Type of publication:
Jonasch E.; 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.; Schmidinger M.
Journal of Clinical Oncology; May 2018; vol. 36 (no. 15)
Background: Although pazopanib (PAZ) has been evaluated in clinical trials of patients (pts) with renal cell carcinoma (RCC), limited real-world data on the effectiveness and safety of PAZ exist. The PRINCIPAL study (NCT01649778) assessed the effectiveness and safety of first-line PAZ in a real-world setting. Method(s): In this nonrandomized, prospective study, pts with advanced and/or metastatic clear cell RCC were enrolled in PRINCIPAL within 30 days of initiating first-line PAZ. Data on progression, survival, and safety were collected approximately every 3 months (mos) until death, consent withdrawal, or loss to follow-up, for up to 30 mos. Pts in PRINCIPAL were separated into two groups based on key eligibility criteria from the Phase III COMPARZ trial (Motzer et al. NEJM. 2013;369:722). Key clinical trial eligible (CTE) criteria included no prior systemic therapy, presence of measurable disease per RECIST 1.1, Karnofsky performance status >=70, adequate organ system function, no history or clinical evidence of central nervous system metastases, and no coronary or cerebral artery disease at baseline. CTE pts were compared to non-CTE (NCTE) pts. Clinical effectiveness (ie, median overall survival [mOS], median progression-free survival [mPFS], and overall response rate [ORR]), adverse event (AE) measures, and relative dose intensity (RDI) were assessed in both pt populations. Result(s): Of the 657 enrolled pts who received >=1 dose of PAZ, 97 (14.8%) were CTE and 560 (85.2%) were NCTE. RDI >=85% was achieved in 70.1% and 56.6% in the CTE and NCTE populations, respectively. Effectiveness was similar in the CTE and the NCTE populations (mPFS, 9.6 vs 10.7 mos; ORR, 33.0% vs 29.8%; mOS, 26.3 vs 32.9 mos). Serious AEs were reported by 23.7% of CTE and 28.2% of NCTE pts. AEs led to dose adjustment/interruption in 83.5% and 95.2%, respectively, and AEs led to treatment discontinuation in 8.2% of the CTE and 15.5% NCTE pts. Conclusion(s): The results of the PRINCIPAL study suggest that first-line PAZ for pts with advanced or metastatic RCC remains effective and safe in a real-world setting, showing similar outcomes to those reported in large randomized clinical trials.