PMID- 30867244 OWN - NLM STAT- MEDLINE DCOM- 20200520 LR - 20211204 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 24 IP - 4 DP - 2019 Apr TI - Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study). PG - 491-497 LID - 10.1634/theoncologist.2018-0787 [doi] AB - 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. CI - (c) AlphaMed Press 2019. FAU - Schmidinger, Manuela AU - Schmidinger M AD - Medical University of Vienna, Vienna, Austria manuela.schmidinger@meduniwien.ac.at. FAU - Bamias, Aristotelis AU - Bamias A AD - National and Kapodistrian University of Athens Alexandra Hospital, Athens, Greece. FAU - Procopio, Giuseppe AU - Procopio G AD - Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. FAU - Hawkins, Robert AU - Hawkins R AD - The Christie Hospital and University of Manchester, Manchester, United Kingdom. FAU - Sanchez, Angel Rodriguez AU - Sanchez AR AD - University Hospital of Leon, Leon, Spain. FAU - Vazquez, Sergio AU - Vazquez S AD - Hospital Universitario Lucus Augusti, Lugo, Spain. FAU - Srihari, Narayanan AU - Srihari N AD - Shrewsbury & Telford Hospitals NHS Trust, Shrewsbury, United Kingdom. FAU - Kalofonos, Haralabos AU - Kalofonos H AD - University of Patras, Patras, Greece. FAU - Bono, Petri AU - Bono P AD - Helsinki University Hospital and University of Helsinki, Helsinki, Finland. FAU - Pisal, Chaitali Babanrao AU - Pisal CB AD - Novartis Healthcare Private Limited, Hyderabad, India. FAU - Hirschberg, Yulia AU - Hirschberg Y AD - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. FAU - Dezzani, Luca AU - Dezzani L AD - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. FAU - Ahmad, Qasim AU - Ahmad Q AD - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. FAU - Jonasch, Eric AU - Jonasch E AD - The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. CN - PRINCIPAL Study Group LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20190313 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Indazoles) RN - 0 (Pyrimidines) RN - 0 (Sulfonamides) RN - 7RN5DR86CK (pazopanib) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Angiogenesis Inhibitors/*therapeutic use MH - Carcinoma, Renal Cell/*drug therapy/secondary MH - Female MH - Follow-Up Studies MH - Humans MH - Indazoles MH - Kidney Neoplasms/*drug therapy/pathology MH - Male MH - Middle Aged MH - Prognosis MH - Prospective Studies MH - Pyrimidines/*therapeutic use MH - Quality of Life MH - Sulfonamides/*therapeutic use MH - Survival Rate MH - Treatment Outcome MH - Young Adult PMC - PMC6459236 OTO - NOTNLM OT - Observational OT - Pazopanib OT - Real-world OT - Renal cell carcinoma OT - Tyrosine kinase inhibitor COIS- Disclosures of potential conflicts of interest may be found at the end of this article. FIR - Gimeno, Ramon Aldabo IR - Gimeno RA FIR - Herranz, Urbano Anido IR - Herranz UA FIR - Ardavanis, Alexandros IR - Ardavanis A FIR - Ashraf, Safeer A IR - Ashraf SA FIR - Bamias, Aristotelis IR - Bamias A FIR - Barone, Carlo IR - Barone C FIR - Bella, Santiago R IR - Bella SR FIR - Belz, Hanjo IR - Belz H FIR - Companario, Esperanza Blanco IR - Companario EB FIR - Bolling, Claus IR - Bolling C FIR - Bono, Petri IR - Bono P FIR - Bothe, Katrin IR - Bothe K FIR - Carteni, Giacomo IR - Carteni G FIR - Espinosa, Javier Cassinello IR - Espinosa JC FIR - Clausse, Marylene IR - Clausse M FIR - Confente, Caterina IR - Confente C FIR - Coskun, Hasan IR - Coskun H FIR - Herrero, Guillermo Crespo IR - Herrero GC FIR - Demey, Wim IR - Demey W FIR - D'hondt, Randal IR - D'hondt R FIR - Santasusana, Montserrat Domenech IR - Santasusana MD FIR - Doshi, Gury IR - Doshi G FIR - Elkiran, Emin IR - Elkiran E FIR - Facchini, Gaetano IR - Facchini G FIR - Fein, Luis IR - Fein L FIR - Calvo, Ovidio Fernandez IR - Calvo OF FIR - Flaherty, Amber IR - Flaherty A FIR - Fountzilas, George IR - Fountzilas G FIR - Fruehauf, John IR - Fruehauf J FIR - Diaz, Enrique Gallardo IR - Diaz EG FIR - Garcia, Rosa IR - Garcia R FIR - Dominguez, Rocio Garcia IR - Dominguez RG FIR - Ghosn, Marwan IR - Ghosn M FIR - Glorieux, Philippe IR - Glorieux P FIR - Goebell, Peter J IR - Goebell PJ FIR - Gutierrez, Lorenzo Gomez-Aldaravi IR - Gutierrez LG FIR - Gonzalez, Manuel IR - Gonzalez M FIR - Green, Nathan B IR - Green NB FIR - Arnau, Marta Guix IR - Arnau MG FIR - Harich, Hanns-Detlev IR - Harich HD FIR - Hawkins, Robert IR - Hawkins R FIR - Hegele, Axel IR - Hegele A FIR - Perez, Carolina Hernandez IR - Perez CH FIR - Herrmann, Edwin IR - Herrmann E FIR - Horniniger, Wolfgang J IR - Horniniger WJ FIR - Hutson, Thomas E IR - Hutson TE FIR - Janetschek, Gunter IR - Janetschek G FIR - Kalantari, Hassan IR - Kalantari H FIR - Kalofonos, Haralabos IR - Kalofonos H FIR - Klausmann, Martine IR - Klausmann M FIR - Kolin, Maya IR - Kolin M FIR - Krause, Steffen IR - Krause S FIR - Kroening, Hendrick IR - Kroening H FIR - Sorrosal, Julio Jose Lambea IR - Sorrosal JJL FIR - Lazaro, Martin IR - Lazaro M FIR - Lema, Mauricio IR - Lema M FIR - Lema, Mauricio L IR - Lema ML FIR - Lin, Johnson IR - Lin J FIR - Lueck, Andreas IR - Lueck A FIR - Lybaert, Willem IR - Lybaert W FIR - Magi, Andrus IR - Magi A FIR - Marina, Virginia A IR - Marina VA FIR - Rey, Jose Pablo Maroto IR - Rey JPM FIR - Matus, Geoffrey IR - Matus G FIR - Melear, Jason IR - Melear J FIR - Gonzalez, Begona Mellado IR - Gonzalez BM FIR - Milella, Michele IR - Milella M FIR - Montalar, Joaquin IR - Montalar J FIR - Ferrandis, Javier Munarriz IR - Ferrandis JM FIR - Nathan, Paul IR - Nathan P FIR - Nechushtan, Hovav IR - Nechushtan H FIR - Nusch, Arnd IR - Nusch A FIR - Ojamaa, Kritiina IR - Ojamaa K FIR - Oksuzoglu, Berna IR - Oksuzoglu B FIR - Ozkan, Metin IR - Ozkan M FIR - Papazisis, Konstantinos IR - Papazisis K FIR - Passalacqua, Rodolfo IR - Passalacqua R FIR - Pe'er, Avivit IR - Pe'er A FIR - Gracia, Jose Luis Perez IR - Gracia JLP FIR - Pichler, Angelika IR - Pichler A FIR - Pokker, Hellis IR - Pokker H FIR - Porta, Camillo IR - Porta C FIR - Procopio, Giuseppe IR - Procopio G FIR - Rauchenwald, Michael IR - Rauchenwald M FIR - Richardet, Martin E IR - Richardet ME FIR - Richey, Stephen L IR - Richey SL FIR - Garcia, Jose Manuel Rodriguez IR - Garcia JMR FIR - Sanchez, Angel Rodriguez IR - Sanchez AR FIR - Rudolph, Robert IR - Rudolph R FIR - Sabbatini, Roberto IR - Sabbatini R FIR - Salmon, Jean-Paul IR - Salmon JP FIR - Lobera, Carmen Santander IR - Lobera CS FIR - Sarid, David L IR - Sarid DL FIR - Saylors, Gene B IR - Saylors GB FIR - Schmidinger, Manuela IR - Schmidinger M FIR - Schrijvers, Dirk IR - Schrijvers D FIR - Schulze, Matthias IR - Schulze M FIR - Sevilay, Altintas IR - Sevilay A FIR - Shumaker, Grace G IR - Shumaker GG FIR - Siemer, Stefan IR - Siemer S FIR - de Prado Y Otero, Diego Soto IR - de Prado Y Otero DS FIR - Srihari, Narayanan IR - Srihari N FIR - Stoiber, Franz IR - Stoiber F FIR - Rodriguez, Cristina Suarez IR - Rodriguez CS FIR - Varela, Mirta S IR - Varela MS FIR - Vasanthan, Subramaniam IR - Vasanthan S FIR - Estevez, Sergio Vazquez IR - Estevez SV FIR - Vehling-Kaiser, Ursula IR - Vehling-Kaiser U FIR - Vogelzang, Nicholas IR - Vogelzang N FIR - Weiss, Harald IR - Weiss H FIR - Whenham, Nicolas IR - Whenham N FIR - Wyendaele, Wim IR - Wyendaele W FIR - Yildiz, Ramazan IR - Yildiz R FIR - Yucel, Idris IR - Yucel I FIR - Zarba, Juan J IR - Zarba JJ FIR - Zarkar, Anjali IR - Zarkar A FIR - Zhong, Wangjian IR - Zhong W FIR - Ziem, Patrick IR - Ziem P EDAT- 2019/03/15 06:00 MHDA- 2020/05/21 06:00 PMCR- 2019/04/01 CRDT- 2019/03/15 06:00 PHST- 2018/11/15 00:00 [received] PHST- 2019/02/04 00:00 [accepted] PHST- 2019/03/15 06:00 [pubmed] PHST- 2020/05/21 06:00 [medline] PHST- 2019/03/15 06:00 [entrez] PHST- 2019/04/01 00:00 [pmc-release] AID - theoncologist.2018-0787 [pii] AID - ONCO12892 [pii] AID - 10.1634/theoncologist.2018-0787 [doi] PST - ppublish SO - Oncologist. 2019 Apr;24(4):491-497. doi: 10.1634/theoncologist.2018-0787. Epub 2019 Mar 13.