Can Cytoreductive Nephrectomy Improve Outcomes of Nivolumab Treatment in Patients with Metastatic Clear-Cell Renal Carcinoma?

Background: This study aimed to investigate the effect of cytoreductive nephrectomy (CN) on the survival outcomes of nivolumab used as a subsequent therapy after the failure of at least one anti-vascular endothelial growth factor (VEGF) agent in patients with metastatic clear-cell renal-cell carcinoma (ccRCC). Methods: We included 106 de novo metastatic ccRCC patients who received nivolumab after progression on at least one anti-VEGF agent. Multivariate Cox regression analysis was performed to investigate the factors affecting survival in patients receiving nivolumab. Results: Of the 106 de novo metastatic ccRCC patients, 83 (78.3%) underwent CN. There were no statistical differences between the two groups in terms of age, gender, Eastern Cooperative Oncology Group (ECOG) score, tumor size, International Metastatic RCC Database Consortium (IMDC) risk group, number of previous treatment lines, first-line anti-VEGF therapy, or metastasis sites (p = 0.137, p = 0.608, p = 0.100, p = 0.376, p = 0.185, p = 0.776, p = 0.350, and p = 0.608, respectively). The patients who received nivolumab with CN had a longer time to treatment discontinuation (TTD) [14.5 months, 95% confidence interval (CI): 8.6-20.3] than did those without CN 6.7 months (95% CI: 3.9-9.5) (p = 0.001). The median overall survival (OS) was 22.7 months (95% CI: 16.1-29.4). The patients with CN had a median OS of 22.9 months (95% CI: 16.3-29.4), while those without CN had a median OS of 8.1 months (95% CI: 5.6-10.5) (p = 0.104). In the multivariate analysis, CN [hazard ratio (HR): 0.521; 95% CI: 0.297-0.916; p = 0.024] and the IMDC risk score (p = 0.011) were statistically significant factors affecting TTD; however, the IMDC risk score (p = 0.006) was the only significant factor for overall survival. Conclusions: Our study showed that the TTD of nivolumab was longer in metastatic ccRCC patients who underwent cytoreductive nephrectomy.

Decrease in estimated glomerular filtration rates in non-small cell lung cancer patients treated with crizotinib.

Introduction: Crizotinib is a tyrosine kinase inhibitor used in patients with non-small cell lung cancer, and there are uncertainties about its effect on kidney function. In this study, it was aimed to document the possible adverse effect of the drug on kidney functions. Materials and Methods: The estimated glomerular filtration rates (eGFRs) of the patients were calculated by creatinine-based Chronic Kidney Disease Epidemiology Collaboration and compared by months using the paired samples t-test. Kaplan-Meier survival method was used for progression-free survival and overall survival (OS) analysis. Results: Twenty-six patients who received crizotinib were included in the study, and the median progression-free survival time with crizotinib was 14.2 months and the median OS time was 27.4 months. There was a significant reduction of eGFR after the 1st month of crizotinib treatment when compared to the rate before treatment initiation (P < 0.001). The eGFR values at the end of the 1st month and the 2nd month of treatment and the 2nd and 3rd months of treatment were statistically similar (P = 0.086, P = 0.663; respectively). This decrease in eGFR values was reversible, and there was no difference detected between pretreatment and posttreatment discontinuation (P = 0.100). Conclusion: A reversible decrease in renal functions was detected in patients using crizotinib. When the literature data are examined, it is thought that the reason for this decrease may be related to the increase in renal inflammation or a pseudo decrease due to the decrease in creatinine excretion. When evaluating renal functions in these patients, using noncreatine-based (iothalamate, etc.) calculations can give more accurate results.

Nivolumab induced hypophysitis in an advanced RCC patient.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are being commonly used to treat solid tumours such as renal cell carcinoma. Hypophysitis is an acute or chronic inflammation of the pituitary gland and nivolumab or pembrolizumab induced hypophysitis is markedly lower compared to ipilimumab. CASE REPORT: We present a novel case of a patient with mRCC who was diagnosed with nivolumab induced hypophysitis based on clinical suspicion due to his hormonal profile and a range of symptoms that he developed during nivolumab immunotherapy. MANAGEMENT AND OUTCOME: He was treated with high dose of hydrocortisone administered intravenously, subsequently changed to the oral route and physiologic dose. DISCUSSION: Nivolumab induced hypophysitis is a rare condition that usually presents with fewer symptoms. High degree of clinical suspicion and a multidisciplinary team required to diagnose and treat such cases.

Crizotinib for c-MET-amplified advanced NSCLC: a single-center experience.

INTRODUCTION: Lung cancer is the most common cause of cancer-related death in the world. Changes in the treatment of metastatic lung cancer in recent years have made targetable mutations gain importance. MET alteration is one of these driver mutations and crizotinib is a tyrosine kinase inhibitor used in therapy. METHODS: In our study, data of patients with c-MET amplification who received crizotinib treatment between July 2017 and November 2020 in the Medical Oncology Clinic of Bakirköy Dr. Sadi Konuk Training and Research Hospital were retrospectively analyzed. c-MET scanning was performed by the fluorescent in situ hybridization method by using Cytotest MET/CCP7 probe kit by evaluating 100 tumor cells and the threshold value for positivity was accepted as above 20%. RESULTS: Eight of 28 patients who received crizotinib treatment had c-MET amplification. Seven of these patients were male and one was female. Progression-free survival and overall survival in these eight patients were 9.4 and 10.9 months, respectively, and objective response rate was 50%. Grade 4 nausea was observed in only one patient; there was no grade 4-5 toxicity and no patient discontinued the drug due to toxicity. CONCLUSION: Crizotinib is an effective treatment option other than cytotoxic chemotherapy in the limited number of patients with MET amplification in the stage 4 lung adenocarcinoma subgroup. It is important to investigate this amplification, which can be detected especially in smoking patients in the appropriate patient group, and to use appropriate tyrosine kinase inhibitors in treatment.

Breast cancer in young and very young women; Is age related to outcome?

BACKGROUND: Breast cancer in young women is associated with aggressive biology. We analyzed histopathological and clinical properties of breast cancer patients diagnosed at ≤40 years of age. METHODS: Breast cancer patients who were admitted between 2015 and 2019 were included. Baseline characteristics of the patients with treatment-related outcomes were assessed. The study group was divided into two subgroups; <35 years old as "very young" and ≥35 years old as "young." RESULTS: The data of 137 patients (60 patients <35 years) were reviewed. The mean age was 34.7 years. The mean follow-up duration was 44.45 ± 26.39 months, and the mean disease-free survival was 36.17 ± 21.97 months. 11.4% of the patients were diagnosed with Stage 4 disease. Pathologic subtype was invasive ductal carcinoma in 86% of patients. 16.8% of the patients were luminal A, 38.7% luminal B, 30.5% were human epidermal growth factor receptor-2-positive type, and 15.3% were triple-negative. Only 5 (3.3%) patients had given birth after chemotherapy. During the follow-up period of early-staged diagnosed patients, metastatic disease occurred in 24.6%. The rate of distant metastasis development was statistically higher in the very young group (31% vs. 11%; P = 0.004). Thirteen patients (10.7%) died due to disease progression. Thirty-seven percent of the patients had a positive family history for either breast or ovarian cancer. CONCLUSIONS: Very young breast cancer patients seem to have a more aggressive disease course. The low rate of childbearing in this young patient population is conspicuous. An interdisciplinary approach for the management of this special patient population should be taken into consideration.

Thirty-day mortality rates after immunotherapy initiation.

Background: The aim of this study was to determine the cause of death in patients who died within 30 days after the first dose of immunotherapy. Methods: The data of 1432 patients treated with immunotherapy in six tertiary referral hospitals were retrospectively analyzed. Results: It was determined that 34 (2%) of the patients died within 30 days after the first dose of immunotherapy. Death occurred in all patients who received palliative therapy, and most patients (88%) received immunotherapy as second- or subsequent-line of therapy. The most common cause of death was disease progression and thromboembolic events. Conclusion: Preliminary results of the current study might give some clues to define the patient population in whom the fatal side effects of immunotherapy might be encountered.

Nivolumab for metastatic uveal melanoma: a multicenter, retrospective study.

Systemic treatment options with proven efficacy for the treatment of metastatic uveal melanoma are limited. In this study, we aimed to evaluate the efficacy of nivolumab in metastatic uveal melanoma patients. In our multi-center study, the files of patients who received nivolumab treatment with a diagnosis of metastatic uveal melanoma were retrospectively reviewed and their information was recorded. Seventeen patients were enrolledand 16 patients were evaluable for efficacy. The objective response rate (ORR) was 18% including one confirmed complete response and two confirmed partial responses. The median progression-free survival (PFS) was 5.8 months (95% CI, 0.03-11.57 months), and the median overall survival (OS) was 10.5 months (95% CI, 3.87-14.14 months). Significant longer OS and PFS were observed in patients with the performance status of the Eastern Cooperative Oncology Group (ECOG-PS) 0. Although significant longer OS was detected in patients with low median lactate dehydrogenase (LDH) levels, no significant difference was found in PFS. Grade 1 and 2 fatigue and decreased appetite were the most common side effects associated with treatment (17%); grade 3 and 4 side effects were not observed. Immunotherapy is also emerging as a treatment option among the limited number of treatment options in metastatic uveal melanoma (mUM), but its efficacy needs to be demonstrated with prospective studies involving a larger number of patients.

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.