PURPOSE We assessed the safety and efficacy of cabozantinib and nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignances. PATIENTS AND METHODS Patients received escalating doses of CaboNivo or CaboNivoIpi. The primary objective was to establish a recommended phase II dose (RP2D). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), duration of response (DoR), and overall survival (OS). RESULTS Fifty-four patients were enrolled at eight dose levels with a median follow-up time of 44.6 months; data cutoff was January 20, 2020. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 75% and 87% of patients treated with CaboNivo and CaboNivoIpi, respectively, and included fatigue (17% and 10%, respectively), diarrhea (4% and 7%, respectively), and hypertension (21% and 10%, respectively); grade 3 or 4 immune-related AEs included hepatitis (0% and 13%, respectively) and colitis (0% and 7%, respectively). The RP2D was cabozantinib 40 mg/d plus nivolumab 3 mg/kg for CaboNivo and cabozantinib 40 mg/d, nivolumab 3 mg/kg, and ipilimumab 1 mg/kg for CaboNivoIpi. ORR was 30.6% (95% CI, 20.0% to 47.5%) for all patients and 38.5% (95% CI, 13.9% to 68.4%) for patients with mUC. Median DoR was 21.0 months (95% CI, 5.4 to 24.1 months) for all patients and not reached for patients with mUC. Median PFS was 5.1 months (95% CI, 3.5 to 6.9 months) for all patients and 12.8 months (95% CI, 1.8 to 24.1 months) for patients with mUC. Median OS was 12.6 months (95% CI, 6.9 to 18.8 months) for all patients and 25.4 months (95% CI, 5.7 to 41.6 months) for patients with mUC. CONCLUSION CaboNivo and CaboNivoIpi demonstrated manageable toxicities with durable responses and encouraging survival in patients with mUC and other GU tumors. Multiple phase II and III trials are ongoing for these combinations.

"How much time do I have?" A patient's question about his/her life expectancy is among the most difficult of conversation topics. Oncologists, often with very little training in communication, routinely handle these requests for sensitive information. Oncologists are aware of the emotional weight surrounding a prognosis discussion: answering a prognosis question poorly can damage both a patient's sense of hope and the relationship with his/her physician. Conversely, when handled well, the discussion can affirm the relationship, build trust, and leave the patient feeling hopeful. Our review presents clinicians with a practical approach to handling prognosis discussions by dealing with 4 critical issues. First, we review what information should be conveyed about a patient's prognosis. Next, we provide tools to help the oncologist deal with a patient's emotional reaction. Then, we provide a framework for the discussion that helps preserve a patient's hope despite a poor prognosis. Finally, we address the impact on the physician and provide some suggestions for dealing with our own emotional reactions.

The goal of end-of-life (EoL) planning is to provide individuals with tools to control their financial and healthcare decisions when they are incapacitated. When an elderly patient is diagnosed with advanced cancer, the possible treatment

Background Stage III renal cell carcinoma (RCC) encompasses both lymph node‐positive (pT1‐3N1M0) and lymph node–negative (pT3N0M0) disease. However, prior institutional studies have indicated that among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease. The objective of the current study was to validate these findings using a large, nationally representative sample of patients with kidney cancer. Methods Patients with AJCC stage III or stage IV RCC were identified using the National Cancer Data Base (NCDB). Patients were categorized as having lymph node‐positive stage III (pT1‐3N1M0), lymph node–negative stage III (pT3N0M0), or stage IV metastatic (pT1‐3 N0M1) disease. Cox proportional hazards models compared outcomes while adjusting for comorbidities. Kaplan‐Meier estimates illustrated relative survival when comparing staging groups. Results A total of 8988 patients met the inclusion criteria, with 6587 patients classified as having lymph node–negative stage III disease, 2218 as having lymph node‐positive stage III disease, and 183 as having stage IV disease. Superior survival was noted among patients with lymph node–negative stage III disease, but similar survival was noted between patients with lymph node‐positive stage III and stage IV RCC, with 5‐year survival rates of 61.9% (95% confidence interval [95% CI], 60.3%‐63.4%), 22.7% (95% CI, 20.6%‐24.9%), and 15.6% (95% CI, 11.1%‐23.8%), respectively. Conclusions Current RCC staging systems group pT1‐3N1M0 and pT3N0M0 disease as stage III disease. However, the results of the current validation study suggest the need for further stratification and even placement of patients with pT1‐3N1M0 disease into the stage IV category. Staging that accurately reflects oncologic prognosis may help clinicians better counsel and select patients who might derive the most benefit from lymphadenectomy, adjuvant systemic therapy, more rigorous imaging surveillance, and clinical trial participation.

Purpose: This study investigated the efficacy and tolerability of cabozantinib plus nivolumab (CaboNivo) in patients with metastatic urothelial carcinoma (mUC) that progressed on checkpoint inhibition (CPI). Patients and Methods: A phase I expansion cohort of patients with mUC who received prior CPI was treated with cabozantinib 40 mg/day and nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary goal was objective response rate (ORR) per RECIST v.1.1. Secondary objectives included progression-free survival (PFS), duration of response (DoR), overall survival (OS), safety, and tolerability. Results: Twenty-nine out of 30 patients enrolled were evaluable for efficacy. Median follow-up was 22.2 months. Most patients (86.7%) received prior chemotherapy and all patients received prior CPI (median seven cycles). ORR was 16.0%, with one complete response and three partial responses (PR). Among 4 responders, 2 were primary refractory, 1 had a PR, and 1 had stable disease on prior CPI. Median DoR was 33.5 months [95% confidence interval (CI), 3.7–33.5], median PFS was 3.6 months (95% CI, 2.1–5.5), and median OS was 10.4 months (95% CI, 5.8–19.5). CaboNivo decreased immunosuppressive subsets such as regulatory T cells (Tregs) and increased potential antitumor immune subsets such as nonclassical monocytes and effector T cells. A lower percentage of monocytic myeloid-derived suppressor cells (M-MDSC) and polymorphonuclear MDSCs, lower CTLA-4 and TIM-3 expression on Tregs, and higher effector CD4+ T cells at baseline were associated with better PFS and/or OS. Conclusions: CaboNivo was clinically active, well tolerated, and favorably modulated peripheral blood immune subsets in patients with mUC refractory to CPI.