Patients treated with SBRT had a median PFS of 44 weeks, compared with 9 weeks for those who received standard care.
However, no benefit was observed in patients with metastatic breast cancer. There was no significant difference in PFS between the two groups (18 weeks with SBRT vs. 19 weeks with standard care).
“In this preplanned interim analysis, we demonstrated the benefit of SBRT to sites of oligoprogression on overall progression-free survival, which was the primary endpoint,” said lead author C. Jillian Tsai, MD, PhD, a radiation oncologist and director of metastatic disease radiation oncology research at Memorial Sloan Kettering Cancer Center in New York. “The difference was driven by the substantial response in [this] NSCLC cohort.”
There was no benefit of SBRT seen in the breast cohort, she noted, and most breast patients developed new lesions upon further progression.
Dr. Tsai and colleagues are planning to close the trial early, after the interim analysis established the benefit of SBRT. They are now investigating why SBRT was beneficial in NSCLC but not in breast cancer.
The findings were presented at the American Society for Radiation Oncology (ASTRO) annual meeting.
Dr. Tsai explained that the current standard of care for patients with oligoprogressive metastatic NSCLC is to switch to a different targeted therapy or chemotherapy following progression, but options may be limited. Efficacy for second-line therapy can be poor, with PFS ranging from about 4 months to 10 months for NSCLC, “and after second line, efficacy for third and fourth lines is even poorer,” she said.
Similarly, for breast cancer, PFS ranges from about 9 months to 20 months for estrogen-receptor positive patients. “But for triple negative patients, there really is no standard of care and PFS is poor,” Dr. Tsai said.
SBRT superior to standard of care
The authors hypothesized that there is an oligoprogressive state in metastatic cancer, in which disease control can be improved by applying local therapy to progressive lesions only.
The cohort included 102 patients with metastatic NSCLC or breast cancer who had received one or more lines of systemic therapy and had oligoprogressive lesions amenable to SBRT. There was no upper limit of nonprogressive lesions.
Oligoprogression was defined as Response Evaluation or Positron Emission Tomography Response Criteria in Solid Tumors documented progression ≤5 individual lesions.
Patients were randomly assigned to receive either SBRT to all progressive sites plus palliative standard of care or systemic SOC only. Systemic therapy was per physician’s discretion.
There were 58 patients with NSCLC (30 in the SBRT group) and 44 patients with breast cancer (22 in each group).
Most patients (75%) had more than one site of oligoprogression and 47% had more than 5 total metastatic lesions. About half of patients (54%) had received immunotherapy and the majority of those with NSCLC (86%) did not harbor an actionable driver mutation. About one-third (32%) of the breast cancer cohort were triple negative.
Patients were followed for a median of 45 weeks (58 weeks for living patients), by which time 78 (74%) had experienced further tumor progression and 39 (37%) had died.
Median progression-free survival for the entire cohort was 31 weeks for SBRT and 11 weeks for palliative SOC (P = .002).
In multivariable analysis that stratified for factors including age, sex, lines of systemic therapy, and change of systemic therapy, the progression-free survival benefit of SBRT continued to remain substantial in the NSCLC cohort (hazard ratio: 0.38; P = .007).
Adverse events were higher in the SBRT group. Grade 2 or higher adverse events occurred in 23 (61%) of SBRT patients, and 15 (40%) of SOC patients (P = .13).