Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study.

BACKGROUND: Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. PATIENTS AND METHODS: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors. RESULTS: In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1-2 or 3-4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001). CONCLUSIONS: Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy.

Real-world treatment outcomes from nationwide Onco-colon Turkey registry in RAS wild-type patients treated with biologics second-line mCRC.

BACKGROUNDS AND OBJECTIVES: Colorectal cancer is one of the leading causes of mortality both globally and in our country. In Turkey, we conducted a multicenter investigation into the effectiveness of second-line treatments and real-life data for patients with RAS wild-type metastatic colorectal cancer (NCT04757311). MATERIALS AND METHODS: In this retrospective analysis, records from 28 centers were collected, and histopathological, molecular, and clinical characteristics were documented. Patients were categorized into groups based on their second-line biological treatments: anti-EGFR (Group A and Group B, panitumumab and cetuximab) and anti-VEGF (Group C, bevacizumab and aflibercept). They were then compared within these groups. RESULTS: A total of 588 patients with documented RAS wild-type status were evaluated. The median OS was 15.7, 14.3 and 14.7 months in Group A, Group B and Group C, respectively (p = 0.764). The median PFS of the patients in second-line setting that received panitumumab, cetuximab and bevacizumab/aflibercept were 7.8, 6.6 and 7.4 months, respectively (p = 0.848). CONCLUSION: According to the results of our real-life data study, there is no significant difference in efficiency between the combination of biological agent and chemotherapy used in the second-line treatments.

Real-world effectiveness of pembrolizumab as first-line therapy for cisplatin-ineligible patients with advanced urothelial carcinoma: the ARON-2 study.

BACKGROUND: The advent of immune-checkpoint inhibitors has challenged previous treatment paradigms for advanced urothelial carcinoma (UC) in the post-platinum setting as well as in the first-line setting for cisplatin-ineligible patients. In this study, we investigated the effectiveness of pembrolizumab as first-line treatment for cisplatin-ineligible UC. METHODS: Data from patients aged ≥ 18 years with cisplatin-ineligible UC and receiving first-line pembrolizumab from January 1st 2017 to September 1st 2022 were collected. Cisplatin ineligibility was defined according to the Galsky criteria. Thirty-three Institutions from 18 countries were involved in the ARON-2 study. RESULTS: Our analysis included 162 patients. The median follow-up time was 18.9 months (95%CI 15.3-76.9). In the overall study population, the median OS was 15.8 months (95%CI 11.3-32.4). The median OS was significantly longer in males versus females while no statistically significant differences were observed between patients aged < 65y versus ≥ 65y and between smokers and non-smokers. According to Recist 1.1 criteria, 26 patients (16%) experienced CR, 32 (20%) PR, 39 (24%) SD and 55 (34%) PD. CONCLUSIONS: Our data confirm the role of pembrolizumab as first-line therapy for cisplatin-unfit patients. Further studies investigating the biological and immunological characteristics of UC patients are warranted in order to optimize the outcome of patients receiving immunotherapy in this setting.

Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study.

BACKGROUND: Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab. METHODS: We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model. RESULTS: A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival. CONCLUSIONS: Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.

Prognostic importance of SUVmax values evaluated by 18F-FDG-PET/CT before nivolumab treatment in patients with metastatic renal cell carcinoma.

BACKGROUND: Nivolumab is a monoclonal antibody that binds to the programmed death-1 (PD-1) receptor and blocks its interaction with PD-L1 and PD-L2. High response rates have been achieved with its use in the treatment of metastatic renal cell carcinoma (mRCC). We aimed to determine a relationship between 18-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography (18F-FDG-PET/CT) performed before nivolumab treatment and treatment-related survival. METHODS: Between 2014 and 2021, 32 patients who received nivolumab and had pre-treatment 18F-FDG-PET/CT evaluation were included in this retrospective study. The total SUVmax (sum of SUVmax) of all tumoral foci and the lesion with the highest SUVmax value were recorded. The relationship of these values with progression-free survival (PFS) and overall survival (OS) was evaluated. RESULTS: The median highest SUVmax and sum of SUVmax values were found as 14.4 and 41.4, respectively. PFS and OS were longer in the group with a sum of SUVmax value below 41.4 compared to the group with a higher group (OS, median 9.52 vs. 4.2 months [P=0.018]; PFS, median 9.6 vs. 3 months [P=0.003], respectively). In the group with the highest SUVmax value below 14.4, PFS was evaluated as statistically significant compared to the higher group (PFS, median 16.74 vs. 3.3 months [P=0.004]), while OS was not found to be statistically significant (OS, median 25.45 vs. 16.74 months (P=0.110)). CONCLUSIONS: Our study showed that there might be a relationship between SUVmax values and PFS and OS. The SUVmax values before nivolumab treatment can be used to predict prognosis and survival in mRCC patients.

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.

Real-Life Analysis of Efficacy and Safety of Everolimus Plus Exemestane in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Patients: A Turkish Oncology Group (TOG) Study.

PURPOSE: This study evaluated the efficacy and safety of everolimus (EVE) plus exemestane (EXE) in hormone-receptor positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) patients in real-life settings. METHODS: Overall, 204 HR+, HER2- MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included. Overall survival (OS) and progression-free survival (PFS) and safety data were analyzed. RESULTS: The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively. Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response (p = 0.035) and PFS (p = 0.024). The presence of bone-only metastasis was associated with better treatment response (p = 0.002), PFS (p < 0.001), and OS (p = 0.001). CONCLUSION: We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER - MBC patients.

Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, ALK-positive non-small-cell lung cancer patients: a Turkish Oncology Group study.

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.

The advancements in cancer treatment, particularly in the last two decades, have been promising. Non-small-cell lung cancer (NSCLC) is one of the most important diseases experiencing these promising developments. ALK positivity, which is caused by the rearrangement of different gene fragments between two chromosomes, affects about 5% of NSCLC patients. This provides a target for next-generation therapies. One of these targeted therapy drugs is alectinib. The authors examined the outcomes of 271 patients with body-disseminated NSCLC who received alectinib as initial targeted therapy. These patients were not chosen to participate in a clinical phase study. They were treated with an approved drug; the study also included 97 patients who had previously received chemotherapy. The median duration of survival without disease worsening was 26 months for all patients receiving alectinib treatment. This value was 28.8 months in 177 patients who had not received any treatment before alectinib. Regardless of disease status, 77% of all patients were found to be alive at the end of the first year. Alectinib treatment resulted in a significant improvement of the disease in approximately four out of five patients. The treatment's side effects were generally tolerable or manageable. Only four patients were reported to have discontinued their medication due to treatment-related side effects. These real-world findings are compatible with previous clinical research. Alectinib is an important first-line treatment option for patients with advanced, ALK-positive NSCLC.

Response to first-line chemotherapy regimen is associated with efficacy of immune checkpoint blockade therapies in patients with metastatic urothelial carcinoma.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity in previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important. PATIENTS AND METHODS: In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher's exact test. Median follow-up was calculated using the reverse Kaplan-Meier method. OS was estimated by using the Kaplan-Meier method. RESULTS: The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with ATZ (p = 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (p = 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases {Hazard ratio [HR] = 1.9; p = 0.04}, ECOG PS ≥ 1 (HR = 2.7; p = 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8; p < 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39; p < 0.001) maintained a significant association with OS in multivariate analysis. CONCLUSIONS: Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients' use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.

Multidrug refractory aggressive metastatic TFE3 (+) renal cell carcinoma: A case report.

BACKGROUND: Transcription factor E3 (TFE3) related renal cell carcinomas constitute a very small percent of all renal tumors in adults. Prognosis mainly depends on the stage of the disease at the time of diagnosis which is often poor. There is yet to be a standardized treatment protocol. Treatment options include agents identical to TFE3(-) cell renal carcinoma treatment. We present a case of a young woman with a rapidly progressing metastatic TFE3 (+) renal cell carcinoma. CASE REPORT: A 31 year old female presented with abdominal mass, distension, nausea. Initial tests and tumor markers found to be normal. Abdominal CT scan revealed a left retroperitoneal mass along with three other neighboring masses in liver manifesting as metastases. Trucut biopsy and immunohistochemical staining confirmed the retroperitoneal mass as TFE3 (+) renal cell carcinoma.Management and outcome: Sunitinib, pazopanib, nivolumab, axitinib treatments are consecutively given after surgery. It is noteworthy that rapid progression was observed under nivolumab treatment. DISCUSSION: During surveillance, rapid progression is noted under consecutive immunotherapy which was unexpected. Thus, there is a need for more standardized treatment protocols and invention of new agents for management of TFE3 (+) renal cell carcinoma.

Nivolumab in metastatic renal cell carcinoma: results from the Turkish Oncology Group Kidney Cancer Consortium database.

Aim: The authors present real-world data on the efficacy and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Methods: The Turkish Oncology Group Kidney Cancer Consortium (TKCC) database includes patients with mRCC from 13 cancer centers in Turkey. Patients with mRCC treated with nivolumab in the second line and beyond were extracted from the TKCC database. Results: A total of 173 patients were included. The rates of patients treated with nivolumab in the second, third, fourth and fifth lines were 47.4%, 32.4%, 14.5% and 5.7%, respectively. The median overall survival and progression-free survival were 24.2 months and 9.6 months, respectively. Nivolumab was discontinued owing to adverse events in 11 (6.4%) patients. Conclusion: Nivolumab was effective in patients with mRCC and no new safety signal was observed.

Lay abstract Nivolumab is an immune checkpoint inhibitor (ICI) that blocks the communication between T cells and cancer cells and instead activates T cells to fight against cancer. Metastatic renal cell carcinoma (mRCC) is one of the most susceptible tumors to ICIs. The Checkmate 025 trial showed the efficacy of nivolumab in patients with previously treated mRCC. In this real-world study, 173 patients with mRCC were treated with nivolumab in the second line and beyond. Nivolumab was effective in the real-world setting without additional safety concerns.

The mortality rate of COVID-19 was high in cancer patients: a retrospective single-center study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has quickly turned into a global pandemic with close to 5 million cases and more than 320,000 deaths. Cancer patients constitute a group that is expected to be at risk and poor prognosis in COVID pandemic. We aimed to investigate how cancer patients are affected by COVID-19 infection, its clinical course and the factors affecting mortality. METHODS: In our single-center retrospective study, we included cancer patients with laboratory confirmed COVID-19 in our hospital. Demographic, clinical, treatment, and laboratory data were obtained from electronic medical records. Logistic regression methods were used to investigate risk factors associated with in-hospital death. RESULTS: In the hospital, 4489 patients were hospitalized with COVID infection and 77 were cancer patients. The mean age of cancer patients was 61.9 ± 10.9 and 44 of them were male (62%). While the mortality rate in non-cancer patients was 1.51% (n = 68), this rate was significantly higher in cancer patients, 23.9% (n = 17). The stage of the disease, receiving chemotherapy in the last 30 days also lymphopenia, elevated troponin I, D-dimer, CRP, and CT findings were associated with severe disease and mortality. Severe lung involvement (OR = 22.9, p = 0.01) and lymphopenia (OR = 0.99, p = 0.04) are the most important factors influencing survival in logistic regression. CONCLUSIONS: The disease is more severe in cancer patients and mortality is significantly higher than non-cancer patients. These data show that it may be beneficial to develop dynamic prevention, early diagnosis and treatment strategies for this vulnerable group of patients who are affected by the infection so much.

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. PATIENTS AND METHODS: In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. RESULTS: The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. CONCLUSIONS: This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.

Ribociclib induced acute kidney injury: A case report.

INTRODUCTION: Among females, breast cancer is the most common type of cancer. Hormon receptor positive (HR+) subtype constitutes 75% of the diagnosed breast cancers. Combination of the cyclin D-cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and endocrine therapy significantly improves overall survival and progression-free survival. Ribociclib is an oral CDK 4/6 inhibitor and some adverse effects are identified. According to MONALEESA 2-3-7 studies, no adverse effect (AE) were reported due to grade 3 or 4 acute kidney injury (AKI) that caused treatment discontinuation. CASE REPORT: We report a ribociclib-induced grade 3 AKI in an elderly woman who was treated for metastatic breast cancer. During first cycle of therapy, she was admitted to the oncology clinic with diagnosis of AKI.Management and outcome: Ribociclib treatment was discontinued and secondary causes of AKI were excluded. During the follow-up, kidney function values returned to the normal range spontaneously. Ribociclib treatment was re-initiated by reducing the dose (400 mg daily). Despite dose reduction; grade 3 AKI recurred when ribociclib was re-initiated and the drug was permanently discontinued. DISCUSSION: According to MONALEESA 2-3-7 studies; no AE were reported due to grade 3 or 4 AKI. Despite these studies, the FDA reported that 20% of patients with ribociclib + letrozole combination therapy may have any stage elevation of creatinine. Ribociclib induced creatinine elevations are generally mild (grade 1-2) and can be managed by dose reduction or close monitoring of creatinine levels. We report the first case of grade 3 AKI that caused treatment discontinuation following administration of ribociclib.

Is the duration of castration resistance predictive for sequential treatment responses in the metastatic castration-resistant prostate cancer setting?

OBJECTIVE: Prostate cancer is the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been the primary therapeutic approach for treatment of prostate cancer. However,nearly all patients develop the castration-resistant disease . We evaluated real-world data with abiraterone and enzalutamide treatment. By this data, we aimed to analyze whether that prior short response to ADT could predict response to subsequent therapy with androgen receptor axis targeted agent (ARATA). MATERIAL AND METHOD: We collected data from two cancer centers, 151 consecutive patients with treated abiraterone or enzalutamide in the first line of metastatic castration resistant prostat cancer (mCRPC) setting were included. The patients who received docetaxel in castration naive setting is also included. Time to castration resistance (TTCR) was defined as the duration from the initial to failure of primary ADT. RESULTS: Patients with treated ARATA were divided into two groups according to the time to castration resistance (TTCR). Patients who became resistant to ADT up to one year had a median PFS of 6.6 months, compared to median PFS of 13.3 months for patients who responded ADT for more than 1 year. (p = 0.002). In the post-docetaxel setting, median PFS is 12.6 months of patients with treated ARATA who had TTCR for more than one year, and median PFS is 6.6 months in those who had TTCR less than one year (p = 0.007).Univariate and multivariate analyses were performed to determine the clinical factors on ARATA outcomes. Eastern Cooperative Oncology Group (ECOG) performance status(PS), median prostate-specific antigen(PSA) and time to CRPC were significantly predicted outcomes of ARATA on multivariate analysis. CONCLUSION: TTCR is also a predictor for PFS of the patients who were treated ARATA both whole cohort and post-docetaxel.

Safe use of nivolumab in a patient with renal cell carcinoma and hepatitis B.

INTRODUCTION: Immunotherapy with checkpoint inhibitors gains a major role in bladder cancer. Because of the treatment's immune modulatory effects, patients may develop hepatitis. Hepatitis B was an exclusion criterion in clinical trials that investigated nivolumab. Therefore, its effects and risk of hepatitis B reactivation in nivolumab are not clinically investigated in renal cell carcinoma patients with hepatitis B. CASE REPORT: In this case report, we presented a metastatic renal cell carcinoma patient who was treated with anti-viral treatment for hepatitis reactivation caused by previous sunitinib therapy. After progression, nivolumab was commenced and the patient was closely monitored with hepatic function tests. MANAGEMENT AND OUTCOME: Nivolumab was well tolerated and no treatment-related adverse effect occurred. Hepatitis or viral hepatitis reactivation was not detected. DISCUSSION: This case supports the safety of nivolumab in patients with renal cell carcinoma and viral hepatitis.

Elevation in serum uric acid levels predicts favourable response to erlotinib treatment in patients with metastatic non-small-cell lung cancer.

WHAT IS KNOWN AND OBJECTIVE: Erlotinib is a small molecule tyrosine kinase inhibitor which blocks the activation of epidermal growth factor receptor (EGFR), a transmembrane receptor that is upregulated in many cancer types. Inhibition of angiogenesis with consequent impairments in intratumoral microcirculation is one of the mechanisms through which EGFR inhibition halts the progression of cancer. A consequence of impaired microcirculation is intratumoral hypoxia, which results in increases in serum uric acid levels. The goal of this study was to investigate the relationship between serum uric acid levels and response to erlotinib in metastatic non-small-cell lung cancer (NSCLC). METHODS: A total of 56 patients with metastatic non-small-cell lung cancer who received erlotinib for a duration of at least 3 months were included in this retrospective cohort study. Demographic characteristics, progression status, baseline serum uric levels and 3-month serum uric acid levels were recorded and analysed. RESULTS AND DISCUSSION: Of the study population, 21 (37.5%) were female and 35 (62.5%) were male patients. No significant difference in above demographic characteristics was observed among exitus, survivor with progression and survivor without progression groups. Patients who responded favourably to erlotinib with no progression of their disease had significantly increased uric acid levels at 3-month follow-up (P = .01). Such a correlation was not observed if the patient was exitus (P = .47) or had progressed on erlotinib therapy (P = .19). WHAT IS NEW AND CONCLUSION: In conclusion, this study is the first to demonstrate significant increases in serum uric acid levels in patients with metastatic NSCLC who responded favourably to erlotinib and had no progression under erlotinib therapy. Further studies are required to confirm and characterize serum uric acid as a novel biomarker in predicting the outcome in those with metastatic NSCLC.

Long-lasting response with polycythemia to third-line axitinib treatment in metastatic renal cell carcinoma: Very rare case presentation.

INTRODUCTION: Clear cell renal cell carcinoma is characterized by mutation or inactivation of Von Hippel-Lindau suppressor gene. The mutation of Von Hippel-Lindau mechanism is associated with the upregulation of the hypoxia-inducible factor protein, inducing the overexpression of proteins including erythropoietin and vascular endothelial growth factor. Vascular endothelial growth factor receptor-targeted tyrosine kinase inhibitors are widely used in treatment of metastatic renal cell carcinoma. In paradoxical hematological effect with tyrosine kinase inhibitor therapies, hemoglobin level may be increased, but polycythemia requiring phlebotomy is very rare. CASE DESCRIPTION: We present here a case of renal cell carcinoma who received successive treatment with sunitinib, everolimus, and axitinib. While he had a normal hemoglobin level with prior sunitinib treatment, on the sixth week of axitinib treatment, he developed polycythemia and treatment response was seen after axitinib-associated polycythemia. CONCLUSION: Progression-free survival (PFS) was 30 months in our case with third-line treatment axitinib. Higher hemoglobin levels may be associated with longer survival. Polycythemia was the first response to treatment of axitinib in our patient. It may be an indicator of persistent treatment response.

Hepatitis B Reactivation Rate Is Higher Undergoing Some Cytotoxic Chemotherapy in Patients with Solid Tumors: A Large Retrospective Study.

OBJECTIVE: The reactivation rate of chronic hepatitis B virus infection in cancer patients and chemotherapy regimens thought to be associated with hepatitis reactivation were investigated. PATIENTS AND METHODS: In all, 3,890 cancer patients were included in this study. Mortality rates, chemotherapy regimens, cancer types, number of positive hepatitis serology and reactivation rates were obtained. RESULTS: Only 354 patients had positive hepatitis serology results (HBsAg+). Twenty-four patients (6.7%) with HBsAg positive serology had reactivation. In patients with hepatitis reactivation, the rates of usage of 5-fluorouracil (5-FU), cisplatin, cyclophosphamide, doxorubicin, steroid, rituximab, and vincristine were found to be significantly higher than corresponding rates in patients with positive hepatitis serology results but without hepatitis reactivation (p < 0.05 for all). CONCLUSION: Increased reactivation rates were detected with usage of 5-FU, cisplatin, cyclophosphamide, doxorubicin, steroid, rituximab, and vincristine.