Niraparib and Dostarlimab Show Promise in BRCA-Mutated, ER-Positive, HER2-Negative Breast Cancer
核心洞察
A phase 2 trial (TBCRC-056) evaluated neoadjuvant niraparib plus dostarlimab in patients with germline BRCA (搜索)-mutated, ER (搜索)-positive, HER2 (搜索)-negative breast cancer (搜索), showing promising responses.
The pathological complete response (pCR) rate was 16.7%, and 44.4% of patients achieved a residual cancer burden (RCB) score of zero or 1, indicating a substantial reduction in cancer burden.
The combination therapy was generally well-tolerated, with the most common grade 3 treatment-related side effects being rash (27.8%) and increased alanine transaminase levels (16.7%).
A combination of Zejula (niraparib) and Jemperli (dostarlimab-gxly) has demonstrated promising responses in a subset of breast cancer (搜索) patients, according to data from group C of the phase 2 TBCRC-056 trial presented at the 2024 San Antonio Breast Cancer Symposium. The study focused on patients with germline BRCA (搜索)-mutated estrogen receptor (ER (搜索))-positive, HER2 (搜索)-negative breast cancer.
The trial, led by Dr. Erica L. Mayer from Dana-Farber Cancer Institute, enrolled patients with stage 1 to 3, HER2 (搜索)-negative breast cancer (搜索) with germline BRCA1/2 or PALB2 mutations. In group C, 18 patients received neoadjuvant treatment with Zejula (200 mg orally daily) and Jemperli (500 mg intravenously every three weeks) for 18 weeks.
The results showed a pathological complete response (pCR) rate of 16.7%. Additionally, 44.4% of patients achieved a residual cancer burden (RCB) score of zero or 1. Specifically, 27.8% had an RCB score of 1, 22.2% had an RCB score of 2, and 22.2% had an RCB score of 3. Two patients required additional neoadjuvant therapy, with an 11.1% response rate in this subgroup.
The median patient age was 41.8 years, with 77.8% being White. Most patients had stage 2 disease (44.4%) at diagnosis, followed by stage 1 (38.9%) and stage 3A (16.7%). The majority of patients had a tumor grade of 2 (61.1%). A germline BRCA1 mutation was observed in 27.8% of patients, while 72.2% had a BRCA2 mutation.
Regarding treatment exposure, all 18 patients completed therapy and underwent surgery. Before surgery, two patients received additional neoadjuvant therapy, 83.3% completed six cycles of Zejula, and 61.1% completed six cycles of Jemperli.
The most common grade 3 treatment-related adverse events included rash (27.8%), increased alanine transaminase levels (16.7%), and nausea (5.6%).
Dr. Mayer noted the significance of these findings, stating, "Given the activity of preoperative PD-1 inhibition for ER (搜索)-positive breast cancer (搜索), additional evaluation of targeted non-chemotherapy approaches is of great interest in this patient population."
While previous data suggested that adding an anti-PD-L1 therapy to a PARP inhibitor did not increase activity in patients with BRCA (搜索)-mutated breast cancer (搜索), Dr. Mayer suggested that there may be room for this combination in less immunosuppressed early-stage settings. She concluded, "Additional exploration of the immunosuppressive components of the tumor microenvironment may help fully realize the impact of combining immunologic approaches with PARP inhibition."