Main Session
Sep 29
SS 40 - Evolving Paradigms in High-Risk Breast Cancer: Optimization and Integration of Treatment Modalities Across the Disease Continuum

318 - Toxicity Results from TBCRC-053 (P-RAD): A Randomized Trial of No, Low or High Dose Preoperative RADiation with Pembrolizumab and Chemotherapy in Node-Positive HER2-Negative Breast Cancer

03:45pm - 03:55pm ET
Room 253

Presenter(s)

Elitza Koutleva, MD, MBA Headshot
Elitza Koutleva, MD, MBA - University of North Carolina at Chapel Hill, Chapel Hill, NC

E. Koutleva1, D. L. Casey1, R. C. Blitzblau2, J. P. Leone3, Y. Abdou4, C. Santa-Maria5, J. Anampa6, A. J. Khan7, J. L. Fox8, S. Dent9, J. L. Wright4, L. Warren10, E. A. Mittendorf11, E. S. Hwang12, L. A. Carey13, S. Patil14, L. Norton15, L. Spring16, A. Y. Ho17, and G. P. Gupta18; 1University of North Carolina, Chapel Hill, NC, 2Duke University Medical Center, Department of Radiation Oncology, Durham, NC, 3Dana Farber, Boston, MA, 4University of North Carolina at Chapel Hill, Chapel Hill, NC, 5Johns Hopkins Hospital, Baltimore, MD, 6Montefiore Einstein Cancer Center, Bronx, NY, United States, 7Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 8Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, 9University of Rochester, Rochester, NY, 10Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, 11Dana Farber Cancer Institute, Department of Breast Surgical Oncology, Boston, MA, 12Duke University, Durham, NC, 13Division of Oncology, University of North Carolina, Chapel Hill, NC, 14Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH, 15Memorial Sloan Kettering Cancer Center, New York, NY, 16Mass General Brigham Cancer Institute, Boston, MA, 17Houston Methodist Academic Institute, Houston, TX, 18UNC, Chapel Hill, NC

Purpose/Objective(s): The safety of administering a preoperative radiotherapy (preop RT) breast tumor boost concurrently with pembrolizumab (pembro) in early-stage breast cancer patients treated with neoadjuvant chemoimmunotherapy followed by breast and lymph node surgery is not well established. The P-RAD trial randomized patients to no-, low-, or high-dose preop RT to the primary tumor with concurrent pembro followed by chemoimmunotherapy to assess whether RT enhances tumor T-cell infiltration and pathologic response in non-irradiated lymph nodes. We herein report general, immune-related, and breast-related toxicities in P-RAD participants.

Materials/Methods: From 2021–2025, 99 patients with cT1c-T4c, cN1-3, cM0 HER2-negative breast cancer and biopsy-proven axillary metastases were randomized to 0 Gy (n=31), 9 Gy (3 Gy x 3, n=34), or 24 Gy (8 Gy x 3, n = 34) preop RT to the breast primary tumor with concurrent pembro. Subsequently, triple-negative breast cancer (TNBC; ER<10%, PR<10%, HER2-negative) patients (n=51) received neoadjuvant pembro with carboplatin, paclitaxel, doxorubicin/hydroxydaunorubicin, and cyclophosphamide (similar to KEYNOTE-522). High-risk hormone receptor–positive (HR+; ER/PR=10%, HER2-negative) patients (n=48) received pembro with paclitaxel, doxorubicin/hydroxydaunorubicin, and cyclophosphamide (similar to KEYNOTE-756). Physician-reported adverse events (AEs) were grouped as general, immune-related, and breast-related. Breast-related AEs included wound complications, dermatitis, chest wall pain, pigmentation changes, skin induration, and dry skin. AEs stratified by grade (³G1, ³G2, ³G3, and G4) in the 9 Gy and 24 Gy arms were compared with 0 Gy using two-tailed Fisher’s exact tests (p<0.05).

Results: No general or immune-related AEs were significantly higher in either 9 Gy or 24 Gy arms versus 0 Gy. Lower rates of ³G1 nausea (42% vs 71%, p=0.02), ³G2 fatigue (21% vs 58%, p=0.002), and ³G1 thyroid abnormalities (3% vs 19%, p=0.05) were observed in the 24 Gy versus 0 Gy arms. Lower rates of ³G2 diarrhea were observed in the 9 Gy vs 0 Gy arms (3% vs 23%, p=0.02). No significant differences in breast-related AEs were observed across arms, the majority of which were G1-G2. G1 or higher wound complication rate was 13% (0 Gy), 15% (9 Gy), and 21% (24 Gy) (p=NS). G3 wound complications occurred in two patients in the 24 Gy arm, and one patient each in the 9 Gy and 0 Gy arms (p=NS). Three G3 chest wall pain events occurred in the 24 Gy arm, while none were observed in the 9 Gy or 0 Gy arms (8.8% vs 0%, p=0.24).

Conclusion: Preop RT at 9 Gy or 24 Gy did not significantly increase general, immune-related, or breast-related AEs in the P-RAD trial. Some toxicities were reduced with preop RT, and ongoing circulating biomarker analyses may help clarify underlying mechanisms. Continued monitoring for chest wall pain after 24 Gy is warranted. (NCT04443348)