Stereotactic body radiation therapy (SBRT) lengthens progression-free survival for patients with advanced lung cancer who have oligoprogression (ie, tumors that have not been fully responsive to systemic chemotherapy or immunotherapy), according to an interim analysis of the CURB oligoprogression trial presented at the 2021 American Society for Radiation Oncology (ASTRO) Annual Meeting.¹ However, the study failed to show a progression-free survival benefit with SBRT in patients with breast cancer who had oligoprogression.

“In this preplanned interim analysis of the first and largest randomized trial of radiotherapy for oligoprogressive metastatic non–small cell lung cancer [NSCLC] and breast cancer, we demonstrated the benefit of SBRT to the sites of oligoprogression on overall progression-free survival, meeting the primary endpoint. The difference in progression-free survival was driven by the substantial response in the lung cancer cohort. The mechanism of the differential benefits between the NSCLC and breast cohorts merits further evaluation,” said lead author C. Jillian Tsai, MD, PhD, Director of Metastatic Disease Radiation Oncology Research at Memorial Sloan Kettering Cancer Center, New York.

C. Jillian Tsai, MD, PhD

Dr. Tsai explained that oligoprogression—or mixed response with limited progression—is an emerging concept in oncology. “Initially all sites of cancer can potentially respond to a given systemic therapy, but over time, it is possible that only a small portion of tumors stop responding, causing a limited number of progressing sites,” she said. It is uncertain whether oligoprogression exists as a unique or temporary state in which tumors are progressing at different rates.

“Currently, there is no standard approach to treating oligoprogressive disease. Some clinicians may switch drugs or choose to add another drug,” she continued. “For oligoprogressive cancers, SBRT may help patients get more mileage out of their current therapy. These patients often have gone through multiple lines of systemic therapy before they get to us. Our study shows they we can selectively use SBRT to treat the sites that are progressing,” explained Dr. Tsai.

The hypothesis of the CURB study was that the addition of radiotherapy specifically targeted to the oligoprogressing sites would prolong stability and enhance progression-free survival.

A total of 106 patients were enrolled in the randomized CURB trial: 59 had NSCLC and 47 had breast cancer. All participants had between one and five progressing metastatic sites that had not responded to systemic therapy; 75% had more than one oligoprogressive site. They were randomly assigned 1:1 to the standard of care (physician’s choice of continuing therapy or switching to another drug), with consideration of SBRT at further disease progression vs upfront SBRT to all progressive sites followed by standard-of-care systemic therapy. Patients were followed for 52 weeks.

Key Findings

For the entire cohort, median progression-free survival was 31 weeks with upfront SBRT vs 11 weeks with the standard of care (P = .002). Patients were followed for a median of 45 weeks. A total of 78% experienced further disease progression, and 39 (37%) died. “This was a threefold difference favoring SBRT in these very sick patients,” Dr. Tsai noted.

In the NSCLC cohort, 40 of 59 patients experienced disease progression. Median progression-free survival was 44 weeks with SBRT vs 9 weeks with the standard of care (P = .001). “The median progression-free survival of 44 weeks is longer than many further lines of systemic therapy,” Dr. Tsai said. There was no significant difference in progression-free survival in the breast cancer cohort: 18 weeks with SBRT vs 19 weeks with the standard of care.

“For the patients with NSCLC, radiation therapy to the oligoprogressive sites tended to help them remain stable and maintain a progression-free state for much longer than with the standard of care. However, for the breast cancer cohort, we didn’t see a difference,” Dr. Tsai emphasized. Median progression-free survival for the breast cancer cohort was 18 weeks with SBRT and 19 weeks with the standard of care. Of the 47 patients, 38 experienced disease progression.

There were slightly more adverse events of grade 2 or higher in the SBRT arm—61% vs 40% in the standard-of-care arm. Grade 2 or higher adverse events occurred in eight patients in the SBRT arm, including one with grade 2 pneumonitis.

Dr. Tsai emphasized that every patient who received SBRT did not experience disease progression in target lesions. New lesions were observed in 45% of the NSCLC cohort and 89.5% of the breast cohort (P < .001). 

DISCLOSURE: Dr. Tsai has served as a consultant for Varian Medical Systems.

REFERENCE

1. Tsai CJ, et al: Consolidative use of radiotherapy to block (CURB) oligoprogression. 2021 ASTRO Annual Meeting. Abstract LBA-3. Presented October 25, 2021.