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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Thursday, April 25, 2024
According to Julia Tchou, MD, PhD, of the University of Pennsylvania, Wayne, and colleagues, high preexisting T-cell receptor repertoire diversity may predict responses to preoperative treatment with radiotherapy plus the immune checkpoint inhibitor pembrolizumab in patients with early-stage breast cancer. The preliminary results of their study were presented during the 2024 Society of Surgical Oncology (SSO) Annual Meeting (Abstract 8).
A total of 19 patients with 21 evaluable tumors were either administered 7 Gy of radiotherapy in a single fraction before (arm 1) or after (arm 2) receiving a single dose of pembrolizumab, or they were treated with pembrolizumab alone (arm 3). The median age of the participants was 57 years, of whom 12 were White, 5 were Black, and 2 were Hispanic Black. A total of 14 patients had triple-negative disease; 6 had hormone receptor–positive, HER2-negative disease and 1 had HER2-positive disease. The investigators defined a clinically significant treatment response as reduction in tumor size of more than 30%.
Overall, 43% of tumors exhibited a clinically significant treatment response. This rate was found to be significantly higher in arms 1 and 2 vs 3 (60% vs 0%; P = .0143). Treatment sequence did not appear to impact the likelihood of achieving such an outcome (arm 1 vs 2, 55% vs 60%; P = .862). Based on correlative analyses, in peripheral blood mononuclear cells, higher preexisting T-cell receptor repertoire diversity was significantly associated with a clinically significant treatment response (P = .035). No adverse events of higher than grade 2 were reported.
“The impact of preoperative [radiotherapy plus immune checkpoint inhibition] on long-term outcomes remains undefined,” the investigators concluded. “Future work to unravel the local and systemic immunologic consequences in this and other window-of-opportunity studies may provide a rational approach and framework to de-escalate immunotherapy in select patients.”
Disclosure: For full disclosures of the study authors, visit sso2024.eventscribe.net.
