ASCO GU 2020: Prospective Observational Study on Pazopanib in Patients Treated for Advanced/Metastatic Renal Cell Carcinoma: APOLON Study

Pazopanib is a multi-tyrosine kinase inhibitor that limits tumor growth by targeting angiogenesis via inhibition of vascular endothelial growth factor (VEGF) receptor, platelet-derived growth factor receptor, c-KIT and fibroblast growth factor receptor. Based on clinical trial data, pazopanib has been approved for the management of advanced or metastatic renal cell carcinoma (RCC). However, as clinical trials generally have strict inclusion criteria, the real-world efficacy and safety of pazopanib in the general public has yet to be completely evaluated.

Dr. Philippe Barthelemy presented an observational prospective study across 55 centers to assess the efficacy and safety of pazopanib in patients with metastatic RCC naïve to anti-VEGF therapy. All patients included in the analysis initiated pazopanib therapy within standard medical practice, and data were collected at baseline and at 1, 2-3, 6, 9, 12, 18, 24, 30, 36 months. The primary endpoint was assessment of 8-month progression-free survival (PFS) rate. The secondary endpoints were overall survival, objective response rate (ORR), tolerability, and subsequent post-pazopanib therapy.

Of 218 patients that met inclusion criteria for analysis, 71.1% were male and the median age was 69.6 years. Patient comorbidities included hypertension (75.1%), diabetes (26.0%), arterial disorders (20.1%), and other pathologies (47.3%). Stratified by ECOG performance status (PS), 42.9% were ECOG PS 0, 40.0% were ECOG PS 1, and 15.7% were ECOG PS 2. With regards to tumor characteristics, 97.7% had clear cell RCC. Stratified by International Metastatic RCC Database Consortium risk criteria, 26.4% were favorable risk, 52.9% were intermediate risk, and 20.7% were poor risk. The major sites of RCC metastases included the lungs (62.8%), bones (28.9%), mediastinal lymph nodes (17.9%), abdominal lymph nodes (17.0%), and glands (pancreas, thyroid, adrenals) (17.4%). Of the patients included in the study, 56.0% had previously undergone a partial or total nephrectomy, and 28% had previously undergone local treatments for metastases.

With regards to the primary outcome, the 8-month PFS rate was 62.9% and the median PFS was 11.3 months. With regards to secondary outcomes, the 1-year overall survival rate was 71.2% and ORR was 47.2%. Serious adverse events related to treatment were reported in 17.3% of patients, and the most frequent complications were diarrhea, general physical health deterioration, hypertension, and hepatocellular injury. At a median follow-up of 8.8 months, 121 patients discontinued pazopanib and 74 patients received post-pazopanib treatment. Initial post-pazopanib treatment included nivolumab (67.6%), cabozantinib (16.2%), sunitinib (10.8%), and other (5.6%).

Dr. Barthelemy concluded that the APOLON study represents a real-world evaluation of the efficacy and safety of pazopanib in patients with advanced or metastatic RCC. This study is notable because it included both elderly and frail patients. Utilization of pazopanib in patients with advanced or metastatic RCC in routine clinical practice resulted in clinically significant improvements in PFS, OS, and ORR. Also, the adverse effect profile of pazopanib noted in this study is consistent with prior studies.

Presented by: Philippe Barthelemy, MD, PhD, Strasbourg University Hospital, Strasbourg, France

Written By: Ziho Lee, MD, Fellow in Advanced Robotic Oncology and Reconstruction, Temple University, Philadelphia, PA,Twitter: @ZLeeGU at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
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