A Phase 2 Trial of Sunitinib in Patients with Advanced Non–clear Cell Renal Cell Carcinoma

Abstract

Background Sunitinib is a standard of care treatment in advanced clear-cell renal cell carcinoma (ccRCC). Retrospective and expanded access data suggest sunitinib has activity in advanced non-clear cell RCC (nccRCC). Objective To prospectively determine the clinical efficacy and safety of sunitinib in patients with advanced nccRCC. Design, Setting, and Participants This is a single-arm phase 2 trial with a two-stage design. Eligibility criteria included pathologically confirmed nccRCC or ccRCC with ≥ 20 percent sarcomatoid histology, performance status 0–2, measurable disease, maximum 2 prior systemic therapies, and no prior treatment with tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptors. Intervention Patients received sunitinib 50 mg daily on a 4-week on, 2-week off schedule. Outcome Measurements and Statistical Analysis Primary endpoints were objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints were safety and overall survival (OS). Results and Limitations Fifty-seven patients were eligible [papillary (27), chromophobe (5), unclassified (8), collecting duct or medullary carcinoma (6), sarcomatoid (7), others (4)]. Median PFS for 55 evaluable patients was 2.7 months [95% CI: 1.4, 5.4]. Two patients with chromophobe and one patient with unclassified histology had a confirmed partial response (5% ORR). Median PFS for patients with papillary histology was 1.6 months (95% CI: 1.4, 5.4). Median PFS for patients with chromophobe histology was 12.7 months (95% CI: 8.5, NA). Median OS for all patients was 16.8 months (95% CI: 10.7, 26.3). Treatment emergent adverse events were consistent with sunitinib’s mechanism of action. The non-randomized design and small number of patients are limitations of this study. Conclusions The differential response of chromophobe histology to sunitinib suggests a therapeutically relevant biological heterogeneity exists within nccRCC. The low ORR and short PFS with sunitinib in the other nccRCC subtypes underscore the need to enroll patients with these diverse tumors on clinical trials.

Hypertension and Circulating Cytokines and Angiogenic Factors in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma Treated With Sunitinib: Results From a Phase II Trial

“…The clinical study has been previously described [3]. The primary endpoints were the objective response rate and progression-free survival (PFS).The secondary endpoints were safety and overall survival (OS).…”

“…The disease characteristics have been previously summarized [3]. Of the 57 patients, 27 (47%) had papillary RCC (2 with type I, 11 with type II, and 14 not specified), 8 (14%) had an unclassified variant, 7 (12%) had sarcomatoid, 6 (11%) had collecting duct/ renal medullary, 5 (9%) had chromophobe, and 4 (7%) had other forms of nccRCC.…”

Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

“…[160][161][162][163][164][165][166][167] A phase II trial of 31 patients with non-clear cell RCC treated with sunitinib reported an ORR of 36% (95% CI, 19%-52%) and median PFS of 6.4 months (95% CI, 4.2-8.6 months). 165 In another study of 53 patients with non-clear cell RCC (papillary or chromophobe), the ORR to sunitinib or sorafenib was 23%; median PFS was 10.6 months.…”

Current treatment approach to non-clear cell renal carcinoma

“…A. Bilen и соавт. представили результаты иссле-дования II фазы, в котором оценивали зависимость эффективности сунитиниба от развития гипертензии, а также циркулирующих цитокинов и ангиогенных факторов у больных нПКР [41,42]. Сунитиниб полу-чали 57 пациентов с папиллярным, хромофобным, медуллярным, неклассифицируемым ПКР и раком из собирательных трубочек.…”