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).
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.
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.
PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting.
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.
The oncologist. 2019 Mar 13 [Epub ahead of print]
Manuela Schmidinger, Aristotelis Bamias, Giuseppe Procopio, Robert Hawkins, Angel Rodriguez Sanchez, Sergio Vázquez, Narayanan Srihari, Haralabos Kalofonos, Petri Bono, Chaitali Babanrao Pisal, Yulia Hirschberg, Luca Dezzani, Qasim Ahmad, Eric Jonasch
Medical University of Vienna, Vienna, Austria ., National and Kapodistrian University of Athens Alexandra Hospital, Athens, Greece., Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., The Christie Hospital and University of Manchester, Manchester, United Kingdom., University Hospital of Leon, Leon, Spain., Hospital Universitario Lucus Augusti, Lugo, Spain., Shrewsbury & Telford Hospitals NHS Trust, Shrewsbury, United Kingdom., University of Patras, Patras, Greece., Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Novartis Healthcare Private Limited, Hyderabad, India., Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA., The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.