Efficacy and Safety of Nivolumab Plus Ipilimumab versus Sunitinib in First-line Treatment of Patients with Advanced Sarcomatoid Renal Cell Carcinoma.

PURPOSE: Patients with advanced renal cell carcinoma with sarcomatoid features (sRCC) have poor prognoses and suboptimal outcomes with targeted therapy. This post hoc analysis of the phase III CheckMate 214 trial analyzed the efficacy of nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib in patients with sRCC. PATIENTS AND METHODS: Patients with sRCC were identified via independent central pathology review of archival tumor tissue or histologic classification per local pathology report. Patients were randomized 1:1 to receive nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) every 3 weeks (four doses) then nivolumab 3 mg/kg every 2 weeks, or sunitinib 50 mg orally every day (4 weeks; 6-week cycles). Outcomes in patients with sRCC were not prespecified. Endpoints in patients with sRCC and International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor-risk disease included overall survival (OS), progression-free survival (PFS) per independent radiology review, and objective response rate (ORR) per RECIST v1.1. Safety outcomes used descriptive statistics. RESULTS: Of 1,096 randomized patients in CheckMate 214, 139 patients with sRCC and intermediate/poor-risk disease and six with favorable-risk disease were identified. With 42 months' minimum follow-up in patients with sRCC and intermediate/poor-risk disease, median OS [95% confidence interval (CI)] favored NIVO+IPI [not reached (NR) (25.2-not estimable [NE]); n = 74] versus sunitinib [14.2 months (9.3-22.9); n = 65; HR, 0.45 (95% CI, 0.3-0.7; P = 0.0004)]; PFS benefits with NIVO+IPI were similarly observed [median 26.5 vs. 5.1 months; HR, 0.54 (95% CI, 0.33-0.86; P = 0.0093)]. Confirmed ORR was 60.8% with NIVO+IPI versus 23.1% with sunitinib, with complete response rates of 18.9% versus 3.1%, respectively. No new safety signals emerged. CONCLUSIONS: NIVO+IPI showed unprecedented long-term survival, response, and complete response benefits versus sunitinib in previously untreated patients with sRCC and intermediate/poor-risk disease, supporting the use of first-line NIVO+IPI for this population.See related commentary by Hwang et al., p. 5.

Patient-Reported Outcomes from the Phase III Randomized IMmotion151 Trial: Atezolizumab + Bevacizumab versus Sunitinib in Treatment-Naïve Metastatic Renal Cell Carcinoma.

PURPOSE: Patient-reported outcomes (PRO) were evaluated in the phase III IMmotion151 trial (NCT02420821) to inform overall treatment/disease burden of atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Patients were randomized 1:1 to receive atezolizumab 1,200 mg intravenous (i.v.) infusions every 3 weeks (q3w) plus bevacizumab 15 mg/kg i.v. q3w or sunitinib 50 mg per day orally 4 weeks on/2 weeks off. Patients completed the MD Anderson Symptom Inventory (MDASI), National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19), and Brief Fatigue Inventory (BFI) at baseline, q3w during treatment, at end of treatment, and during survival follow-up. Longitudinal and time to deterioration (TTD) analyses for core and RCC symptoms and their interference with daily life, treatment side-effect bother, and health-related quality of life (HRQOL) were evaluated. RESULTS: The intent-to-treat population included 454 and 461 patients in the atezolizumab plus bevacizumab and sunitinib arms, respectively. Completion rates for each instrument were 83% to 86% at baseline and ≥ 70% through week 54. Milder symptoms, less symptom interference and treatment side-effect bother, and better HRQOL at most visits were reported with atezolizumab plus bevacizumab versus sunitinib. The TTD HR (95% CI) favored atezolizumab plus bevacizumab for core (HR, 0.50; 0.40-0.62) and RCC symptoms (HR, 0.45; 0.37-0.55), symptom interference (HR, 0.56; 0.46-0.68), and HRQOL (HR, 0.68; 0.58-0.81). CONCLUSIONS: PROs in IMmotion151 suggest lower overall treatment burden with atezolizumab plus bevacizumab compared with sunitinib in patients with treatment-naïve mRCC and provide further evidence for clinical benefit of this regimen.

Health economic changes as a result of implementation of targeted therapy for metastatic renal cell carcinoma: national results from DARENCA study 2.

BACKGROUND: Limited data exist on the economic consequences of implementing targeted therapy (TT) for metastatic renal cell carcinoma (RCC) in a real-world setting. OBJECTIVE: To analyze health care and productivity costs for TT implementation in a national cohort of patients. DESIGN, SETTING, AND PARTICIPANTS: Costs were measured per patient per year during a 2-yr follow-up during 2002-2005 (immunotherapy only) and 2006-2009 (TT implementation). All Danish patients with a diagnosis code for RCC and a procedure code for TT or immunotherapy were linked to the Danish National Patient Registry (contains information on all contacts with primary and secondary health sector). Health care and productivity costs were retrieved from the Danish case-mix system and Coherent Social Statistics, respectively. Drug costs were calculated separately from procedure codes and retail prices. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Generalized linear models were used to analyze costs adjusted for age, gender, and civil status. RESULTS AND LIMITATIONS: A total of 439 patients were included for 2006-2009 and 192 for 2002-2005. Comparison of the health care cost per patient per year between 2006-2009 and 2002-2005 revealed lower inpatient costs (€11 899 vs €19 944, adjusted relative risk [RR] 0.64), higher outpatient costs (€14 308 vs €6209, RR 2.39), lower radiotherapy costs (€194 vs €633, RR 0.31), higher radiology costs (€676 vs €191, RR 3.73), and higher separately calculated drug costs (€12 040 vs €3103, RR 3.82, all p<0.001) for the former. Total health care costs per patient per year did not significantly differ (€27 676 vs €27 856, RR 1.05, p=0.5) between the two periods. Income from employment did not significantly differ between 2006-2009 and 2002-2005 (RR 1.11, p=0.11) and costs associated with loss of productivity were €7852 and €8265, respectively. CONCLUSIONS: A different pattern of health care costs were observed but total health care costs per patient per year did not significantly differ after implementation of TT for patients with mRCC. PATIENT SUMMARY: In this nationwide study, we found changes in the pattern of health care costs for patients with metastatic kidney cancer after implementation of targeted therapy compared to an immunotherapy control period; however, total health care costs and income from employment were without significant changes.

Efficacy of targeted therapy for metastatic renal cell carcinoma in the elderly patient population.

INTRODUCTION/BACKGROUND: Targeted therapy has become the mainstay of treatment for mRCC. The efficacy of this therapy in the older population is poorly understood. PATIENTS AND METHODS: Data from patients with mRCC treated with first-line anti-VEGF therapy were collected through the International mRCC Database Consortium from 12 centers. Patient characteristics, data on second-line therapy, and outcomes including treatment duration and overall survival, were evaluated using summary statistics and multivariate analysis. RESULTS: All patients (n = 1381) were treated with front-line targeted therapy; 144 (10%) were 75 years old or older. Six patients (4%) were favorable risk, 99 patients (69%) intermediate risk, and 39 patients (27%) poor risk according to Heng Journal of Clinical Oncology 2009 prognostic factors. The initial treatment for those ≥ 75 years of age was sunitinib (n = 98), sorafenib (n = 35), bevacizumab (n = 7), and AZD217 (n = 4). Twenty-three percent of older patients and 39% of the younger patients went on to receive second-line therapy (P < .0001). The overall response rate, median treatment duration, and overall survival for the older versus younger group were 18% versus 25% (P = .0975), 5.5 months versus 7.5 months (P = .1388), and 16.8 months versus 19.7 months (P = .3321), respectively. When adjusted for poor prognostic factors, age 75 years and older was not found to be associated with poorer overall survival (hazard ratio [HR], 1.002; 95% confidence interval [CI], 0.781-1.285) or shorter treatment duration (HR, 1.018; 95% CI, 0.827-1.252). The retrospective study design was the primary limitation. CONCLUSION: The use of advanced age as a selection criterion for targeted therapy requires further study, with data suggesting no clinically meaningful differences in overall response rate, treatment duration, and overall survival between older and younger age groups.

Combination of zoledronic Acid and targeted therapy is active but may induce osteonecrosis of the jaw in patients with metastatic renal cell carcinoma.

PURPOSE: To investigate the efficacy and safety of zoledronic acid (ZA) combined with targeted therapy (TT). MATERIALS AND METHODS: A retrospective study was performed in patients with metastatic renal cell carcinoma treated with ZA and TT. RESULTS: Twenty-one patients received ZA and TT to prevent skeletal-related events and no pretherapy oral and maxillofacial (OM) examination (cohort A). Six patients (29%) developed osteonecrosis of the jaw (ONJ), which was observed only in patients receiving sunitinib and ZA. Sixteen patients received TT and ZA for hypercalcemia and no pretherapy OM examination (cohort B). In these patients, no ONJ was observed. Nine patients received ZA and TT and pretherapy OM examination (cohort C). One patient (11%) developed ONJ during sunitinib and ZA treatment. Mean skeletal morbidity rates were 0.8 for cohort A and 1.2 for cohort C. In the combined cohort (A plus C; n = 30), 47% developed skeletal-related events, 7% pathologic fracture, 7% medullary compression, and 37% progression of bone metastases. Patients who developed ONJ had a significantly improved median survival of 31.6 months compared with 14.5 months in patients without ONJ (P = .039). CONCLUSION: The combination of ZA and TT resulted in high, clinically meaningful activity. ONJ may be exacerbated by concomitant ZA and sunitinib. Regular OM examinations before and during treatment are recommended.