Pazopanib combined with best supportive care improves progression-free survival in patients with GIST resistant to imatinib and sunitinib.
—Jean-Yves Blay, MD, PhD
Patients with gastrointestinal stromal tumor (GIST) can achieve remission on tyrosine kinase inhibitors, but almost all of them eventually develop resistance to these agents. The PAZOGIST trial results suggest that pazopanib (Votrient)—a broad-spectrum tyrosine kinase inhibitor—may be an effective option for patients who are resistant to or have disease progression on other tyrosine kinase inhibitors.1
“Pazopanib combined with best supportive care improves progression-free survival in patients with GIST resistant to imatinib [Gleevec] and sunitinib [Sutent],” stated lead author Jean-Yves Blay, MD, PhD, of Centre Léon Bérard, Lyon, France. “Pazopanib deserves further study in this setting.”
Standard therapy is currently imatinib for first-line treatment, sunitinib for the second line, and regorafenib (Stivarga) for the third line. Previously, a small single-arm study in 25 unselected heavily pretreated patients with advanced GIST following failure of at least three treatments, including imatinib and sunitinib, showed “marginal activity [of pazopanib].” In that nonrandomized study, median progression-free survival was 1.9 months.2
PAZOGIST was a larger open-label phase II trial and the first randomized study of pazopanib in patients with advanced or metastatic GIST for whom imatinib and sunitinib therapy had failed. Patients were randomly assigned to receive pazopanib plus best supportive care vs best supportive care alone. In cases of disease progression, patients on the best supportive care arm could cross over to pazopanib.
The primary endpoint was 4-month progression-free survival. Secondary endpoints included overall survival and overall response rates. Dr. Blay presented progression-free survival results at the European Society for Medical Oncology (ESMO) Congress in Madrid.
Four-month progression-free survival was achieved in 47.7% of patients treated with pazopanib vs 19% for those in the best supportive care–alone arm. At the time of this analysis, 36 of 41 patients in the control arm had switched to pazopanib; in this group, after a median of 2.2 months following the switch, median progression-free survival was 3.6 months.
From April 2011 to December 2013, 81 patients were randomly assigned to the two treatment arms. The majority of patients had primary tumors in the small intestine and stomach, more than 90% had mestastatic disease, about 45% had received two prior drugs, while about 55% had had more than two prior treatments. Both treatment arms were well balanced for disease and demographic characteristics.
As would be expected, patients in the pazopanib arm had more adverse events, including gastrointestinal events and deterioration of global health status. ■
Disclosure: Dr. Blay has received research funding and honoraria from GlaxoSmithKline, Novartis, Roche, Pfizer, and Bayer.
1. Blay J, Domont J, Cropet C, et al: A randomized multicentre phase II study of pazopanib plus best supportive care versus best supportive care alone in metastatic gastrointestinal stromal tumors resistant to imatinib and sunitinib. ESMO Congress. Abstract LBA45. Presented September 29, 2014.
2. Ganjoo KN, Villalobos VM, Kamaya A, et al: A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumor following failure of at least imatinib and sunitinib. Ann Oncol 25:236-240, 2014.
Formal discussant of the PAZOGIST trial at the European Society for Medical Oncology (ESMO) 2014 Congress, Stefan Sleijfer, MD, PhD, of Erasmus MC Cancer Institute, Rotterdam, the Netherlands, said “The title of my talk is ‘Small Molecules: Greater Success,’ and we are not yet there.”