Abstract 718P
Background
Immune checkpoint inhibitors (ICIs) are increasingly used in the initial treatment of mRCC. The aim of this study was to evaluate the safety and efficacy of the vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) pazopanib (PAZ) in patients with advanced or mRCC following previous ICI treatment.
Methods
This was an international, single arm, phase II trial (NCT03200717). Patients with histologically confirmed locally recurrent or metastatic clear cell RCC and prior ICI therapy received PAZ 800 mg once daily until progression, unacceptable toxicity, death, or study withdrawal. The primary endpoint was progression-free survival (PFS) based on local investigator assessment; secondary endpoints were overall response rates (ORR) based on local investigator assessment, overall survival (OS), and safety. This primary analysis was conducted when all patients had received ≥6 treatment cycles (median follow-up, 10.2 months).
Results
A total of 62 patients previously treated with ICI were enrolled and received PAZ as 2nd line (2L) (n=47; 25% had prior anti-VEGF therapy) or 3rd line (3L) (n=15, 100% had prior anti-VEGF therapy) treatment. IMDC prognosis at baseline was favorable, intermediate, or poor in 32.3%, 56.5%, and 11.3% of patients, respectively. In patients receiving 2L PAZ, median PFS was 7.4 months (95% CI: 3.7, 13.8) and survival probability at 12 months was 65.8% (95% CI: 48.5%, 78.4%). In the 3L setting, median PFS was 4.6 months (95% CI: 3.3, 9.2) and survival probability at 12 months was 75.8% (95% CI: 40.4%, 91.9%). ORR was 19% in the 2L and 0% in the 3L setting. The most common treatment-related adverse events (AEs) were diarrhea (40%), liver abnormalities (34%), fatigue (31%), decreased appetite (26%), and nausea (24%). Nineteen patients (31%) reported AEs leading to treatment withdrawal, of which 10 (16%) were due to liver abnormalities; 44 patients (71%) had AEs requiring dose adjustment or interruption. Grade 3/4 transaminase elevations per lab data occurred in 15/62 patients (24.2%), but no deaths were related to transaminitis.
Conclusions
PAZ has activity after progression on ICIs in mRCC. AE profiles are in line with the expectations for this TKI.
Clinical trial identification
NCT03200717.
Editorial acknowledgement
Tim Ibbotson, ApotheCom.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
T.B. Powles: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self), Research grant/Funding (institution): Exelixis; Honoraria (self): Incyte; Honoraria (self), Research grant/Funding (institution): Merck/MSD; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Research grant/Funding (institution): Seattle Genetics; Honoraria (self), Research grant/Funding (institution): Merck Serono; Honoraria (self), Research grant/Funding (institution): Astellas; Honoraria (self), Research grant/Funding (institution): Johnson & Johnson; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution), Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: MSD. S. Oudard: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: Sanofi. V. Grünwald: Advisory/Consultancy, Research grant/Funding (self), Non-remunerated activity/ies: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self), Non-remunerated activity/ies: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (self), Non-remunerated activity/ies: Ipsen; Research grant/Funding (self), Non-remunerated activity/ies: Pfizer; Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (self): Merck Sharp and Dohme; Non-remunerated activity/ies: Bayer; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: EUSAPharm; Advisory/Consultancy: Eisai; Advisory/Consultancy: Roche; Advisory/Consultancy: Janssen-Cilag; Advisory/Consultancy: Asklepios Clinic; Advisory/Consultancy: Diakonie Clinic; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Dortmund Hospital; Advisory/Consultancy: Clinic of Oldenburg; Advisory/Consultancy: Onkowissen. E. Calvo: Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (self): Amcure; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Advisory/Consultancy: Janssen-Cilag, Seattle Genetics, Pierre Fabre, Cerulean Pharma, EUSA, Celgene, Novartis, Nanobiotix, PsiOxus Therapeutics, AbbVie, AstraZeneca, Guidepoint Global, Roche/Genentech, GLG, Pfizer, Servier, and Amcure; Full/Part-time employment, is an owner or has employment : START, HM Hospitals Group, Oncoart Associated, and International Cancer Consultants; Honoraria (self): HM Hospitals Group; Research grant/Funding (self): PUMA, Sanofi, Lilly, Pfizer, Merck, Nektar, Amcure, Amgen, AstraZeneca, Principia Bayer, CytomX, H3, Incyte, Kura, LOXO, Macrogenics, Menarini, Merck Serono, Merus, Millenium, Rigontec, Tahio, Tesaro, START, Novartis, AstraZeneca and Beigene; Full/Part-time employment, is President and Founder : NPO Foundation Intheos. M.D. Michaelson: Officer/Board of Directors: Exelixis; Officer/Board of Directors: Pfizer; Officer/Board of Directors: Eisai; Research grant/Funding (self), payment for development of educational presentations: NCCN. M. Burotto: Advisory/Consultancy, Speaker Bureau/Expert testimony, Officer/Board of Directors: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Officer/Board of Directors: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Officer/Board of Directors: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Officer/Board of Directors: Novartis; Speaker Bureau/Expert testimony, Officer/Board of Directors: Roche. B. Melichar: Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp and Dohme; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Astellas; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Serono; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Servier; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy: Amgen; Advisory/Consultancy: Janssen; Advisory/Consultancy: Eisai; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Ipsen. R. Tyagi: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis Pharmaceutical Corporation. F. Hilmi: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis Pharmaceutical Corporation. A. Gaur: Full/Part-time employment: Novartis Pharmaceutical Corporation. Y. Hirschberg: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis Pharmaceutical Corporation. D. Heng: Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: BMS; Advisory/Consultancy: Merck; Advisory/Consultancy: Ipsen.