Background The objective of this study is to describe the use of targeted therapies for the treatment of advanced renal cell carcinoma (RCC) and overall survival (OS) among patients in clinical practice in the Veterans Health Administration (VHA). Methods A retrospective cohort of 286 patients from 24 VHA Medical Centers diagnosed with advanced clear cell RCC between Fiscal Year (FY) 2010 and FY2014 was followed through September 30, 2016. Among patients who received targeted therapy, we described the medications taken, duration of therapy, and overall survival. We also assessed the effect of the first therapy received on overall survival using Cox Proportional Hazards models. Results There were 66 patients who did not receive therapy for their advanced RCC. Of the 220 treated patients, the mean (sd) number of medications received was 1.9 (1.1). The medications most commonly used first were sunitinib (61.8%), pazopanib (17.3%), and temsirolimus (10.9%). The median duration of first‐line therapy was 86 days (interquartile range [IQR] 42, 210). Median total duration of therapy was 159 days (IQR 58, 397). 62.3% of patients had ≥ 1 dose of therapy held or reduced, mainly due to an adverse drug event (ADE). Median survival from the start of treatment to death was 1.08 years (IQR 0.80, 1.31). Finally, receipt of temsirolimus vs sunitinib (HR 1.95 [95%CI 1.09,3.47]) as the first targeted therapy was independently associated with an increased hazard of death. Conclusion Our analysis of targeted therapies for advanced RCC in VHA suggests duration of treatment is shorter in a real‐world setting than in clinical trials, and dose reductions and ADEs are more common.

Purpose Nivolumab is a fully human IgG4 programmed death 1 immune checkpoint inhibitor (ICI) antibody that has anti-tumor activity by selectively blocking the interaction of the programmed death 1 receptor with its two known programmed death ligands PD-L1 and PD-L2. In doing so, this immune checkpoint inhibitor removes the negative signal stifling T cell activation and proliferation within the tumor microenvironment and demonstrates favorable antitumor activity. Case report We report an interesting case of immune checkpoint inhibitor-induced primary hypothyroidism with associated hypothyroid myopathy in a young patient with surgically resected stage IIIB melanoma receiving adjuvant nivolumab. He presented 12 weeks into therapy with severe myalgias, arthralgias, and intermittent disequilibrium of unclear etiology. Laboratory evaluation demonstrated a significant elevation in thyroid stimulating hormone and creatine kinase with an undetectable free T4 with standard laboratory measurement. With thyroid hormone replacement therapy alone, he had rapid improvement in his musculoskeletal symptoms and laboratory parameters over a three-week period. Discussion This case emphasizes the serious nature of endocrine immune-related adverse events in patients receiving immune checkpoint inhibitors. Additionally, it highlights that unlike most other immune-related adverse events, endocrine immune-related adverse events can generally be managed with adequate hormone replacement alone with swift improvements in symptoms. This allows patients to continue immune checkpoint inhibitors safely without immunosuppression which may dampen the anti-tumor activity of these agents. Conclusion This case highlights the importance of early recognition and the appropriate management of endocrine immune-related adverse events to maximize patient safety and good outcomes.

Background: The bone health of patients with locally advanced and metastatic prostate cancer is at risk from treatment-related bone density loss and skeletal-related events from metastatic disease in bones. Evidence-based guidelines recommend using denosumab or zoledronic acid at bone metastasis-indicated dosages in the setting of castration-resistant prostate cancer with bone metastases and at the osteoporosis-indicated dosages in the hormone-sensitive setting in patients with a significant risk of fragility fracture. For the concerns of jaw osteonecrosis, a dental evaluation is recommended before starting bone-modifying agents. The literature review suggests a limited evidence-based practice for bone health with prostate cancer in the real world. Both under-treatment and inappropriate dosing of bone remodeling therapies place additional risks to bone health. An incomplete dental work up before starting bone-modifying agents increases the risk of jaw osteonecrosis. Methods: We created an algorithm-based clinical practice tool to minimize the deviation from evidence-based guidelines at our center and provide appropriate bone health care to our patients by ensuring indication-appropriate dosing and dental screening rates. This order set was incorporated into the electronic medical record system for ordering a bone remodeling agent for prostate cancer. The tool prompts the clinicians to follow the appropriate algorithm in a stepwise manner to ensure a pretreatment dental evaluation and use of the correct dosage of drugs. Results: We analyzed the data from Sept 2019 to April 2022 following the incorporation of this tool. 0/35 (0%) patients were placed on inappropriate bone modifying agent dosing, and dental health was addressed in every patient before initiating treatment. We compared the change in the practice of prescribing and noted a significant difference in the clinician’s practice while prescribing denosumab/zoledronic acid before and after implementation of this tool [incorrect dosing: 24/41 vs. 0/35 (p < 0.00001)]; and an improvement in pretreatment dental checkup before and after implementation of the tool was noted to be [missed dental evaluation:12/41 vs. 0/35 (p < 0.00001)]. Conclusion: We found that incorporating an evidence-based algorithm in the order set while prescribing bone remodeling agents significantly improved our institutional clinical practice of indication-appropriate dosing and dental screening rates, and facilitated high-quality, evidence-based care to our patients with prostate cancer.

Patients may present with multiple malignancies in the setting of particular environmental and occupational exposures. These patients often require combination systemic therapy, which has not yet been studied for concurrent use. While toxicities for specific chemotherapies and immunotherapies may be well known, the possibility of exaggerated toxicity due to combination therapy exists and is understudied. Several trials are underway that may shed further light on how combination therapies affect patient toxicity. This case report outlines the unfortunate development of severe edema and rash, refractory to traditional methods of management, from combining immunotherapy and chemotherapy.