castration-resistant prostate cancer (mCRPC) is undergoing significant advancements, particularly with the emergence of poly(ADP-ribose) polymerase inhibitors and their recent US FDA authorizations. The combination of olaparib with abiraterone and prednisone/prednisolone has gained approval for mCRPC patients harboring confirmed BRCA mutations. Subsequently, talazoparib in combination with enzalutamide was approved for patients with mutations in homologous recombination repair genes. Nevertheless, emerging evidence suggests that these treatments may confer benefits irrespective of specific biomarkers. While the understanding of biomarkers in therapy selection for mCRPC is expanding, further data are warranted to provide comprehensive elucidation for guiding clinical practice.

The efficacy of immunotherapy and chemoimmunotherapy in patients with advanced rare tumors: A Turkish oncology group (TOG) study.

INTRODUCTION: The advances in immune checkpoint inhibitors (ICIs) were relatively slow in rare tumors. Therefore, we conducted a multi-center study evaluating the efficacy of ICI monotherapy and the combination of ICIs with chemotherapy (CT) in patients with advanced rare tumors. METHODS: In this retrospective cohort study, we included 93 patients treated with ICIs for NCI-defined rare tumors from the 12 cancer centers in Turkey. The primary endpoints were the overall response (ORR) and disease control rate (DCR). RESULTS: The cohort's median age was 56, and 53.8% of the patients were male. The most frequent diagnosis was sarcoma (29%), and 81.7% of the patients were previously treated with at least one line of systemic therapy in the advanced stage. The ORR and DCR were 36.8% and 63.2%, respectively. The germ cell tumors had the lowest ORR (0%), while the Merkel cell carcinoma had the highest ORR to ICIs (57.1%). Patients treated with ICI + ICI or ICI plus chemotherapy combinations had higher ORR (55.2% vs. 27.6%, p = 0.012) and DCR (82.8% vs. 53.4%, p = 0.008). The median OS was 13.47 (95% CI: 7.79-19.15) months, and the six and 12-month survival rates were 71% and 52%. The median duration of response was 16.59 months, and the 12-month progression-free survival rate was 66% in responders. The median time-to-treatment failure was 5.06 months (95% CI: 3.42-6.71). Three patients had high-grade irAEs with ICIs (grade 3 colitis, grade 3 gastritis, and grade 3 encephalitis in one patient each). CONCLUSION: We observed over 30% ORR and a 13-month median OS in patients with rare cancers treated with ICI monotherapy or ICI plus CT combinations. The response rates to ICIs or ICIs plus CT significantly varied across different tumor types. Responding patients had over 2 years of survival, highlighting a need for further trials with ICIs for patients with rare tumors.

Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma.

BACKGROUND: No new agent has improved overall survival in patients with unresectable or metastatic urothelial carcinoma when added to first-line cisplatin-based chemotherapy. METHODS: In this phase 3, multinational, open-label trial, we randomly assigned patients with previously untreated unresectable or metastatic urothelial carcinoma either to receive intravenous nivolumab (at a dose of 360 mg) plus gemcitabine-cisplatin (nivolumab combination) every 3 weeks for up to six cycles, followed by nivolumab (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine-cisplatin alone every 3 weeks for up to six cycles. The primary outcomes were overall and progression-free survival. The objective response and safety were exploratory outcomes. RESULTS: A total of 608 patients underwent randomization (304 to each group). At a median follow-up of 33.6 months, overall survival was longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for death, 0.78; 95% confidence interval [CI], 0.63 to 0.96; P = 0.02); the median survival was 21.7 months (95% CI, 18.6 to 26.4) as compared with 18.9 months (95% CI, 14.7 to 22.4), respectively. Progression-free survival was also longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for progression or death, 0.72; 95% CI, 0.59 to 0.88; P = 0.001). The median progression-free survival was 7.9 months and 7.6 months, respectively. At 12 months, progression-free survival was 34.2% and 21.8%, respectively. The overall objective response was 57.6% (complete response, 21.7%) with nivolumab-combination therapy and 43.1% (complete response, 11.8%) with gemcitabine-cisplatin alone. The median duration of complete response was 37.1 months with nivolumab-combination therapy and 13.2 months with gemcitabine-cisplatin alone. Grade 3 or higher adverse events occurred in 61.8% and 51.7% of the patients, respectively. CONCLUSIONS: Combination therapy with nivolumab plus gemcitabine-cisplatin resulted in significantly better outcomes in patients with previously untreated advanced urothelial carcinoma than gemcitabine-cisplatin alone. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 901 ClinicalTrials.gov number, NCT03036098.).

Efficacy of Capecitabine and Temozolomide Regimen in Neuroendocrine Tumors: Data From the Turkish Oncology Group.

INTRODUCTION: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs). METHODS: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey. RESULTS: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (P < .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment. CONCLUSIONS AND RELEVANCE: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET.

Adjuvant therapy for renal cell carcinoma: A systematic review of current landscape and future directions.

The advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has been transformative for the treatment of advanced renal cell carcinoma (RCC). Their efficacy post-surgical resection remains a contentious point. Various phase 3 RCTs have assessed their potency. Amongst evaluated agents, sunitinib and pembrolizumab have demonstrated notable disease-free survival benefits. Sunitinib's potential is diminished due to absence of clear overall survival (OS) benefits and side-effect profile. Pembrolizumab shows better tolerance, conclusive OS data are forthcoming. This scenario underscores the pressing need for advanced risk stratification methods and discovery of novel biomarkers. Existing strategies, largely pre-dating TKI and ICI therapeutic era, lack sufficient accuracy in predicting relapse-risk. Our review offers a comprehensive analysis of key phase 3 RCTs, focusing on TKIs, mTOR-inhibitors, and ICIs for adjuvant RCC treatment. The intent is to shed light on the intricate landscape of RCC treatment, guiding future research directions for optimizing patient outcomes.

Cancer-associated thrombosis and drug-drug interactions of antithrombotic and antineoplastic agents.

Venous thromboembolism (VTE) is often associated with malignant diseases and notably contributes to morbidity and mortality in patients with cancer. Cancer-associated thrombosis (CAT) brings additional costs to health expenditures and has a negative impact on oncological outcomes. Either the recurrence rate of VTE or bleeding complications are also higher in patients with cancer. Prophylactic anticoagulation has been recommended in peri-surgical periods, inpatient settings, and high-risk ambulatory patients. Although various risk stratification scores are used, none are ideal for identifying patients who can benefit from anticoagulant prophylaxis. New risk scoring systems or biomarkers are needed to identify patients who are more likely to benefit from prophylaxis with low bleeding risk. The questions about the patients who will be given prophylaxis and those who develop thromboembolism, with which drug, and how long they will be treated are still not fully answered. Anticoagulation is the cornerstone of the treatment, but management of CAT remains complex. Low molecular weight heparins and direct oral anticoagulants are effective and safe options for the treatment of CAT. Recognizing adverse effects, drug-drug interactions, and accompanying conditions that cause dose adjustment is crucial. Prevention and treatment of VTE in patients with cancer require a multidisciplinary and patient-based approach. PLAIN LANGUAGE SUMMARY: Cancer-associated thrombosis is a significant cause of mortality and morbidity in patients with cancer. Chemotherapy, surgery, and/or use of central venous access remarkably increase the risk of thrombosis. Prophylactic anticoagulation should be considered not only in inpatient follow-up and during peri-surgical period but also ambulatory patients with a high risk of thrombosis. Many parameters, such as drug-drug interactions, primary side of cancer, and comorbidities of patients should be considered when selecting anticoagulant drugs. More accurate risk stratification scores or biomarkers are still an unmet need.

Nivolumab-induced immune-related neutropenia in a renal cell carcinoma patient.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have considerably improved the prognosis of solid tumors. However, this class of medications can cause immune-related adverse events, which represent a distinct spectrum of adverse events in cancer treatment. CASE REPORT: Here we present a case of immune-related neutropenia (irN) that occurred in a 47-year-old man with metastatic clear cell renal cell carcinoma (ccRCC). During the 18 months of nivolumab monotherapy, severe neutropenia occurred. Buccal mucosal aphthous ulcers and antineutrophil cytoplasmic antibody positivity concurrently emerged with neutropenia. The patient was diagnosed with irN after a comprehensive evaluation ruled out all other likely causes. MANAGEMENT AND OUTCOME: Neutropenia improved with corticosteroids, but reoccurred with the introduction of nivolumab. During the approximately nine-month follow-up period after nivolumab treatment was permanently discontinued due to neutropenia, there was no disease progression. DISCUSSION: IrN associated with nivolumab treatment for metastatic ccRCC is uncommon. The pathophysiology of irN is not entirely understood. Corticosteroids are one of the most commonly used drugs for the treatment of irN. As ICIs become more widely used, medical oncologists will encounter this side effect more frequently.

Prognostic factors for regorafenib treatment in patients with refractory metastatic colorectal cancer: A real-life retrospective multi-center study.

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival.

Visceral Metastasis Predicts Response to New Hormonal Agents in Metastatic Castration-Sensitive Prostate Cancer.

Visceral metastasis (VM) and a higher number of bone metastasis generally define high volume/risk in patients with metastatic castration-sensitive prostate cancer (mCSPC). Subgroup analysis of pivotal trials did not show a clear benefit of second-generation non-steroidal anti-androgens (NSAAs) in patients with VM. However, subgroup analysis of the trial assessing abiraterone acetate, a CYP 17 inhibitor, plus prednisone (AAP) showed an improved overall survival (OS) in patients with mCSPC with VM. We searched MEDLINE, Web of Science, and congress abstracts for the phase III randomized controlled trials of second-generation NSAAs and AAP in patients with mCSPC. In this pooled analysis, we included 6485 patients from the 6 phase III trials. The rate of patients with VM was 15.2%. Interestingly, in contrast to NSAAs, AAP seems to be effective in improving OS among patients with VM (hazard ratio, HR: 0.89, 95% CI, 0.72-1.11, P = .30 for second-generation NSAAs; HR: 0.58, 95% CI, 0.40-0.84, P = .004 for AAP). In contrast, both second-generation NSAAs (HR: 0.63, 95% CI, 0.57-0.70, P < .001) and AAP (HR: 0.68, 95% CI, 0.57-0.81, P < .001) improved OS in patients without VM. In this pooled analysis, we demonstrate that while AAP provided an OS improvement in patients with VM, second-generation NSAAs did not demonstrate a similar OS benefit in this population.