Stereotactic ablative radiotherapy (SABR) treatment for oligometastatic or oligoprogressive cancer appeared to come with “acceptable” rates of toxic effects, according to SABR-5 study results.
Among a population of 381 patients in the phase II trial, and with a median follow-up of 25 months, rates of grade 2 or greater toxic effects were observed in 18.6%, with less than 5% of patients experiencing grade 3-5 toxic effects, reported Robert Olson, MD, of the University of British Columbia, and colleagues.
That data indicated that, overall, “SABR in the oligometastatic setting is safe,” they wrote in JAMA Oncology.
But there was one caveat: A single grade 5 toxic effect in a patient with metastatic colon cancer to the liver was possibly tied to SABR. That case “serves as a reminder of the potential toxic effects of this ablative treatment and the need to proceed cautiously and with sufficient level 1 evidence,” Olson’s group stressed. The patient eventually died of recurrent biliary infections associated with the biliary drain, they stated.
Still, SABR-5 “helps to answer a critical question about the safety of treating oligometastases with SABR,” according to Gregory Russo, MD, of the Dartmouth Hitchcock Medical Center in Hanover, New Hampshire, and Michael Katz, MD, of Lowell General Hospital in Lowell, Massachusetts. “This question needs to be answered because of the higher-than-expected rate of grade 5 toxic effects seen in the experimental arm of the SABR-COMET study,” they wrote in an accompanying invited commentary.
SABR-COMET demonstrated a promising survival advantage with SABR, but a concerning rate of high-grade toxic effects (28.8% for grade 2 or higher; 4.5% for grade 5).
Russo and Katz observed that the favorable results of SABR-5 compared with SABR-COMET could be attributed to differences between the studies. For instance, SABR-5 trial had a lower percentage of patients with liver (5% vs 13%) and adrenal (3% vs 6%) metastases treated. Additionally, SABR-5 “used more rigorous lung and nervous system constraints and added rib and chest wall as organs at risk across all dose schedules.”
Olson and colleagues reported grade 2-5 cumulative toxic effects associated with SABR, based on the highest grade toxic effects per patient, were 14.2%, 4.2%, 0%, and 0.3%, respectively. The highest rates of grade 3 or higher toxic effects were seen with liver metastases (10.3%) and adrenal metastases (6.7]). The authors advised these percentages should be considered in the context of a low number for patients for these sites.
They reported that grade 3 or higher toxic effects were less than 5% for the other sites. And the cumulative incidence of grade 2 or higher toxic effects by Kaplan-Meier analysis was 8% at 2 years and 23% at 4 years.
The cumulative incidence of grade 3 or higher toxic effects at those same time points was 4% and 6%, respectively.
The open-label, nonrandomized clinical trial took place at six British Columbia cancer centers. Patients were eligible if they had histologically confirmed cancer, ECOG scores of 0 to 2, a life expectancy of more than 6 months, metastatic disease on imaging, and if they had a primary tumor treated radically, or controlled by prior palliative radiotherapy or systemic therapy, if there were a maximum of five metastases.
Patients had a median age of 68 and 68% were male. Almost a third of the patients had histological findings of prostate cancer (32%), followed by colorectal cancer (17%), breast cancer (11%), and lung cancer (9%). Most patients (69%) had one site treated with SABR, while 22% had two site, and 10% had three or more. The most common sites of SABR were lung (34%), non-spine bone (25%), spine (16%), lymph nodes (14%), liver (5%), and adrenal (3%).
The trial’s primary endpoints were toxic effects assessed by the National Cancer Institute Common Toxicity Criteria version 4 and quality of life measured via patient-reported outcomes. The authors explained that a “reasonable level” of toxic effects associated with SABR was defined a priori as less than 5% grade 5 toxic effects, less than 10% grade 4 toxic effects, and less than 25% grade 3 toxic effects.
Prespecified secondary outcomes included progression-free survival, time from SABR treatment to disease progression at any site or death, and overall survival, with those results to be presented at a future date, they said. That data will be “a critical part of determining the value of SABR in the oligometastatic setting,” said Russo and Katz. “If SABR cannot either improve overall survival or quality of life, perhaps it will be best to rethink its usefulness in treating oligometastatic cancer.”
Study limitations included the fact that, without randomization, it was not possible to determine which proportion of toxic effects described were associated with the SABR interventions versus being part of the natural history of the metastatic disease, or from non-SABR oncological treatments. “The single grade 5 event is a good example of this,” they wrote, pointing out that the study’s toxic effects review committee was split on whether the event was not associated, possibly associated, or probably associated with SABR for the liver.
Olson and his colleagues called their approach to measuring toxic effects “robust,” and said the results support continued enrollment in randomized phase III trials.
SABR-5 was funded by BC Cancer Agency.
Olson disclosed support from, and/or relationships with, Varian Medical Systems, Need, and Novartis.
Russo and Katz disclosed no relationships with industry.