Giuseppe Procopio1, Aristotelis Bamias2, Manuela Schmidinger3, Robert Hawkins4, Angel Rodriguez Sánchez5, Sergio Vázquez Estevez6, Narayanan Srihari7, Haralabos Kalofonos8, Petri Bono9, Chaitali Babanrao Pisal10, Yulia Hirschberg11, Luca Dezzani11, Qasim Ahmad11, Cristina Suárez Rodriguez12, Eric Jonasch13. 1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: giuseppe.procopio@istitutotumori.mi.it. 2. Department of Clinical Therapeutics, National and Kapodistrian University of Athens Alexandra Hospital, Athens, Greece. 3. Department of Medicine, Medical University of Vienna, Vienna, Austria. 4. The Christie NHS Foundation Trust, Christie CRC Research Centre, Manchester, UK. 5. University Hospital of Leon, Campus de Vegazana, León, Spain. 6. Department of Oncology, Hospital Universitario Lucus Augusti, Lugo, Spain. 7. Department of Oncology, Shrewsbury & Telford Hospitals NHS Trust, Shrewsbury, UK. 8. Division of Oncology, Department of Medicine, University of Patras, Panepistimioupoli Patron, Patra, Greece. 9. Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland. 10. Novartis Healthcare Private Limited, Salarpuria-Sattva Knowledge City, Raidurg, Hyderabad, India. 11. Novartis Pharmaceuticals Corporation, East Hanover, NJ. 12. Department of Oncology, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Centro Cellex, Barcelona, Spain. 13. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Abstract
INTRODUCTION: The objective of this study was to determine the effectiveness and safety of pazopanib in patients with intermediate-risk advanced/metastatic renal cell carcinoma in the PRINCIPAL study (NCT01649778). PATIENTS AND METHODS: Patients had clear-cell advanced/metastatic renal cell carcinoma and met intermediate-risk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Assessments included progression-free survival, overall survival, objective response rate, and safety. We also evaluated effectiveness based on number of risk factors, age, and performance status (PS), as well as safety in older and younger patients. RESULTS: Three hundred sixty three and 343 intermediate-risk MSKCC and IMDC patients were included, respectively. The median progression-free survival was 13.8 months (95% confidence interval [CI], 10.7-18.1 months) and 7.4 months (95% CI, 6.2-10.3 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 13.1 months (95% CI, 10.7-18.1 months) and 8.1 months (95% CI, 6.4-10.7 months) for patients with 1 and 2 IMDC risk factors, respectively. The median overall survival was not reached and was 15.2 months (95% CI, 12.3-26.5 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 33.9 months (95% CI, 33.9 months to not estimable) and 19.4 months (95% CI, 14.3 months to not estimable) with 1 and 2 IMDC risk factors, respectively. A lower overall response rate was observed with Eastern Cooperative Oncology Group PS ≥ 2 (vs. PS < 2). All-grade treatment-related adverse events occurred in approximately 63% of patients, and the safety profile among older and younger patients was similar. CONCLUSIONS: Outcomes with pazopanib in intermediate-risk patients suggest that patients can be further stratified by number of risk factors (1 vs. 2) and Eastern Cooperative Oncology Group PS (< 2 vs. ≥ 2) to more accurately predict outcomes.
INTRODUCTION: The objective of this study was to determine the effectiveness and safety of pazopanib in patients with intermediate-risk advanced/metastatic renal cell carcinoma in the PRINCIPAL study (NCT01649778). PATIENTS AND METHODS: Patients had clear-cell advanced/metastatic renal cell carcinoma and met intermediate-risk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Assessments included progression-free survival, overall survival, objective response rate, and safety. We also evaluated effectiveness based on number of risk factors, age, and performance status (PS), as well as safety in older and younger patients. RESULTS: Three hundred sixty three and 343 intermediate-risk MSKCC and IMDC patients were included, respectively. The median progression-free survival was 13.8 months (95% confidence interval [CI], 10.7-18.1 months) and 7.4 months (95% CI, 6.2-10.3 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 13.1 months (95% CI, 10.7-18.1 months) and 8.1 months (95% CI, 6.4-10.7 months) for patients with 1 and 2 IMDC risk factors, respectively. The median overall survival was not reached and was 15.2 months (95% CI, 12.3-26.5 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 33.9 months (95% CI, 33.9 months to not estimable) and 19.4 months (95% CI, 14.3 months to not estimable) with 1 and 2 IMDC risk factors, respectively. A lower overall response rate was observed with Eastern Cooperative Oncology Group PS ≥ 2 (vs. PS < 2). All-grade treatment-related adverse events occurred in approximately 63% of patients, and the safety profile among older and younger patients was similar. CONCLUSIONS: Outcomes with pazopanib in intermediate-risk patients suggest that patients can be further stratified by number of risk factors (1 vs. 2) and Eastern Cooperative Oncology Group PS (< 2 vs. ≥ 2) to more accurately predict outcomes.