Maintenance Pembrolizumab Therapy in Patients with Metastatic HER2-negative Breast Cancer with Prior Response to Chemotherapy

Authors

Toshiaki Iwase
Evan N Cohen
Hui Gao
Angela Alexander
Megumi Kai
Vivian Chiv
Xiaoping Wang
Savitri Krishnamurthy
Diane Liu
Yu Shen
Kumiko Kida
Alexandre Reuben
Rachel M Layman
David L Ramirez
Debasish Tripathy
Stacy L Moulder
Clinton Yam
Vicente Valero
Bora Lim
James M Reuben
Naoto T Ueno

Publication Date

6-3-2024

Journal

Clinical Cancer Research

DOI

10.1158/1078-0432.CCR-23-2947

PMID

38629963

PMCID

PMC11147689

PubMedCentral® Posted Date

12-3-2024

PubMedCentral® Full Text Version

Author MSS

Abstract

Purpose: 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 and methods: Patients with a complete response, partial response, or stable disease (SD) after at least three 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, and response biomarkers in the blood.

Results: Of 43 treated patients, 11 had metastatic IBC and 32 non-IBC TNBC. The 4-month DCR was 58.1% [95% confidence interval (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 with those who did not achieve SD (20% vs. 5.9% mean increase, respectively; P = 0.04).

Conclusions: Pembrolizumab monotherapy achieved durable treatment responses. Patients with a high baseline T-cell clonality had prolonged disease control with pembrolizumab.

Keywords

Humans, Female, Antibodies, Monoclonal, Humanized, Middle Aged, Receptor, ErbB-2, Aged, Adult, Antineoplastic Agents, Immunological, Biomarkers, Tumor, Triple Negative Breast Neoplasms, Neoplasm Metastasis, Breast Neoplasms, Maintenance Chemotherapy

Published Open-Access

yes

Recommended Citation

Iwase, Toshiaki; Cohen, Evan N; Gao, Hui; et al., "Maintenance Pembrolizumab Therapy in Patients with Metastatic HER2-negative Breast Cancer with Prior Response to Chemotherapy" (2024). Faculty, Staff and Student Publications. 3516.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/3516