Theranostic PET could predict renal cancer progression after therapy

Anti-angiogenic cancer treatments, which suppress the development of new vasculature, have emerged as a powerful way to stop or at least stymie cancer growth in select tumors. A novel PET technique combining a diagnostic radionuclide with a therapeutic agent can now map the potential results of therapy for advanced renal cell carcinoma, according to a study published Dec. 4 in the Journal of Nuclear Medicine. Preliminary results show substantial slowing of disease.

Prior to this study, no known biomarkers have been used to predict the outcome of anti-angiogenic therapy in metastatic renal cell carcinoma. Sjoukje F. Oosting, MD, PhD, from the department of medical oncology at the University Medical Center in Groningen, the Netherlands, and colleagues evaluated Zr-89 bevacizumab as a novel means of mapping likely progression of renal cancer following therapy with either sunitinib or bevacizumab and interferon-a, all of which act to suppress angiogenesis. Bevacizumab is a monoclonal antibody that blocks the growth factor. Within the cell, sunitinib barricades VEGF-receptors, as well as other tyrosine kinases.

“Angiogenesis inhibitors have single-agent activity and double median progression-free survival in patients with metastatic renal cell carcinoma (mRCC),” wrote Oosting et al. “However, not all patients respond, and angiogenesis inhibitors are expensive and can have side effects. Furthermore, studies indicated potential tumor-promoting effects of tyrosine kinase inhibitors (TKIs). Therefore, it is crucial to develop a predictive biomarker for selecting patients who will benefit from these treatments.”

The PET technique rides on the ability to track tumor vascular endothelial growth factor A (VEGF-A), which is thought to be a marker of angiogenesis. The amount of VEGF-A could potentially act as a gauge for angiogenesis and whether or not patients will respond to anti-angiogenic treatments. Researchers measured VEGF-A concentrations by watching uptake of Zr-89 bevacizumab, which goes right to areas of increased blood vessel development.

Results of the study showed differing Zr-89 bevacizumab tumor uptake not only between patients but also in the bodies of individual patients, which may be due to constrasting vascularity, production of VEGF-A and other aspects of tumor biology.

“Patients with intense Z-89 bevacizumab tumor accumulation at baseline had a longer [time to disease progression],” wrote the authors. “This exploratory analysis should be interpreted with caution, but may indicate that those tumors are more VEGF driven and dependent and therefore can be effectively controlled with anti-angiogenic treatment.

A pitched baseline tumor uptake may have been linked to prolonged periods without disease progression, but, interestingly, bevacizumab and interferon-a together led to lower uptake of Zr-89, and tracer uptake fell flat initially in patients receiving sunitinib, but uptake picked up again two weeks after therapy.

For this study, 22 patients had PET scans before therapy, two weeks after start of therapy, and then six weeks after the start of therapy with either bevacizumab every two weeks with interferon-a or daily sunitinib for four weeks in a six week cycle.

A total of 125 tumor lesions were revealed by Zr-89 bevacizumab PET with a median standard uptake value maximum (SUVmax) of 6.9. That measurement plummeted about 47 percent with the combined bevacizumab and interferon-a treatment and again 9.7 percent at second scanning. Treatment with sunitinib dipped the SUVmax 14.3 percent until the six-week mark, when it pitched to 72.6 percent. SUVmax was not strongly linked to plasma VEGF-A at all times. Overall, the longest periods free of disease progression were associated with a baseline mean tumor SUVmax greater than a 10 in three major lesions. This scenario led to 89.7 progression-free weeks vs. 23 weeks.

More research, including a randomized trial, will be needed to figure out how predictive, and prognostic, baseline Zr-89 bevacizumab tumor uptake really is for patients with advanced renal cell carcinoma.