Oncotarget

Research Papers:

Durvalumab and tremelimumab before surgery in patients with hormone receptor positive, HER2-negative stage II–III breast cancer

Haven R. Garber _, Sreyashi Basu, Sonali Jindal, Zhong He, Khoi Chu, Akshara Singareeka Raghavendra, Clinton Yam, Lumarie Santiago, Beatriz E. Adrada, Padmanee Sharma, Elizabeth A. Mittendorf and Jennifer K. Litton

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Oncotarget. 2024; 15:238-247. https://doi.org/10.18632/oncotarget.28567

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Abstract

Haven R. Garber1, Sreyashi Basu2, Sonali Jindal2, Zhong He2, Khoi Chu2, Akshara Singareeka Raghavendra1, Clinton Yam1, Lumarie Santiago3, Beatriz E. Adrada3, Padmanee Sharma4, Elizabeth A. Mittendorf5,6,7 and Jennifer K. Litton1

1 Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

2 Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

3 Department of Breast Imaging, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

4 Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

5 Department of Surgery, Division of Breast Surgery, Brigham and Women’s Hospital, Boston, MA 02115, USA

6 Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston MA 02115, USA

7 Harvard Medical School, Boston, MA 02115, USA

Correspondence to:

Haven R. Garber, email: [email protected]

Keywords: breast cancer; ER positive; immunotherapy; neoadjuvant chemotherapy; tumor microenvironment

Received: February 05, 2024     Accepted: February 22, 2024     Published: March 19, 2024

Copyright: © 2024 Garber et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

A clinical trial was conducted to assess the feasibility of enrolling patients with Stage II or III hormone receptor positive (HR+)/HER2-negative breast cancer to pre-operative dual PD-L1/CTLA-4 checkpoint inhibition administered prior to neoadjuvant chemotherapy (NACT). Eight eligible patients were treated with upfront durvalumab and tremelimumab for two cycles. Patients then received NACT prior to breast surgery. Seven patients had baseline and interval breast ultrasounds after combination immunotherapy and the responses were mixed: 3/7 patients experienced a ≥30% decrease in tumor volume, 3/7 a ≥30% increase, and 1 patient had stable disease. At the time of breast surgery, 1/8 patients had a pathologic complete response (pCR). The trial was stopped early after 3 of 8 patients experienced immunotherapy-related toxicity or suspected disease progression that prompted discontinuation or a delay in the administration of NACT. Two patients experienced grade 3 immune-related adverse events (1 with colitis, 1 with endocrinopathy). Analysis of the tumor microenvironment after combination immunotherapy did not show a significant change in immune cell subsets from baseline. There was limited benefit for dual checkpoint blockade administered prior to NACT in our study of 8 patients with HR+/HER2-negative breast cancer.


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