KEY TAKEAWAYS
- The phase II trial aimed to investigate the immune-based therapies that boost T cell-killing activity for brain metastases.
- The study’s primary endpoint was complete response, partial response, or stable disease with pembrolizumab treatment.
- The study found that pembrolizumab effectively treated brain metastases and may be a promising treatment option for this patient population.
Brain metastases are difficult to treat as they have a tumor microenvironment that suppresses the immune system. Immune-based therapies that boost T cell-killing activity are a promising approach to treating brain metastases. Researchers aimed to investigate the immune-based therapies that boost T cell-killing activity for brain metastases.
The study enrolled 58 pts to ensure at least 52 were evaluable (i.e., received at least one dose of pembrolizumab). The primary endpoint was to assess the intracranial benefit, defined as the best response of complete response, partial response, or stable disease per RANO criteria during treatment. The study aimed to compare a null intracranial benefit rate of 10% with an alternative rate of 24%. Meeting the primary endpoint required at least 8 pts out of the 52 to show intracranial benefit, indicating pembrolizumab’s potential for further study in this patient group. This design had a 10% type-I error and 89% power with a target type-II error of 15%.
Of 57 pts, the median age was 53 (range 28-80), with 81% female. Tumor types varied, including breast (n = 35), non-small cell lung cancer (n = 7), melanoma (n = 2), small-cell lung cancer (n = 2), sarcoma (n = 2), and several others. There were 16 HER-2-positive, 17 hormone receptor-positive, and 11 triple-negative cases among breast cancer patients(pts). The study met its primary endpoint with an intracranial benefit rate of 42.1% (90% CI: 31-54%). About 7 pts with breast cancer, melanoma, or sarcoma showed long-lasting intracranial anti-tumor activity (> 2 years). The extracranial benefit rate was 45% (18/40; 90% CI: 31-59%) in pts with assessable extracranial disease per RECIST 1.1 criteria. Median overall survival(OS) was 8.0 months (90% CI: 5.5-8.7 months). Two cases of grade 4 toxicities possibly related to treatment (cerebral edema) and 13 pts stopped treatment due to adverse events (AEs).
The study found that pembrolizumab effectively treated brain metastases and may be a promising treatment option for this patient population.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.2006
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02886585
Priscilla Kaliopi Brastianos, Albert Eusik Kim, Anita Giobbie-Hurder, Eudocia Quant Lee, Nancy U. Lin, Beth Overmoyer, Patrick Y. Wen, Lakshmi Nayak, Justine Vanessa Cohen, Jorg Dietrich, Rebecca Suk Heist, Ian E. Krop, Donald P. Lawrence, Erica L. Mayer, Eric P. Winer, Helen Alice Shih, Kevin S. Oh, Daniel P. Cahill, Elizabeth R Gerstner, Ryan J. Sullivan, and DF/HCC 16-153 Brain Metastasis Team. DOI: 10.1200/JCO.2023.41.16_suppl.2006 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 2006-2006.
