Evanthia Roussos Torres, MD, PhD, discusses the phase 1 study of the efficacy of entinostat administered in combination with nivolumab and ipilimumab for the treatment of locally advanced, metastatic, unresectable, or HER2-negative breast cancer.
Evanthia Roussos Torres, MD, PhD, assistant professor of medicine at the University of Southern California Keck School of Medicine, discusses the phase 1 study [NCT02453620] of the efficacy observed with entinostat (MS-275) administered in combination with nivolumab (Opdivo) and ipilimumab (Yervoy) for the treatment of locally advanced, metastatic, unresectable, or HER2-negative breast cancer.
Entinostat is a histone deacetylase inhibitor that is being investigated for its role in reducing tumor cell growth by blocking required enzymes. According to Roussos Torres, it has been studied previously as a monotherapy in blood cancers.
The phase 1 trial of 24 patients with advanced breast cancer investigated the safety and optimal dosage for entinostat and nivolumab when given with ipilimumab to patients with locally advanced, metastatic, or HER2-negative breast cancer. To determine the proper dosage, 6 patients received an escalating dose. Eighteen patients received the highest dose with acceptable toxicity, which was oral entinostat given at 5 mg weekly with a 2-week run-in before receiving nivolumab 3mg/kg twice per week and ipilimumab 1 mg/kg twice weekly.
The primary end point was assessing safety of the triplet combination. Patients with grade 3 and 4 adverse events (AEs) included 17% (n = 4) with anemia, 13% (N=3) who experienced a decreased neutrophil count, and 8% (n = 2) with increased lipase. The most common immune-related AEs included rash (n = 7, 29%), hypothyroidism (n = 5, 21%), and pneumonitis (n = 2, 8%). The objective response rate by RECIST (v1.1) was 30% (6/20 evaluable), including 1 complete response.
Based on the safety dosage identified and the 30% ORR, the investigators recommended further trials of the triplet combination.
TRANSCRIPTION:
0:08 | The ORR was 30%, with response observed in both HER2-positive and triple-negative subtypes. The majority of these responses occurred in patients with triple-negative breast cancer [TNBC]. There was 1 patient who showed a complete response at the 6-month time point. The duration of response ranged from less than 2 months to the longest response ongoing at greater than 24 months after initiation of treatment. The median progression-free survival for the overall cohort was short, at 2.5 months, and the median overall survival [OS] was 7.7 months in all patients, 24.4 months in patients with TNBC, and 5.9 months in patients with hormone receptor-positive disease.
Of note, those driving improved OS are the patients who experienced [a] response. We're also going to discuss correlative studies that investigated immunohistochemical staining of T cells, which demonstrates that the ratio of CD8+ T effector cells over FOXP3 T regulatory cells increased after therapy from baseline to time point 1, which was the baseline compared to the entinostat run-in and then to time point 2 after combination therapy. This is primarily as a result of the increase in CD8+ T cells’ infiltration, and this is most notable in biopsies from patients with TNBC.
Managing HER2+ Early Breast Cancer: Insights and Future Horizons
November 28th 2023Sandra M. Swain, MD, FACP, FASCO, discusses the potential role for HER2-directed TKIs for the treatment of patients with early-stage HER2+ breast cancer and shares insights about emerging data that could impact the future treatment landscape.
Read More
Navigating HER2+ Early Breast Cancer: Insights Into the Current Treatment Landscape
November 28th 2023In this companion article, Sandra M. Swain, MD, FACP, FASCO, provides insights into effective management of patients with early-stage HER2+ breast cancer and reviews recent data in the evolving treatment landscape.
Read More
Breast Cancer Leans into the Decade of Antibody-Drug Conjugates, Experts Discuss
September 25th 2020In season 1, episode 3 of Targeted Talks, the importance of precision medicine in breast cancer, and how that vitally differs in community oncology compared with academic settings, is the topic of discussion.
Listen
FDA Oks FoundationOne®CDx for Capivasertib/Fulvestrant in Breast Cancer
November 22nd 2023In addition to the approval of capivasertib and fulvestrant, the FDA has granted approval to the FoundationOne® CDx as a companion diagnostic to identify patients with advanced HR-positive, HER2-negative advanced breast cancer.
Read More