Article Impact Level: HIGH Data Quality: STRONG Summary of Journal of Clinical Oncology, 42(36), 4282–4293. https://doi.org/10.1200/JCO.24.00003 Dr. Alice Y. Ho et al.
Points
- Preoperative radiation therapy (RT) with pembrolizumab led to high pathologic complete response (pCR) rates—59.2% in triple-negative breast cancer (TNBC), 33.3% in HR+/HER2–, and 54.5% overall.
- The 3-year event-free survival (EFS) rate was 80%, suggesting long-term benefits of the treatment combination.
- Grade ≥3 toxicities occurred in 41% of patients, indicating a need for careful monitoring despite the therapy’s efficacy.
- PD-L1 levels rose significantly after both pembrolizumab alone and pembrolizumab with RT, suggesting its potential as a predictive biomarker.
- TNBC patients saw a decrease in TILs after adding RT, highlighting the importance of treatment sequencing in optimizing immune response.
Summary
This phase I/IIb trial assessed the safety and immune biomarkers following preoperative radiation therapy (RT) combined with pembrolizumab (anti-PD1 therapy) in patients with triple-negative breast cancer (TNBC) and hormone receptor-positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) breast cancer. A total of 66 patients were enrolled, with 54 having TNBC and 12 having HR+/HER2– breast cancer. The treatment protocol involved pembrolizumab followed by RT (24 Gy/three daily fractions) targeting the breast tumor, followed by neoadjuvant chemotherapy (NAC). Coprimary endpoints included safety and the change in tumor-infiltrating lymphocytes (TILs), while secondary endpoints included pathologic complete response (pCR), residual cancer burden (RCB), and event-free survival (EFS).
The results showed that % incidence of grade ≥3 toxicities was 41%. Pathologic complete response rates were 59.2% for TNBC, 33.3% for HR+/HER2–, and 54.5% for the entire cohort. Near pCR (RCB 0-1) was observed in 77.8% of TNBC patients and 41.6% of HR+/HER2– patients. The 3-year EFS rate was 80%. Biomarker analysis showed an increase in PD-L1 expression after both anti-PD1 (median Combined Positive Score [CPS], 7.49-23.20; 95% CI, –41.88 to –6.30; P = .044) and anti-PD1/RT (median CPS, 7.49-23.41; 95% CI, –41.88 to –6.30; P = .009) compared to baseline. In TNBC patients, adding RT to anti-PD1 significantly reduced TILs (28.9% to 17.1%, 95% CI, 2.46 to 21.09; P = .014).
In conclusion, preoperative RT combined with pembrolizumab is safe, leading to high pCR rates and a favorable 3-year EFS. The findings suggest that PD-L1 expression and TILs could be predictive biomarkers for preoperative anti-PD1/RT response. The observed reduction in TILs with the addition of RT emphasizes the importance of treating sequentially to optimize outcomes.
Link to the article: https://ascopubs.org/doi/10.1200/JCO.24.00003
References Ho, A. Y., Shiao, S., Kobald, S. A., Chen, J., Duda, D. G., Ly, A., Bossuyt, V., Cho, H. L., Arnold, B., Knott, S., Gupta, G. P., McAndrew, P., Karlan, S., Tighiouart, M., Muzikansky, A., Basho, R., & McArthur, H. (2024). Pearl: A phase ib/ii biomarker study of adding radiation therapy to pembrolizumab before neoadjuvant chemotherapy in human epidermal growth factor receptor 2–negative breast cancer. Journal of Clinical Oncology, 42(36), 4282–4293. https://doi.org/10.1200/JCO.24.00003
