Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study).

BACKGROUND: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). SUBJECTS, MATERIALS, AND METHODS: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups. RESULTS: Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2-12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. CONCLUSION: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. IMPLICATIONS FOR PRACTICE: PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors' knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months.

Long-term Clinical Outcomes of a Spanish Cohort of Metastatic Renal Cell Carcinoma Patients with a Complete Response to Sunitinib.

INTRODUCTION: The long-term clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) and a complete response (CR) to the tyrosine kinase inhibitor (TKI) sunitinib are poorly known. The characteristics of these patients could reveal previously undetected associations with clinical variables. PATIENTS AND METHODS: This observational, retrospective study (ATILA) used data from a registry of patients with mRCC who had received first-line sunitinib and had achieved CR from 2007 to 2018 in Spain. RESULTS: Sixty-two patients with CR were included; 48 patients (77.4%) received sunitinib in monotherapy and 14 (22.6%) combined with or followed by local treatment. Median age was 58.5 years (range, 32-81). Most patients (79.0%) had clear cell histology and had undergone previous nephrectomy (90.3%). The majority (70.2%) had an intermediate IMDC prognosis, 23% favorable and 7.0% poor. The median time on treatment with sunitinib was 28.2 months (IQR, 16.7-41.0) and the median time to CR was 10.9 months (IQR, 7.2-19.3). After a median follow-up of 8 years (range, 3-13 years), the median PFS was not reached. The overall median duration of complete response was 64.1 months (IQR, 32.2-99.4). The tolerance and safety profile of sunitinib was consistent with previous reports. CONCLUSION: Durable CR to sunitinib was observed in patients regardless the prognosis group, metastasis site or histology type, with 75% of patients remaining in CR after 10 years. CLINICALTRIALS: gov: NCT03916458.

Real-world Effectiveness and Safety of Pazopanib in Patients With Intermediate Prognostic Risk Advanced Renal Cell Carcinoma.

INTRODUCTION: The objective of this study was to determine the effectiveness and safety of pazopanib in patients with intermediate-risk advanced/metastatic renal cell carcinoma in the PRINCIPAL study (NCT01649778). PATIENTS AND METHODS: Patients had clear-cell advanced/metastatic renal cell carcinoma and met intermediate-risk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Assessments included progression-free survival, overall survival, objective response rate, and safety. We also evaluated effectiveness based on number of risk factors, age, and performance status (PS), as well as safety in older and younger patients. RESULTS: Three hundred sixty three and 343 intermediate-risk MSKCC and IMDC patients were included, respectively. The median progression-free survival was 13.8 months (95% confidence interval [CI], 10.7-18.1 months) and 7.4 months (95% CI, 6.2-10.3 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 13.1 months (95% CI, 10.7-18.1 months) and 8.1 months (95% CI, 6.4-10.7 months) for patients with 1 and 2 IMDC risk factors, respectively. The median overall survival was not reached and was 15.2 months (95% CI, 12.3-26.5 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 33.9 months (95% CI, 33.9 months to not estimable) and 19.4 months (95% CI, 14.3 months to not estimable) with 1 and 2 IMDC risk factors, respectively. A lower overall response rate was observed with Eastern Cooperative Oncology Group PS ≥ 2 (vs. PS < 2). All-grade treatment-related adverse events occurred in approximately 63% of patients, and the safety profile among older and younger patients was similar. CONCLUSIONS: Outcomes with pazopanib in intermediate-risk patients suggest that patients can be further stratified by number of risk factors (1 vs. 2) and Eastern Cooperative Oncology Group PS (< 2 vs. ≥ 2) to more accurately predict outcomes.