Adding Entinostat to ICI Dual Therapy Delivers Promising Responses in TNBC

Publication
Article
Targeted Therapies in OncologyApril I, 2024
Volume 13
Issue 5
Pages: 76

Although immune checkpoint inhibitors have become a cornerstone of therapy across cancer settings, their use in most breast cancer settings has fallen short.

Findings from a breast cancer expansion cohort of the phase 1 trial, ETCTN-9844 (NCT02453620), evaluating entinostat, nivolumab (Opdivo), and ipilimumab (Yervoy), demonstrated an objective response rate (ORR) of 25% (95% CI, 8.7%-49.1%) and clinical benefit rate (CBR) of 40% in heavily pretreated patients with HER2-negative breast cancer.1 Although immune checkpoint inhibitors (ICIs) have become a cornerstone of therapy across cancer settings, their use in most breast cancer settings has fallen short. Adding entinostat, the class I histone deacetylases inhibitor, to dual therapy has shown promise in preclinical studies.

“We don’t see reliable responses from immune checkpoint inhibition [in breast cancer] the way we see it in a large percentage of patients with certain lung cancers or melanoma,” lead author Evanthia T. Roussos Torres, MD, PhD, assistant professor of medicine, Keck School of Medicine of USC, Los Angeles, California, said during an interview with Targeted Therapies in Oncology.

What further distinguishes this study is that it doesn’t involve chemotherapy, Roussos Torres said. “This regimen could lead to treatment options for patients who are ineligible for chemotherapy, either because of chemotherapy-related toxicities or lack of response,” she said.

Patients were pooled from the dose expansion cohorts from ETCTN-9844, which followed a modified 3 + 3 dose escalation design with 4 dose levels (DLs; FIGURE).2

Patients in DL 1/2 received 3 to 5 mg of entinostat weekly plus 3 mg/kg of nivolumab every 2 weeks. At DL 3/4, patients received 3 to 5 mg entinostat weekly plus nivolumab and 1 mg/kg of ipilimumab every 6 weeks.2

A total of 24 women with metastatic breast cancer were enrolled in the dose expansion study; 12 with hormone receptor–positive (HR+) and 12 with triple-negative breast cancer (TNBC). The primary end point was to further confirm the safety of the triplet therapy and the secondary end point was the assessment of preliminary tumor activity per RECIST 1.1 and immune-related RECIST.1

Patients were a median age of 55 years (range, 38-77) and the majority (71%) were White. Patients were treated with a median number of 6.5 prior regimens and patients with HR-positive disease, in particular, had a median number of 8 prior treatments. Patients who had TNBC had a median of 4 prior regimens.1

Twenty of the 24 enrolled patients had evaluable disease for response. Among the 5 responders, 1 patient had a complete response (TNBC) and 4 had a partial response (3 with TNBC and 1 with HR- positive disease). For patients with HR-positive breast cancer, the ORR was 10% (95% CI, 0.3%-44.5%).1

The investigators noted that the study demonstrates that the addition of entinostat to dual ICI therapy is a safe and promising strategy for metastatic breast cancer.

They cautioned that further investigation is needed to determine if entinostat provides a clinical benefit compared with dual ICIs alone.

Overall, Roussos Torres said that trials such as this “provide an opportunity to change the clinical trial space so that the findings in a trial run parallel to findings in the laboratory. As a result, we’re able to apply the science to get the most out of clinical trials—information about clinical outcomes and scientific mechanisms driving these outcomes. It’s tremendous that the field is moving in this direction because it will allow us to translate the findings into practice much faster and get the most out of the generous participation from our patients."

REFERENCES:
1. Roussos Torres ET, Ho WJ, Danilova L, et al. Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial. Nat Cancer. Published online February 14, 2024. doi:10.1038/s43018-024-00729-w
2. Roussos Torres ET, Rafie C, Wang C, et al. Phase I study of entinostat and nivolumab with or without ipilimumab in advanced solid tumors (ETCTN-9844). Clin Cancer Res. 2021;27(21):5828-5837. doi:10.1158/1078-0432.CCR-20-5017
Related Videos
Video 5 - "Second-Line Treatment Considerations and Improving Outcomes in Breast Cancer"
Video 4 - "Impressions on Safety Data from EMERALD Subgroup Analysis"
Video 3 - "EMERALD: Elacestrant for ER+/HER2- Advanced Breast Cancer"
Related Content