ESMO 2018: PRINCIPAL Study - Real-World Effectiveness of Pazopanib in Patients with Intermediate Prognostic Risk Advanced Renal Cell Carcinoma

Munich, Germany ( Pazopanib is a multikinase inhibitor which limits tumor growth via inhibition of angiogenesis by inhibiting VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α, PDGFR-β, FGFR-1, FGFR-3, cKIT, interleukin-2 receptor inducible T-cell kinase, lymphocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms)1. In a phase III trial, pazopanib was shown to be superior to placebo in both treatment naïve and cytokine-pretreated patients with advanced or metastatic RCC2. In another phase III trial (COMPARZ), pazopanib was compared with sunitinib and shown to be noninferior in terms of progression-free survival (1.05; 95% confidence interval [CI], 0.90 to 1.22) and had similar overall survival as well compared with sunitinib (hazard ratio for death with pazopanib, 0.91; 95% CI, 0.76 to 1.08)3. The PRINCIPAL study was conducted as a global, multicenter, prospective, observational study (VEG115232, NCT01649778) evaluate the real-world effectiveness and safety of pazopanib in patients with advanced or mRCC4.

UroToday ESMO2018 PRINCIPLE Study

This abstract provides data on 657 patients who have received one or more doses of pazopanib in the real world, outside of clinical trials. About 75% of patients have completed follow up. In terms of baseline characteristics, 70% were men, mostly white (95%), and were initiated on therapy very shortly after diagnosis (median 1.8 months). Most patients had lung metastases (66%), followed by lymph nodes (32%) and bone (25%). Almost all patients had prior nephrectomy (79%).

In terms of response, 34% of patients with MSKCC intermediate risk and 33% of patients with IMDC intermediate risk had an objective response. There were 0 responses in patients with an ECOG of 2 or more, although the absolute number here was low (7 patients). Median duration of therapy was much longer for patients with 1 risk factor than 2 risk factor in both risk classifications.

UroToday ESMO2018 PRINCIPLE Study 2

The median progression-free survival (PFS) was 12.3-13.1 months for those under 65 years old and 10.7 months for those older than 65. As expected, PFS was worse in patients with more risk factors, older, worse ECOG performance status.  In terms of overall survival, patients with one risk factor had a median overall survival of 33.9 months compared to 19.4 months for those with 2 risk factors. 

UroToday ESMO2018 PRINCIPLE Study 3
The most common treatment-related adverse events were hypertension, diarrhea, elevated liver enzymes, hypothyroidism, and nausea.  The side effect profile was similar for patients older and younger than 65.

For most intermediate-risk patients, progression-free survival ranges from 7 months – 13 months, unless they have poor performance status.  This compares favorably to the 8.4 months which was described in COMPARZ. For patients with poor performance status, pazopanib does not provide significant benefit.

Presented by: Giuseppe Procopio, MD, Professor, Medical Oncology, National Cancer Institute of Milan, Italy

1. Hurwitz H, Dowlati A, Savage S, et al. Safety, tolerability and pharmacokinetics of oral administration of GW786034 in pts with solid tumors. Journal of Clinical Oncology 2005;23:3012-.
2. Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial. Journal of Clinical Oncology 2010;28:1061-8.
3. Motzer RJ, Hutson TE, Cella D, et al. Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma. New England Journal of Medicine 2013;369:722-31.
4. Bamias A, Bono P, Procopio G, et al. Principal: A prospective observational study of real-world treatment patterns and treatment outcomes in patients with advanced or metastatic renal cell carcinoma (mRCC) receiving pazopanib. Journal of Clinical Oncology 2014;32:TPS4600-TPS.

Written By: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, Twitter: @TheRealJasonZhu at the 2018 European Society for Medical Oncology Congress (#ESMO18), October 19-23,  2018, Munich Germany