Stereotactic ablative radiation shows promise in patients with oligoprogressive mRCC

A new study has found that patients with oligoprogressive metastatic renal cell carcinoma (mRCC) who underwent stereotactic ablative radiation (SAbR) showed prolonged responses to ongoing systemic therapy.^1,2

At a median follow-up of 10.4 months (IQR: 5.8-16.4), SAbR extended drug efficacy by more than 6 months in 70% of mRCC patients (14 out of 20; 95% CI: 49.9-90.1).

Another recently published phase 2 trial³ yielded similar findings, “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),” according to a news release about the findings.

Raquibul Hannan, MD, PhD

“Current standard of care for metastatic progression is to change systemic (drug) therapy, but there’s no guarantee the next line of therapy will be effective,” said lead author Raquibul Hannan, MD, PhD, chief of the Genitourinary Radiation Oncology Service at the University of Texas (UT) Southwestern Medical Center in Dallas, in the news release.

The UT Southwestern study was a single-arm phase 2 clinical trial that enrolled 20 patients from February 2019 to October 2020, who demonstrated overall disease control during first- to fourth-line systemic therapy with progression at 3 or fewer sites in 30% or fewer of all sites. All patients were at least 18 years old with pathology-proven RCC and an Eastern Cooperative Oncology Group (ECOG) score of 1-2. The study excluded high-risk patients using International Metastatic RCC Database Consortium (IMDC) criteria.

Clinicians delivered rounds of SAbR therapy through on-board cone beam CT, in which dosing regimens included at least 25 Gy × 1 fraction, at least 12 Gy × 3 fractions, or at least 8 Gy × 5 fractions to cover more than 95% of the target volume. Patients were administered SAbR and monitored at either UT Southwestern’s Harold C. Comprehensive Cancer Center or the Parkland Health and Hospital System.

At initial SAbR, 60% of patients (12 out of 20) had synchronous metastases and 55% of patients (11 out of 20) had 1 lesion treated. Additionally, 12 patients had 6 or more initial sites of disease and 8 patients had 5 or fewer sites. There were 37 total treated lesions, 29 of which were upfront and 8 of which were treated subsequently. The median size of initial lesions with SAbR was 3.4 cm (IQR: 2.4-4.9 cm).

Results showed that the median time from SAbR treatment to either a new systemic therapy or death was 11.1 months (95% CIL 4.5-19.3), the median duration of SAbR-aided systemic therapy was 24.4 months (95% CI: 15.3-42.2), and the median overall survival was not reached. Although 1 patient developed grade 3 gastrointestinal toxicity that could have been related to SAbR, there was no significant decline in quality of life of the overall patient population.

James Brugarolas, MD, PhD

“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, MD, PhD, professor of internal medicine in the division of hematology and oncology and director of the Kidney Cancer Program at UT Southwestern Medical Center.

References

1. Hannan R, Christensen M, Hammers H, et al. Phase II trial of stereotactic ablative radiation for oligoprogressive metastatic kidney cancer. Eur Uro Onc. Published online January 2, 2022. doi:10.1016/j.euo.2021.12.001

2. Clinical trial shows stereotactic radiation extends systemic therapy and slows kidney cancer progression. News release. University of Texas Southwestern Medical Center. January 3, 2022. Accessed January 4, 2022. https://www.utsouthwestern.edu/newsroom/articles/year-2022/stereotactic-radiation-extends-systemic-therapy.html

3. Cheung P, Patel S, North SA, et al. Stereotactic radiotherapy for oligoprogression in metastatic renal cell cancer patients receiving tyrosine kinase inhibitor therapy: a phase 2 prospective multicenter study. Eur Urol 2021;80(6):693-700. doi:10.1016/j.eururo.2021.07.026