Maintenance pembrolizumab therapy in patients with metastatic HER2-negative breast cancer with prior response to chemotherapy

• Published in: Clinical cancer research Vol. 30; no. 11; pp. OF1 - OF9
• Main Authors: Iwase, Toshiaki, Cohen, Evan N, Gao, Hui, Alexander, Angela, Kai, Megumi, Chiv, Vivian, Wang, Xiaoping, Krishnamurthy, Savitri, Liu, Diane, Shen, Yu, Kida, Kumiko, Reuben, Alexandre, Layman, Rachel, Ramirez, David, Tripathy, Debu, Moulder, Stacy L, Yam, Clinton, Valero, Vicente, Lim, Bora, Reuben, James M, Ueno, Naoto T
• Format: Journal Article
• Language: English
• Published: United States 03.06.2024
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-23-2947

Accumulating toxicities hinder indefinite chemotherapy for many patients with metastatic/recurrent HER2-negative breast cancer. We conducted a phase II trial of pembrolizumab monotherapy following induction chemotherapy to determine the efficacy of maintenance immunotherapy in patients with metastatic HER2-negative inflammatory breast cancer (IBC) and non-IBC triple-negative breast cancer (TNBC) and a biomarker study. Patients with a complete response (CR), partial response (PR), or stable disease (SD) after at least 3 cycles of chemotherapy for HER2-negative breast cancer received pembrolizumab, regardless of programmed death-ligand 1 expression. Pembrolizumab (200 mg) was administered every 3 weeks until disease progression, intolerable toxicity, or 2 years of pembrolizumab exposure. The endpoints included the 4-month disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and response biomarkers in the blood. Of 43 treated patients, 11 had metastatic IBC and 32 non-IBC TNBC. The 4-month DCR was 58.1% (95% CI, 43.4%-72.9%). For all patients, the median PFS was 4.8 months (95% CI, 3.0-7.1 months). The toxicity profile was similar to the previous pembrolizumab monotherapy study. Patients with high T-cell clonality at baseline had a longer PFS with pembrolizumab treatment than did those with low T-cell clonality (10.4 vs. 3.6 months, p = 0.04). Patients who achieved SD also demonstrated a significant increase in T-cell clonality during therapy compared to those who didn't achieve SD (20% vs. 5.9% mean increase, respectively; p = 0.04). Pembrolizumab monotherapy achieved durable treatment responses. Patients with a high baseline T-cell clonality had prolonged disease control with pembrolizumab.