Neoadjuvant tislelizumab plus nab-paclitaxel and carboplatin followed by adjuvant tislelizumab in patients with early triple-negative breast cancer.

602 Background: Triple-negative breast cancer (TNBC) is the subtype with the least favorable outcomes. However, TNBC is associated with higher immune cell abundance than other subtypes, making it a good candidate for immunotherapy. Neoadjuvant chemotherapy is the preferred treatment approach for early TNBC. Emerging evidence shows that additional immune checkpoint inhibitors (ICI) in neoadjuvant therapy significantly increases pathological complete response (pCR) and event-free survival in early TNBC. Treatment regimens of paclitaxel and carboplatin (TP) is class I recommendation for TNBC neoadjuvant therapy, the application of ICI with TP regimens is worth exploring. Methods: In this multicenter, open-label, phase II study, patients with untreated, histologically confirmed TNBC in stage II-III (per AJCC 8th edition) were enrolled. Patients received six cycles of neoadjuvant therapy with tislelizumab at 200 mg once every 3 weeks plus nab-paclitaxel (125 mg/m2 on days 1 and 8) and carboplatin (at a dose based on an area under the concentration 2 on days 1 and 8) every 3 weeks. Patients who either completed or discontinued the neoadjuvant treatment would undergo definitive surgery. After surgery, the patients received adjuvant tislelizumab every 3 weeks for up to 12 cycles. The primary endpoint was the rate of pCR (ypT0/Tis ypN0). The secondary endpoints included 1-, 2-, 3-year event free survival rates and overall survival rates. Based on the Simon’s Two-Stage design, if > 13 of 32 patients achieved pCR, the enrollment would proceed to full accrual of 62 patients as planned. If > 29 of 62 patients achieved pCR, we would deem the study to have met the primary endpoint. Results: From Mar 2021 to Jan 2022, 32 patients were enrolled; 18 of them achieved pCR, and therefore the study proceeded to complete the enrollment of 62 patients. At the data cut-off of Oct 13, 2022, 62 patients were enrolled, among which 50 patients received neoadjuvant treatment and underwent definitive surgery. The median age was 50 years. 36 (72.0%) patients had stage II breast cancer at diagnosis. 31 of the 50 patients achieved pCR (ypT0/Tis ypN0), and the pCR rate was 62.0% (95% CI, 47.2-75.4). Patients with immune cell PD-L1 expression ≥10% had numerically higher pCR rate (81.8% vs 53.6%) than those with PD-L1 expression ≥1%. All 50 (100%) patients reported any grade of neoadjuvant treatment-related adverse events (TRAEs). Grade ≥3 TRAEs occurred in 27 (54%) patients. The rate of immune-related adverse events (irAEs) was 34% (17/50), with the common occurring (10%) irAE of hypothyroidism (n = 8, 16%). 2 (4.9%) patients experienced grade ≥3 irAEs. Severe adverse events were reported in 5 (10%) patients. Conclusions: The study has met its primary endpoint. Tislelizumab plus nab-paclitaxel and carboplatin achieved a higher pCR and was generally well tolerated in the neoadjuvant treatment of early TNBC. Clinical trial information: ChiCTR2100041675 .