William P. Harris, MD
The efficacy results of Alliance A021202 suggest that pazopanib is another promising systemic option for carcinoid tumors, according to William P. Harris, MD, Associate Professor of Medicine at the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.
“Progression-free survival was improved by 47%, with a median difference of 3.1 months, and this was statistically significant. The median overall survival did not differ, as it was confounded by a high rate of crossover. Toxicity was expected but notable, though there was no significant difference in quality of life based upon preliminary analysis,” said Dr. Harris, the invited discussant of the study.
“This is the first randomized trial suggesting vascular endothelial growth factor pathway inhibition is a valid target in carcinoids. However, he added, it is important to keep in mind that pazopanib also inhibits other targets, including fibroblast growth factor receptor, which may be of relevance in carcinoid tumors,” Dr. Harris explained. He applauded the investigators for further analyzing the study for potential biomarkers. “Angiome profiling and image analysis are of value as potential predictive markers for tyrosine kinase inhibitors.”
Other Agents Under Study
Pazopanib is also far from the only novel agent being evaluated in the treatment of carcinoid tumors, continued Dr. Harris. Current and future studies are looking at cabozantinib, lenvatinib, ramucirumab, and inhibitors of cyclin-dependent kinases 4/6 (CDK4/6). CDK4 is overexpressed in a large proportion of carcinoid tumors and is amplified in about 20% of neuroendocrine tumors, he noted.
Peptide receptor radionuclide therapy (ie, Lu-177 dotatate) “certainly remains clinically appealing as a second-line option, though it should be optimized,” such as by optimizing dosing or combining peptide receptor radionuclide therapy with systemic therapies, Dr. Harris suggested. The role of immune checkpoint inhibitors, on the other hand, “is less clear,” he said. ■
DISCLOSURE: Dr. Harris has consulted or advised for Bayer, Bristol-Myers Squibb, Eisai, Exelixis, and Neo Therma; has received travel expenses from Eisai; and has received institutional research funding from ArQule, Exelixis, Halozyme, Bristol-Myers Squibb, Eisai, MedImmune, Agios, Bayer, Merck, and BTG.
