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Sequential radiotherapy demonstrated preliminary efficacy and safety as a potential alternative to systemic therapy in patients with oligometastatic renal cell carcinoma.
Sequential radiotherapy demonstrated preliminary efficacy and safety as a potential alternative to systemic therapy in patients with oligometastatic renal cell carcinoma (RCC), according to findings from a phase 2 study (NCT03575611) published in The Lancet Oncology.1,2
The results showed that at a median follow-up of 17.5 months (interquartile range, 13.2-24.6), the median progression-free survival (PFS) was 22.7 months (95% CI, 10.4–not reached [NR]). The 1-year PFS rate was 64% (95% CI, 48%-85%).
“These findings are exciting because we’re challenging the dogma in radiation oncology that RCC is biologically radioresistant,” lead study author Chad Tang, MD, an assistant professor of radiation oncology at The University of Texas MD Anderson Cancer Center, said in a news release.2 “Our strategy to iteratively radiate tumors as they grow and appear has demonstrated promising results. This adds to a growing body of evidence suggesting/indicating radiation therapy could offer an alternative treatment beyond systemic therapy for patients with this disease.”
Regarding the impetus for the study, the role of radiotherapy in metastatic RCC is unclear. To better understand its potential use prior to metastatic disease progression, investigators prospectively evaluated the efficacy and safety of radiotherapy as a means of delaying systemic therapy for patients with oligometastatic RCC.
From July 13, 2018, to Sept 18, 2020, investigators at MD Anderson enrolled 30 adults with 5 or fewer metastatic lesions into the single-arm trial. Women made up 20% (n = 6) of the cohort. All patients had clear cell histology and had a nephrectomy prior to enrollment. Eligible patients had an ECOG performance status of 0 to 2 and were allowed 1 or fewer prior systemic therapies if the therapy was stopped at least 1 month before enrollment.
Patients received 5 or fewer fractions with at least 7 Gy per fraction of stereotactic body radiotherapy (SBRT) to all lesions. If patients could not safely receive SBRT, patients received hypofractionated intensity-modulated radiotherapy regimes consisting of 60 Gy to 70 Gy in 10 fractions or 52.5 Gy to 67.5 Gy in 15 fractions. Additional cycles of radiotherapy were allowed to treat subsequent sites of progression.
“By developing this novel radiation treatment strategy, we sought to shift the treatment paradigm in an effort to provide select RCC patients with a lower-cost, less toxic alternative treatment to systemic therapy,” Tang said.
Feasibility, defined as all planned radiotherapy completed with fewer than 7 days of unplanned breaks, was a co-primary end point with PFS. All efficacy analyses were based on the intention-to-treat population. Safety was analyzed in the treated population.
All patients completed at least 1 round of SBRT with fewer than 7 days of unplanned breaks.
Additional results demonstrated that the 1-year overall survival rate was 100%. Seven (23%) patients started systemic therapy, resulting in a 1-year systemic therapy-free survival probability rate of 82% (95% CI, 70%-98%) and a median systemic therapy-free survival that was not reached (95% CI, 16.1-NR).
Six (20%) patients started systemic therapy for progression, and 1 (3%) started systemic therapy without evidence of progression due to provider choice.
In terms of safety, 3 (10%) patients had severe adverse effects: 2 grade 3 events of back pain and muscle weakness and 1 grade 4 hyperglycemia. There were no treatment-related deaths.
“Given these results, I’m encouraged that serial radiation therapy for oligometastatic RCC has the potential to be practice-changing,” Tang said. “We are giving patients another option for treatment that minimizes the burden of toxicity on the body, while extending survival and maximizing their quality of life. We plan to continue studying this strategy on patients with slightly larger burdens of disease and to analyze biomarkers from these treated patients to improve our ability to select patients who benefit from this treatment.”
Investigators have initiated a second cohort evaluating the feasibility of sequential SBRT alone in patients with low-volume metastatic disease. These data will be reported later.