Adjuvant Carboplatin and PARP Inhibitor Combination Trials in TNBC

Rebecca Shatsky, MD UC San Diego School of Medicine | Rahul Gosain, MD, MBA Wilmot Cancer Institute | Rohit Gosain, MD Roswell Park Comprehensive Cancer Center

Key Points

• Adjuvant carboplatin showed positive survival benefits when added to adjuvant primary chemotherapy in patients with triple-negative breast cancer (TNBC) in the RJBC 1501 and CITRINE trials.

• Adjuvant carboplatin may be more appropriate for younger patients or older patients with known chemotherapy–sensitizing characteristics, such as high Ki-67 or germline BRCA mutations.

• Neoadjuvant PARP inhibitor and immunotherapy combinations achieved high pathologic complete response (pCR) rates in phase 2 TNBC trials.

TNBC Presentations From SABCS 2025

Cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Goasin, MD, of Roswell Park Comprehensive Cancer Center, met with Rebecca Shatsky, MD, of UC San Diego School of Medicine, to discuss TNBC data presented at the 2025 San Antonio Breast Cancer Symposium (SABCS 2025). The doctors reviewed data on adjuvant carboplatin from the RJBC 1501 and CITRINE trials, and data on PARP inhibitors plus immunotherapy from the TBCRC-056 and OlympiaN trials. 

Adjuvant Carboplatin Improves DFS in RJBC 1501 

RJBC 1501 was a prospective phase 3 trial evaluating adjuvant epirubicin plus cyclophosphamide (EC) followed by a taxane (T), or EC followed by T and carboplatin in patients with early-stage TNBC. The addition of carboplatin was associated with improved disease-free survival (DFS; HR, 0.66; 95% CI, 0.44-0.97; P = .034). The 3-year DFS rate was 89.8% (95% CI, 86.8-92.9) with EC and T versus 93.1% (95% CI, 90.5-95.7) with EC and T plus carboplatin. Carboplatin was also associated with improved distant DFS (HR, 0.61; 95% CI, 0.38-0.98; P = .04) and overall survival (OS; HR, 0.39; 95% CI, 0.16-0.94; P = .029).

This study joins other recent trials in investigating whether the addition of carboplatin in the adjuvant setting provides more than just higher pCR rates and actually improves survival outcomes. Although the absolute DFS difference between arms was small, the DFS rates overall were very positive, and the data as a whole suggest that carboplatin is important in curative-intent therapy for TNBC, said Dr. Shatsky.

CITRINE: Intensifying Chemotherapy With Carboplatin in TNBC

The phase 3 CITRINE trial evaluated dose-dense epirubicin and cyclophosphamide followed by weekly paclitaxel with or without carboplatin as adjuvant therapy in high-risk, early-stage TNBC. High-risk disease was defined as either regional node–positive or node–negative with Ki-67 of 50% or greater. The addition of carboplatin to adjuvant chemotherapy significantly improved 3-year rates of DFS (HR, 0.64; 95% CI, 0.43-0.95; P = .026), recurrence-free survival (HR, 0.59; 95% CI, 0.37-0.93; P = .021), distant DFS (HR, 0.61; 95% CI, 0.37-0.98; P = .039), and OS (HR, 0.41; 95% CI, 0.20-0.83; P = .011).

The inclusion criteria of node–positive or node–negative with high Ki-67 were an important factor because they functionally excluded patients with luminal androgen receptor TNBC subtype, which is less sensitive to chemotherapy, said Dr. Shatsky. Similar to RJBC 1501, the positive data support the value of adjuvant carboplatin in the treatment of TNBC. Broadly, Shatsky said she would select adjuvant carboplatin in younger patients or older patients who have higher Ki-67 or a known BRCA mutation.

Neoadjuvant Niraparib Plus Dostarlimab in TNBC

In the phase 2 TBCRC-056 trial, neoadjuvant niraparib plus dostarlimab was assessed in patients with stage I, II, or III TNBC with germline BRCA or PALB2 mutations. The SABCS 2025 presentation covered patients who received either doublet niraparib and dostarlimab for 6 cycles (arm A) or niraparib monotherapy for 1 cycle followed by niraparib plus dostarlimab for 5 cycles (arm B). After 6 cycles, patients underwent surgery or received additional neoadjuvant treatment.

The pCR rate at the time of surgery was 50% for both arms. In addition, 26.1% of patients had residual disease, and 23.9% crossed over to additional neoadjuvant therapy. Common grade 2 or higher side effects included anemia (26.1%), fatigue (21.7%) hypertension (15.2%), hypothyroidism (15.2%), neutropenia (15.2%), rash (13%), and headache (10.9%). Overall, the study showed a “very exciting” pCR rate for a non-chemotherapy regimen in TNBC, said Dr. Shatsky. 

OlympiaN: Neoadjuvant Olaparib With or Without Durvaluamb in TNBC

The phase 2 OlympiaN trial evaluated neoadjuvant olaparib with or without durvalumab in patients with stage I or stage II estrogen receptor (ER)–negative or ER–low, HER2–negative, early-stage breast cancer with germline BRCA mutations. Patients with stage T1bN0 or T1cN0 disease (cohort A) received olaparib monotherapy, while patients with T2N0 or T1N1 disease received olaparib plus durvalumab, both followed by surgery. Cohort A had a pCR rate of 68% (95% CI, 47-85) and a combined residual cancer burden (RCB) 0 or RCB 1 rate of 72% (95% CI, 51-88). Cohort B had a pCR rate of 80% (95% CI, 59-93) and a combined RCB 0 or RCB 1 rate of 84% (95% CI, 64-95). 

While the OlympiaN population was slightly lower risk compared with the TBCRC-056 population, the pCR rates achieved were extremely favorable. The RBC 0 or RCB 1 rate with olaparib monotherapy in cohort A was particularly exciting, as checkpoint inhibitors can introduce long-term toxicities, said Dr. Shatsky.

In practice, based on available safety data, Dr. Shatsky said she would be comfortable adding olaparib to patients on adjuvant pembrolizumab per the KEYNOTE-522 regimen, although only in patients who did not achieve a pCR with neoadjuvant therapy and definitive surgery.