The treatment (tx) of metastatic renal cell carcinoma (mRCC) has markedly changed over the last decade with the introduction of targeted therapies including vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin (mTOR) inhibitors. Current tx recommendations include the VEGFR inhibitor pazopanib (PAZ) as first-line option and the mTOR inhibitor everolimus (EVE) after VEGF-targeted therapy. The approval of programmed cell death 1 (PD-1) checkpoint inhibitor nivolumab (NIVO) in 2016 provides an additional second-line option.
PAZOREAL is a prospective, non-interventional study to evaluate the effectiveness, tolerability, safety and quality of life on the routine tx of 450 adult patients (pts) with histologically confirmed mRCC treated with first-line PAZ, second-line EVE or NIVO, or third-line EVE after NIVO. The main objective is time on drug (TD) in the respective tx lines and overall, other objectives include overall survival, dosing parameters, safety and quality of life.
Between December 2015 and March 2017, 305 pts have been enrolled; 302 in the first-line PAZ cohort and 3 in third-line EVE after NIVO. The latter cohort was opened for documentation after approval of NIVO. 266 first-line pts had a documented first intake of PAZ and were eligible for analysis; 201 (75.6%) had a clear-cell histology. Median TD on PAZ was 6.5 months. For 98 pts (36.8%) discontinuation of PAZ tx was reported. The main reasons were progressive disease (N = 36), followed by toxicity (N = 18) and (serious) adverse event (N = 13). Details on subsequent tx with NIVO or EVE were documented for 24 and 4 pts, respectively, while 8 pts started other therapies in second line. During PAZ tx, the most frequently reported treatment-emergent adverse events (TEAE) of grade 1/2 were diarrhea (N = 57), nausea (N = 36), and fatigue (N = 24), of grade 3/4 were hypertension (N = 11), diarrhea and anemia (each N = 4). Fatal TEAEs were reported in 28 pts with progression being the most common term.
PAZ is an effective and safe first-line therapy for pts with mRCC in a real life setting. Second line therapy has rapidly shifted towards NIVO.
Clinical trial identification
BfArM AWB No. 6687
Legal entity responsible for the study
Novartis Pharma GmbH
Novartis Pharma GmbH
J. Bedke: Reports consultancies, honoraria or study participation from Bayer, Bristol-Myers Squib, Novartis, Pfizer and Roche. M. Welslau: Reports grants from Novartis, during the conduct of the study. M. Schostak: Reports grants and other from Novartis, during the conduct of the study; and honorarium from Novartis for scientific talks. C. Hering-Schubert: Reports grants from Roche, Novartis, Amgen, Bristol-Myers Squib Boehringer and Cellgene, outside the submitted work T. Wolf: Nothing to disclose. J. Schleicher: Reports grants and personal fees from Bristol-Myers Squib, Novartis; grants from Essai, Celegene; personal fees from Jansen, Pfizer, outside the submitted work. V. Grünwald: Advisory role at Pfizer, Novartis, Bristol-Myer Squibb, Ipsen, Eisai, Roche and has received honoraria from Pfizer, Novartis, Bristol-Myer Squibb, Ipsen, Eisai and Roche. Research support is given from Pfizer, Novartis, Bristol-Myers Squib and MSD Merck. R. Ehness: Employee of Novartis Pharma GmbH and holds stocks or stock options of Novartis and of GSK. D. Klein, T. Medinger: Employed at iOMEDICO AG. P.J. Goebell: Received honoraria for participation in expert rounds and honoraria/support as a speaker from Astellas, AstraZeneca, Bayer, Bristol-Myers Squib, Eisai, Ipsen, Janssen, Novartis, Pfizer, Sanofi. All other authors have declared no conflicts of interest.