Grant to fund research on biomarkers for toxicity from prostate cancer radiation

The National Cancer Institute has awarded a $1.8 million grant to investigators at the University of California, Los Angeles (UCLA) Health Jonsson Comprehensive Cancer Center to support the ongoing GARUDA trial (NCT04624256), which is assessing the predictive value of genetic markers in determining which patients are more likely to experience genitourinary (GU) toxicity following radiation therapy for prostate cancer.¹

Completion of the study is anticipated for December 2028.

“Our goal is to improve the post-treatment quality of life for patients with prostate cancer by predicting and preventing the adverse effects of radiation therapy," said principal investigator Amar U. Kishan, MD, in a news release on the study.¹ "This grant will allow us to expand our research and bring us closer to achieving that goal.”

Already, the team of investigators has identified the biomarker PROSTOX, which has shown the ability to predict GU toxicity following advanced radiation therapy. With this grant, the team plans to further validate the predictive value of PROSTOX and other mirSNP genetic markers that have shown promise in predicting toxicity from cancer treatment.

“By understanding the mirSNP genetic markers that predispose patients to adverse side effects from cancer therapy we can tailor these therapies to minimize harm and maximize efficacy. This work has the potential to improve the lives of countless patients,” said co-investigator Joanne B. Weidhaas, MD, PhD, MS, in the news release.¹ Weidhaas is a co-developer of the PROSTOX test as well as a professor of radiation oncology and vice chair and head of translational research at UCLA.

Preliminary data from the GARUDA trial were shared last year at the 2023 American Society of Clinical Oncology Annual Meeting.²

Overall, data showed that 98.8% of patients characterized as low risk for GU toxicity chose to proceed with stereotactic body radiation therapy (SBRT), compared with only 55.2% of patients classified as high risk for toxicity (P < .001). In patients who had over 18 months of follow-up data (n = 57), late GU toxicity greater than grade 2 was observed in 4.8% of patients classified as low risk vs 27.3% of those classified as high risk (P = .015).

In total, the GARUDA trial has enrolled over 200 adult patients with prostate cancer who are eligible to undergo SBRT.³

Patients were excluded from the trial if they presented with neuroendocrine or small cell carcinoma of the prostate, any evidence of distant metastases, or had a history of Crohn disease, ulcerative colitis, or ataxia telangiectasia. Additionally, patients could not have undergone prior whole-gland cryosurgery, high-intensity focused ultrasound, brachytherapy of the prostate, or pelvic radiotherapy.²

All patients included in the study will undergo SBRT per standard of care (SOC), followed by an analysis of germline biomarkers with a non-prospectively validated biomarker panel. Those patients who are determined to be at low risk for toxicity with SBRT will continue to receive SBRT for 14 days. Those determined to have a high risk for toxicity will be counseled to receive either conventionally fractionated radiotherapy over 63 to 70 days, moderate hypofractionated radiotherapy over 28 to 35 days, or to continue to receive SBRT over 14 days per SOC.

The primary outcome measure for the study is the incidence of late-grade 2 or higher physician-score GU toxicity, as assessed for up to 5 years. Secondary outcome measures include 5-year biochemical recurrence-free survival, the rate of acute grade 2 or greater GU and gastrointestinal physician-scored toxicity, and the change in patient-reported urinary, bowel, and sexual quality of life.

Completion of the study is anticipated for December 2028.³

References

1. Radiation oncologists awarded $1.8 million grant to advance personalized cancer therapy. News release. University of California, Los Angeles (UCLA), Health Sciences. July 3, 2024. Accessed July 11, 2024. https://www.newswise.com/articles/view/813586/

2. Weidhaas JB, Marco N, Steinberg ML, et al. Early findings from the GARUDA trial: The impact of a genetic signature of late radiation toxicity on prostate cancer treatment decision making. J Clin Oncol. 2023;41(suppl 16):5089. doi:10.1200/JCO.2023.41.16_suppl.50

3. Germline DNA-based radiosensitivity biomarker influence on toxicity following prostate radiotherapy, GARUDA trial (GARUDA). ClinicalTrials.gov. Last updated March 12, 2024. Accessed July 11, 2024. https://clinicaltrials.gov/study/NCT04624256