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Clinical Trial
. 2024 Jun 3;30(11):2424-2432.
doi: 10.1158/1078-0432.CCR-23-2947.

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

Toshiaki Iwase  1   2   3 , Evan N Cohen  2   4 , Hui Gao  2   4 , Angela Alexander  2 , Megumi Kai  2 , Vivian Chiv  2 , Xiaoping Wang  1   2   3 , Savitri Krishnamurthy  2   5 , Diane Liu  6 , Yu Shen  6 , Kumiko Kida  7 , Alexandre Reuben  8 , Rachel M Layman  1   2 , David L Ramirez  1 , Debasish Tripathy  1 , Stacy L Moulder  9 , Clinton Yam  1 , Vicente Valero  1   2 , Bora Lim  1   2   10 , James M Reuben  2   4 , Naoto T Ueno  1   2   3
Affiliations
Clinical Trial

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

Toshiaki Iwase et al. Clin Cancer Res. .

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.

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Conflict of interest statement

Rachel Layman has consulting or advisory roles for Eli Lilly, Novartis Celcuity Biotheryx, and Gilead Sciences, receives research funding from Accutar Biotechnology, Eli Lilly, Novartis, Pfizer, Puma, Zentalis, Celcuity, and Arvinas.

Debu Tripathy has consulting or advisory roles for Novartis, Pfizer, GlaxoSmithKline, Genomic Health, AstraZeneca, OncoPep, Sermonix, Personalis, Ambrx, Roche, and Gilead Sciences; receives research funding from Polyphor, Pfizer, and Ambrx; and receives travel and accommodation expenses from Novartis and AstraZeneca.

Stacy L Moulder is an employee of Eli Lilly.

Bora Lim has consultancy or advisory roles for Celcuity, Natera, Daichi-Sankyo, Novartis, Pfizer, and AstraZeneca; received honoraria from Puma Biotechnology, Novartis, and Pfizer; and receives grant/research funding from Genentech, Takeda, Merck, Celcuity, Eli Lilly, Puma Biotechnology, Calithera Therapeutics, NCI, DOD, CPRIT, Hope Foundation, and Adopt-a-Scientist.

Naoto T Ueno has consulting or advisory roles for AstraZeneca, Bayer AG, Pfizer, Gilead Sciences, Chugai Pharmaceutical, CytoDyn, Daiichi Sankyo, DynaMed, Eisai, KeChow Pharma, Lavender Health, OBI Pharma, OncoCyte, Ourotech, DBA Pear Bio, Kirilys Therapeutics, Peptilogics, Phoenix Molecular Designs, Preferred Medicine, Puma Biotechnology, Sumitomo Dainippon Pharma, Sysmex, Takeda Pharmaceuticals, Unitech Medical, CARNA Biosciences, ChemDiv, DualityBio, LARVOL, Oncolys BioPharma, Rakuten Medical, Merck, AnHeart Therapeutics, Carisma Therapeutics, Lilly, and Therimunex; has speaker or preceptorship roles for Bristol-Myers Squibb, CareNet, Chugai Pharmaceutical, Genomic Health, Kyowa Hakko Kirin, Sumitomo Dainippon Pharma, and Medscape; and receives research funding from AnHeart Therapeutics, Eisai, Gilead Sciences, Phoenix Molecular Designs, Daiichi Sankyo, Puma Biotechnology, Merck, Oncolys BioPharma, OBI Pharma, ChemDiv, Tolero Pharmaceuticals, and VITRAC Therapeutics.

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, David Ramirez, Vicente Valero, and James M Reuben have no conflicts of interest.

Figures

Figure 1.
Figure 1.
Progression-free survival duration stratified by the response to prior chemotherapy. Abbreviations: CR, complete response; PR, partial response; SD, stable disease.
Figure 2.
Figure 2.
Progression-free survival by baseline T-cell clonality. Abbreviation: BL, baseline.
Figure 3.
Figure 3.
Changes in peripheral blood T-cell activation in response to 2 courses of pembrolizumab maintenance therapy. Responders had larger increases in their peripheral blood T-cell activation than did non-responders. Abbreviation: PFS, progression-free survival.
See this image and copyright information in PMC

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