SBRT Plus Standard of Care Improves PFS in Oligoprogressive NSCLC

SBRT Plus Standard of Care Improves PFS in Oligoprogressive NSCLC

Patients with oligoprogressive non–small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SBRT) plus standard-of-care therapy experienced improvements in progression-free survival (PFS) vs standard of care alone, as shown in results from the phase 2 Consolidative Use of Radiotherapy to Block (CURB) trial (NCT03808662).

Of note, this benefit was not observed in patients with oligoprogressive breast cancer.

In the full patient population with oligoprogressive metastatic NSCLC and breast cancer, standard of care alone produced a median PFS of 3.2 months (95% CI, 2.0-4.5) compared with 7.2 months (95% CI, 4.5-10.0) using SBRT plus standard of care (HR, 0.53; 95% CI, 0.35-0.81; P = .0035). For patients with NSCLC, the median PFS was 2.2 months (95% CI, 2.0-4.5) vs 10.0 months (95% CI, 7.2-not reached [NR]) in each respective arm (HR, 0.41; 95% CI, 0.22-0.75; P = .0039). Additionally, the median PFS in each respective arm was 4.2 months (95% CI, 1.8-5.5) vs 4.4 months (95% CI, 2.5-8.7) among those with oligoprogressive breast cancer (HR, 0.78; 95% CI, 0.43-1.43; P = .43).

A multivariate analysis adjusting for number of oligoprogressive sites of metastasis, receptor or driver genetic alteration status, primary site, and type of prior systemic therapy highlighted a consistent PFS benefit with SBRT plus standard of care in patients with NSCLC (HR, 0.33; 95% CI, 0.16-0.66; P = .0019) but not those with breast cancer (HR, 0.79; 95% CI, 0.37-1.65; P = .40). Additionally, the addition of SBRT to standard of care did not confer an overall survival (OS) benefit across the entire cohort (HR, 0.99; 95% CI, 0.55-1.81; P = .40) or disease-specific subgroups.

“The observed clinical outcomes and genomic alterations provide compelling evidence of the identification of oligoprogression in patients with metastatic NSCLC, who could therefore benefit from local ablative therapy,” the study authors wrote. “This finding differed from the systemic progression observed in patients with breast cancer, highlighting the limitations of the current radiographic definition of oligoprogression when selecting patients with metastatic breast cancer for local therapy. The results from this study might also indicate that there is no discernible oligoprogression in metastatic breast cancer, presenting a challenge in identifying and effectively treating these patients with local therapy.”

In the open-label CURB trial, 106 patients were randomly assigned to receive standard-of-care therapy alone (n = 51) or in combination with SBRT (n = 55). Most radiotherapy regimens ranged from 27 to 30 Gy in 3 fractions or 30 to 50 Gy in 5 fractions.

The trial’s primary end point was PFS for up to 12 months. Secondary end points included OS, toxicity, and quality of life (QOL).

Patients 18 years and older with metastatic disease determined via imaging and histologically confirmed breast cancer or NSCLC were able to enroll on the trial. Additional eligibility criteria included having prior treatment with frontline systemic therapy, extracranial oligoprogression based on RECIST or PERCIST guidelines, and potential for all oligoprogressive sites to be safely managed.

Overall, 28 and 31 patients with NSCLC, respectively, were assigned to the standard-of-care arm and SBRT arm; 23 and 24 patients with breast cancer were assigned to each respective arm. Anywhere from 71% to 83% of patients had 2 to 5 oligoprogressive lesions, and 70% to 87% of patients had no brain metastases. In the standard-of-care and SBRT arms, respectively, a higher proportion of patients with NSCLC received immunotherapy (82% and 77%) compared with those who had breast cancer (17% vs 25%). Most patients with NSCLC had no driver mutations in each respective arm (89% vs 84%), and most of those with breast cancer had non–triple-negative disease (61% vs 71%).

Grade 2 or higher adverse effects (AEs) affected 41% of those who received standard of care alone and 62% of those who received SBRT plus standard of care. The most common grade 2 or higher toxicities in each respective arm included lymphocyte count decreases (20% vs 41%), anemia (12% vs 29%), and neutrophil count decreases (12% vs 22%).

Overall, QOL scores were comparable between treatment arms, although a decline in QOL scores was highlighted among those in the standard-of-care arm at week 36. These declines included global health status, physical functioning, and social functioning scores. Investigators noted that these declines may have been impacted by the small sample size at 36 weeks, making it difficult to conduct a statistical comparison between arms at this time.

Reference

Tsai CJ, Yang JT, Shaverdian N, et al. Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study. Lancet. 2024;403:171-182. doi:10.1016/S0140-6736(23)01857-3