Type of publication:
Schmidinger M.; Procopio G.; Hawkins R.E.; Sanchez A.R.; Vazquez S.; *Srihari N.; Kalofonos H.; Bamias A.; Bono P.; Pisal C.B.; Hirschberg Y.; Dezzani L.; Ahmad Q.I.; Jonasch E.
Journal of Clinical Oncology; May 2018; vol. 36 (no. 15)
Background: PRINCIPAL (NCT01649778) was the largest prospective real-world effectiveness and safety study of pazopanib (PAZ) in patients (pts) with renal cell carcinoma (RCC). Method(s): Pts with advanced and/or metastatic clear cell RCC were enrolled within 30 days of initiating firstline PAZ. Follow-up data on progression, survival, and safety was collected approximately every 3 months until death, consent withdrawal, or loss to follow-up, for up to 30 months. Primary efficacy end points were median overall survival (mOS), median progression-free survival (mPFS), and overall response rate (ORR). Safety measures included frequency of adverse events (AEs), serious AEs, and AEs of special interest. Result(s): Among 657 pts who received >=1 dose of PAZ, 76.3% completed the study (33.0% completed 30 months of follow-up and 43.2% died). Median enrollment age was 66 years, with 57.2% aged >=65 years. 4.1%, 62.6%, and 33.3% of pts were grouped as favorable, intermediate, or poor risk by Heng criteria, respectively. Most pts (84%) initiated treatment at 800 mg, and the median treatment time with or without dose interruption was 6.9 and 7.6 months, respectively. mPFS and mOS are shown in the Table. Among the measurable disease population (n = 168), ORR was 30.3%, median duration of response was 11.0 months (95% confidence interval [CI] 8.6-14.6), and time to response, evaluated every 3 months, was 3.0 months (95% CI 2.9-3.1). Most pts had an AE (74.0%) that led to dose adjustment/interruption in 49.3% and treatment discontinuation in 14.6%. The most frequent ( > 10%) drug-related AEs were hypertension (20.9%), diarrhea (11.3%), and increased alanine aminotransferase (11.0%). Conclusion(s): Realworld effectiveness and safety outcomes in the PRINCIPAL study were consistent with clinical trials and support the first-line use of PAZ across all risk groups of pts with advanced or metastatic RCC.