Metastatic kidney cancer is largely an incurable disease. Despite recent advances, most patients eventually succumb to the disease. Resistance develops to each line of therapy, which is followed by the next with progressively lower returns, and some patients run out of drugs.
With one exception, little is known about how drug resistance arises. There is equally little understanding about patterns of progression. For example, while progression occurs at multiple sites in some patients, only a few growing sites are observed in others.
“Current standard of care for metastatic progression is to change systemic (drug) therapy,” said lead author Raquibul Hannan, M.D., Ph.D., Associate Professor of Radiation Oncology and KCP Radiation Oncology Co-Leader, “but there’s no guarantee the next line of therapy will be effective.”The KCP study found that highly focused stereotactic ablative radiation (SAbR) was an effective strategy for controlling metastatic disease when it progresses at just a few sites, known as oligoprogression. The phase 2 clinical trial showed that SAbR extended ongoing systemic therapy by a median of 11.1 months.
Stereotactic ablative radiation (SAbR) control of isolated progressive metastasis in kidney cancer clinical trial.
Involving multiple institutions across the country, the Canadian study, also a phase 2 trial, showed similar results with SAbR extending systemic therapy by 12.6 months.
Both studies deployed sequential SAbR over time while the disease remained oligoprogressive, which is a new approach, and both showed that SAbR successfully controlled radiated lesions (>90% local control rates). Additionally, the KCP study showed that SAbR did not undermine patients’ quality of life.
These findings build on a pioneering report from KCP investigators published in 2013, and retrospective studies by KCP and other investigators showing promise of SAbR for oligoprogression.
Localized therapies such as SAbR, which are generally associated with minimal toxicity, are an attractive option to complement systemic therapies that are otherwise working and well tolerated. For those who respond to systemic therapy, the development of a few “rogue” drug-resistant metastases may not demand a change of treatment. Eradicating progressing sites with high-dose, pinpoint radiation may extend the window where drugs can provide effective cancer control.
“While both clinical trials involved a small number of patients, the concordant positive results suggest that the approach has merit. These studies support larger trials that may introduce SAbR in routine patient care,” said co-corresponding author James Brugarolas, M.D., Ph.D., Professor of Internal Medicine, Division of Hematology and Oncology, and Director of the KCP.
Dr. Brugarolas holds the Sherry Wigley Crow Cancer Research Endowed Chair in honor of Robert Lewis Kirby, M.D.
Other UT Southwestern researchers who contributed to this study include Robert Timmerman, M.D.; Hans Hammers, M.D., Ph.D.; Michael Christensen, M.D.; Alana Christie, M.S.; Brendan Paulman, B.A.; Aurelie Garant, M.D.; Waddah Arafat, M.D.; Kevin Courtney, M.D., Ph.D.; Suzanne Cole, M.D.; David Sher, M.D.; Chul Ahn, Ph.D.; and Hak Choy, M.D.
This work was supported by grants from NIH (P50CA196516) and the American Cancer Society (RSG-16-004-01-CCE). The clinical trial was funded by the UTSW Department of Radiation Oncology and UTSW.
The authors declare no relevant conflicts of interest.
Source: "Clinical Trial Shows Stereotactic Radiation Extends Systemic Therapy And Slows Kidney Cancer Progression". 2022. UT Southwestern Medical Center.