TY - JOUR
TI - Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study)
AU - Schmidinger, M.
AU - Bamias, A.
AU - Procopio, G.
AU - Hawkins, R.
AU - Sanchez, A.R.
AU - Vázquez, S.
AU - Srihari, N.
AU - Kalofonos, H.
AU - Bono, P.
AU - Pisal, C.B.
AU - Hirschberg, Y.
AU - Dezzani, L.
AU - Ahmad, Q.
AU - Jonasch, E.
AU - Gimeno, R.A.
AU - Herranz, U.A.
AU - Ardavanis, A.
AU - Ashraf, S.A.
AU - Bamias, A.
AU - Barone, C.
AU - Bella, S.R.
AU - Belz, H.
AU - Companario, E.B.
AU - Bolling, C.
AU - Bono, P.
AU - Bothe, K.
AU - Carteni, G.
AU - Espinosa, J.C.
AU - Clausse, M.
AU - Confente, C.
AU - Coskun, H.
AU - Herrero, G.C.
AU - Demey, W.
AU - D'hondt, R.
AU - Santasusana, M.D.
AU - Doshi, G.
AU - Elkiran, E.
AU - Facchini, G.
AU - Fein, L.
AU - Calvo, O.F.
AU - Flaherty, A.
AU - Fountzilas, G.
AU - Fruehauf, J.
AU - Díaz, E.G.
AU - Garcia, R.
AU - Domínguez, R.G.
AU - Ghosn, M.
AU - Glorieux, P.
AU - Goebell, P.J.
AU - Gutierrez, L.G.-A.
AU - Gonzalez, M.
AU - Green, N.B.
AU - Arnau, M.G.
AU - Harich, H.-D.
AU - Hawkins, R.
AU - Hegele, A.
AU - Pérez, C.H.
AU - Herrmann, E.
AU - Horniniger, W.J.
AU - Hutson, T.E.
AU - Janetschek, G.
AU - Kalantari, H.
AU - Kalofonos, H.
AU - Klausmann, M.
AU - Kolin, M.
AU - Krause, S.
AU - Kroening, H.
AU - Sorrosal, J.J.L.
AU - Lázaro, M.
AU - Lema, M.
AU - Lema, M.L.
AU - Lin, J.
AU - Lueck, A.
AU - Lybaert, W.
AU - Magi, A.
AU - Marina, V.A.
AU - Rey, J.P.M.
AU - Matus, G.
AU - Melear, J.
AU - Gonzalez, B.M.
AU - Milella, M.
AU - Montalar, J.
AU - Ferrandis, J.M.
AU - Nathan, P.
AU - Nechushtan, H.
AU - Nusch, A.
AU - Ojamaa, K.
AU - Oksuzoglu, B.
AU - Ozkan, M.
AU - Papazisis, K.
AU - Passalacqua, R.
AU - Pe'er, A.
AU - Gracia, J.L.P.
AU - Pichler, A.
AU - Pokker, H.
AU - Porta, C.
AU - Rauchenwald, M.
AU - Richardet, M.E.
AU - Richey, S.L.
AU - Garcia, J.M.R.
AU - Sánchez, A.R.
AU - Rudolph, R.
AU - Sabbatini, R.
AU - Salmon, J.-P.
AU - Lobera, C.S.
AU - Sarid, D.L.
AU - Saylors, G.B.
AU - Schmidinger, M.
AU - Schrijvers, D.
AU - Schulze, M.
AU - Sevilay, A.
AU - Shumaker, G.G.
AU - Siemer, S.
AU - de Prado y Otero, D.S.
AU - Srihari, N.
AU - Stoiber, F.
AU - Rodriguez, C.S.
AU - Varela, M.S.
AU - Vasanthan, S.
AU - Estevez, S.V.
AU - Vehling-Kaiser, U.
AU - Vogelzang, N.
AU - Weiss, H.
AU - Whenham, N.
AU - Wyendaele, W.
AU - Yildiz, R.
AU - Yucel, I.
AU - Zarba, J.J.
AU - Zarkar, A.
AU - Zhong, W.
AU - Ziem, P.
AU - the PRINCIPAL Study Group
JO - The oncologist
PY - 2019
VL - 24
TODO - 4
SP - 491-497
PB - John Wiley and Sons Inc
SN - null
TODO - 10.1634/theoncologist.2018-0787
TODO - 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
TODO - 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
ER -