2 Clarke Drive
Suite 100
Cranbury, NJ 08512
© 2025 MJH Life Sciences™ and OncLive - Clinical Oncology News, Cancer Expert Insights. All rights reserved.
Neoadjuvant niraparib plus dostarlimab led to pathologic complete responses in BRCA- or PALB2-mutated triple-negative breast cancer.
Neoadjuvant niraparib (Zejula) in combination with dostarlimab-gxly (Jemperli) generated pathological complete response (pCRs) in patients with stage I to III triple-negative breast cancer (TNBC) harboring BRCA or PALB2 mutations, according to data from the phase 2 TBCRC-056 trial (NCT04584255) presented at the 2025 San Antonio Breast Cancer Symposium.1
Findings demonstrated that evaluable patients (n = 46) achieved a pCR/residual cancer burden 0 (RCB-0) rate of 50.0% (90% CI, 37.1%-62.9%) at the time of surgery. These rates were 50.0% in arm A (n = 22), where niraparib and dostarlimab were administered concurrently for 18 weeks, and 50.0% in arm B (n = 24), where patients received 3 weeks of lead-in niraparib before the combination was administered for 15 weeks. In the total patient population, RBC-1, RBC-II, and RBC-III rates were 8.7%, 10.9%, and 4.3%, respectively. RCB status was incalculable in 2.2% of patients. Notably, 23.9% of patients received additional neoadjuvant therapy. Overall, the RCB-0 and RCB-I response rate was 60.0%.
“Additional, ongoing correlative work may help fully understand the impact of combining immunologic approaches with PARP inhibition in BRCA carriers with TNBC,” lead study author Erica L. Mayer, MD, MPH, said in a presentation of the data.
Mayer is an institute physician and director of Breast Cancer Clinical Research at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School, in Boston, Massachusetts.
Although evidence has not supported the use of immune checkpoint inhibition in combination with PARP inhibition in the advanced setting for patients with TNBC harboring BRCA mutations, investigators hypothesized that this strategy could have a larger impact in the early-stage setting, where immunosuppression is reduced.
Investigators enrolled patients at least 18 years of age with histologically or cytologically confirmed invasive, stage I to III breast cancer with a primary tumor size at least 1.0 cm.2 All patients needed to have HER2-negative disease and germline BRCA1/2 or PALB2 mutations.1 In arms A and B, patients were required to have TNBC.2
Patients with TNBC were randomly assigned to receive niraparib plus dostarlimab for 18 weeks in arm A, or lead-in niraparib monotherapy for 3 weeks, followed by niraparib plus dostarlimab for 15 weeks, in arm B.1 Arm C included patients with estrogen receptor–positive, HER2-negative disease; this group received the combination for 18 weeks. In all groups, niraparib was dosed at 200 mg once per day, and dostarlimab was given at 500 mg once every 3 weeks.
The trial’s primary end points were pCR rate and change in stromal tumor-infiltrating lymphocytes (sTILs) from baseline to cycle 2.
In the total population of arms A and B, patients had a median age of 39.3 years (range, 24.8-72.8), and most were White (84.8%). Tumor stages comprised I (37.0%), II (45.7%), and III (17.4%). Most patients (76.1%) had node-negative disease and grade 3 tumors (87.0%). Additionally, 82.6% of patients harbored BRCA1 mutations, and 17.4% had BRCA2 mutations.
The mean number of dostarlimab cycles received was 5.1, and 82.6% of patients completed the target number of cycles. Niraparib was given for a mean of 5.7 cycles, and 82.6% of patients completed 6 cycles.
Among evaluable patients in arm A (n = 15), sTILs increased from a mean of 16% at baseline to 27.4% at 3 weeks (P = .009). In arm B (n = 22), they increased from 19.5% at baseline to 42.1% at 3 weeks (P = .0003).
Patients who achieved a pCR had higher baseline sTILs (median, 15%) compared with those without a pCR (median, 5%; P = .03). Additionally, those who experienced RCB-0/I had a median sTILs level of 15% at baseline vs 5% for those without RCB-0/I (P = .04).
Notably, changes in sTILs level from baseline to cycle 2 (odds ratio [OR], 0.69; 95% CI, 0.15-3.14), baseline PD-L1 expression (OR, 1.96; 95% CI, 0.52-7.41), and baseline estrogen receptor expression (OR, 1.0; 95% CI, 0.13-7.78) were not associated with pCR.
Regarding safety, grade 2 or higher treatment-related adverse effects (TRAEs) occurred in 82.6% of patients, including 54.3% at grade 2, 26.1% at grade 3, and 2.2% at grade 4. The most common grade 2 or higher TRAEs reported in at least 10% of patients included anemia (26.1%), fatigue (21.7%), hypertension (15.2%), hypothyroidism (15.2%), neutropenia (15.2%), rash (13.0%), and headache (10.9%).
Treatment was discontinued in 13% of patients due to either toxicity and inadequate response or progression (6.5% each). Dostarlimab only was discontinued in 5 patients, and 7 patients discontinued only niraparib.
Disclosures: Mayer reported serving as a consultant for AstraZeneca, Novartis, Lilly, Genentech, and Aktis.
Related Content:
