Real-world effectiveness of pazopanib in patients with intermediate prognostic risk advanced renal cell carcinoma (PRINCIPAL study)

Background: Stratification by prognostic risk informs efficacy for various treatments in patients (pts) with advanced renal cell carcinoma (RCC). Whether further stratification beyond prognostic risk aids in predicting treatment outcomes is unknown. We conducted a post-hoc analysis of the real-world PRINCIPAL study (NCT01649778) to assess the effectiveness of pazopanib (PAZ) in pts with intermediate risk advanced RCC. Methods: In this prospective, observational study, pts with advanced and/or metastatic clear cell RCC were enrolled within 30 days of initiating PAZ. Data on progression, survival, and safety were collected approximately every 3 months (mos) until death, consent withdrawal, or loss to follow-up, for up to 30 mos. Primary efficacy end points included overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). A post-hoc analysis of pts with intermediate risk per Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria was conducted to evaluate effectiveness by number or risk factors (1 vs 2), age (<65 vs ≥ 65 years), and Eastern Cooperative Oncology Group performance status (ECOG PS). Results: Of the 657 enrolled pts who received ≥1 dose of PAZ, 363 (55.3%) and 343 (52.2%) had intermediate risk per MSKCC and IMDC criteria, respectively. Within the subgroup of pts with intermediate risk MSKCC and IMDC, median PFS (but not OS) was numerically longer in pts with 1 (vs 2) risk factors, and outcomes were poorer in pts with ECOG PS ≥ 2 (vs < 2) (Table). Median OS within each MSKCC and IMDC risk group was longer than anticipated based on previous clinical trial and real-world data.Table: 884PMedian progression-free survivalMSKCC intermediate risk (n = 363)IMDC intermediate risk (n = 343)Disease progression or death/N (%)Median (95% CI) monthsDisease progression or death/N (%)Median (95% CI) monthsNumber of risk factors*Patients with 1 missing risk factor were excluded.185/147 (57.8)13.8 (10.7-18.1)88/171 (51.5)13.1 (10.7-18.1)285/141 (60.3)7.4 (6.2-10.3)88/133 (66.2)8.1 (6.4-10.7)Age<65 years79/142 (55.6)12.3 (9.0-16.4)73/136 (53.7)13.1 (10.3-18.4)≥65 years131/219 (59.8)10.7 (9.0-13.8)123/205 (60.0)10.7 (9.0-13.1)ECOG PS<2189/333 (56.8)11.2 (9.5-14.1)177/316 (56.0)11.8 (9.9-15.4)≥28/8 (100.0)5.6 (1.3-12.8)8/8 (100.0)2.3 (1.2-10.7)CI; confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; MSKCC, Memorial Sloan Kettering Cancer Center.* Patients with 1 missing risk factor were excluded. Open table in a new tab CI; confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; MSKCC, Memorial Sloan Kettering Cancer Center. Conclusions: The results of the PRINCIPAL study suggest pts with advanced RCC of intermediate prognostic risk can be further stratified to predict treatment outcomes. Clinical trial identification: NCT01649778. Editorial acknowledgement: Editorial support was provided by Chris Ontiveros, PhD (ApotheCom, New York). Legal entity responsible for the study: Novartis Pharmaceuticals Corporation. Funding: Novartis Pharmaceuticals Corporation. Disclosure: G. Procopio: Honoraria: Astellas Pharma, Ipsen Inc., Novartis, Pfizer Inc.; Consulting/advisory roles: Bayer, Bristol-Myers Squibb Company, Ipsen Inc., Novartis Pharma AG, Pfizer Inc. A. Bamias: Personal fees: Novartis Pharma AG, Bristol Meyers Squibb Company, Ipsen Inc. M. Schmidinger: Research funding: Roche Holding AG; Honororia as consulting/advisory role: Pfizer Inc., Roche Holding AG, Bristol-Myers Squibb Company, Ipsen Inc., Novartis Pharma AG, Exelixis; Travel accommodations/expenses: Pfizer Inc., Roche Holding AG, Ipsen Inc. R. Hawkins: Personal fees: BMS, Novartis, Ipsen, EUSA, outside the submitted work; Patent: MRC Phage Antibody with royalties paid. S. Vazquez: Honoraria: Roche Holding AG, Pfizer Inc., Astellas Pharma, AstraZeneca, Bristol-Myers Squibb Company, Sanofi, Eli Lilly and Company; Travel expenses/accommodations: Roche Holding AG, AstraZeneca. N. Srihari: Non-financial support: Janssen. P. Bono: Stockholder: TILT Biotherapeutics; Honoraria: Bristol-Myers Squibb Company, Merck Sharp & Dohme Corp., Orion Corporation, Pfizer Inc., Novartis Pharma AG, Ipsen, Oncorena Holding AB. C. Pisal, Q. Ahmad: Employee of Novartis Pharma AG. Y. Hirschberg: Employee: Novartis Pharma AG; Stockholder: Beckton Dickinson, Novartis Pharma AG. L. Dezzani: Employee and stockholder: Novartis Pharma AG. E. Jonasch: Grants and personal fees: Novartis. All other authors have declared no conflicts of interest.