@article{3077687,
    title = "Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study)",
    author = "Schmidinger, M. and Bamias, A. and Procopio, G. and Hawkins, R. and Sanchez, A.R. and Vázquez, S. and Srihari, N. and Kalofonos, H. and Bono, P. and Pisal, C.B. and Hirschberg, Y. and Dezzani, L. and Ahmad, Q. and Jonasch, E. and Gimeno, R.A. and Herranz, U.A. and Ardavanis, A. and Ashraf, S.A. and Bamias, A. and Barone, C. and Bella, S.R. and Belz, H. and Companario, E.B. and Bolling, C. and Bono, P. and Bothe, K. and Carteni, G. and Espinosa, J.C. and Clausse, M. and Confente, C. and Coskun, H. and Herrero, G.C. and Demey, W. and D'hondt, R. and Santasusana, M.D. and Doshi, G. and Elkiran, E. and Facchini, G. and Fein, L. and Calvo, O.F. and Flaherty, A. and Fountzilas, G. and Fruehauf, J. and Díaz, E.G. and Garcia, R. and Domínguez, R.G. and Ghosn, M. and Glorieux, P. and Goebell, P.J. and Gutierrez, L.G.-A. and Gonzalez, M. and Green, N.B. and Arnau, M.G. and Harich, H.-D. and Hawkins, R. and Hegele, A. and Pérez, C.H. and Herrmann, E. and Horniniger, W.J. and Hutson, T.E. and Janetschek, G. and Kalantari, H. and Kalofonos, H. and Klausmann, M. and Kolin, M. and Krause, S. and Kroening, H. and Sorrosal, J.J.L. and Lázaro, M. and Lema, M. and Lema, M.L. and Lin, J. and Lueck, A. and Lybaert, W. and Magi, A. and Marina, V.A. and Rey, J.P.M. and Matus, G. and Melear, J. and Gonzalez, B.M. and Milella, M. and Montalar, J. and Ferrandis, J.M. and Nathan, P. and Nechushtan, H. and Nusch, A. and Ojamaa, K. and Oksuzoglu, B. and Ozkan, M. and Papazisis, K. and Passalacqua, R. and Pe'er, A. and Gracia, J.L.P. and Pichler, A. and Pokker, H. and Porta, C. and Rauchenwald, M. and Richardet, M.E. and Richey, S.L. and Garcia, J.M.R. and Sánchez, A.R. and Rudolph, R. and Sabbatini, R. and Salmon, J.-P. and Lobera, C.S. and Sarid, D.L. and Saylors, G.B. and Schmidinger, M. and Schrijvers, D. and Schulze, M. and Sevilay, A. and Shumaker, G.G. and Siemer, S. and de Prado y Otero, D.S. and Srihari, N. and Stoiber, F. and Rodriguez, C.S. and Varela, M.S. and Vasanthan, S. and Estevez, S.V. and Vehling-Kaiser, U. and Vogelzang, N. and Weiss, H. and Whenham, N. and Wyendaele, W. and Yildiz, R. and Yucel, I. and Zarba, J.J. and Zarkar, A. and Zhong, W. and Ziem, P. and the PRINCIPAL Study Group",
    journal = "The oncologist",
    year = "2019",
    volume = "24",
    number = "4",
    pages = "491-497",
    publisher = "John Wiley and Sons Inc",
    doi = "10.1634/theoncologist.2018-0787",
    keywords = "alanine aminotransferase;  pazopanib;  thyrotropin;  angiogenesis inhibitor;  pazopanib;  pyrimidine derivative;  sulfonamide, adult;  advanced cancer;  aged;  Article;  central nervous system metastasis;  coronary artery disease;  diarrhea;  disease exacerbation;  drug efficacy;  drug exposure;  drug safety;  drug withdrawal;  female;  human;  hypertension;  hypothyroidism;  International Metastatic Renal Cell Carcinoma Database Consortium score;  liver toxicity;  major clinical study;  male;  Memorial Sloan Kettering Cancer Center score;  nephrectomy;  observational study;  overall survival;  priority journal;  progression free survival;  prospective study;  quality of life;  renal cell carcinoma;  scoring system;  treatment response;  follow up;  kidney tumor;  middle aged;  pathology;  prognosis;  renal cell carcinoma;  survival rate;  treatment outcome;  very elderly;  young adult, Adult;  Aged;  Aged, 80 and over;  Angiogenesis Inhibitors;  Carcinoma, Renal Cell;  Female;  Follow-Up Studies;  Humans;  Kidney Neoplasms;  Male;  Middle Aged;  Prognosis;  Prospective Studies;  Pyrimidines;  Quality of Life;  Sulfonamides;  Survival Rate;  Treatment Outcome;  Young Adult",
    abstract = "Background: 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). Subjects, Materials, and Methods: 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. Results: 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. Conclusion: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. Implications for Practice: 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. © AlphaMed Press 2019"
}