Clinical activity of nivolumab in combination with eribulin in HER2-negative metastatic breast cancer: A phase IB/II study (KCSG BR18-16)

Se Hyun Kim; Seock-Ah Im; Koung Jin Suh; Kyung-Hun Lee; Min Hwan Kim; Joohyuk Sohn; Yeon Hee Park; Ji-Yeon Kim; Jae Ho Jeong; Kyoung Eun Lee; In Sil Choi; Kyong Hwa Park; Hee-Jun Kim; Eun Kyung Cho; So Yeon Park; Milim Kim; Jee Hyun Kim

doi:10.1016/j.ejca.2023.113386

Clinical activity of nivolumab in combination with eribulin in HER2-negative metastatic breast cancer: A phase IB/II study (KCSG BR18-16)

Eur J Cancer. 2023 Dec:195:113386. doi: 10.1016/j.ejca.2023.113386. Epub 2023 Oct 14.

Authors

Se Hyun Kim¹, Seock-Ah Im², Koung Jin Suh¹, Kyung-Hun Lee², Min Hwan Kim³, Joohyuk Sohn³, Yeon Hee Park⁴, Ji-Yeon Kim⁴, Jae Ho Jeong⁵, Kyoung Eun Lee⁶, In Sil Choi⁷, Kyong Hwa Park⁸, Hee-Jun Kim⁹, Eun Kyung Cho¹⁰, So Yeon Park¹¹, Milim Kim¹², Jee Hyun Kim¹³

Affiliations

¹ Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
² Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University, College of Medicine, Seoul, South Korea.
³ Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
⁴ Hematology-Oncology, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁵ Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁶ Department of Hematology and Oncology, Ewha Womans University Hospital, Seoul, South Korea.
⁷ Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, South Korea.
⁸ Division of Medical Oncology/Hematology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, South Korea.
⁹ Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, South Korea.
¹⁰ Division of Medical Oncology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea.
¹¹ Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
¹² Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea; Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
¹³ Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea. Electronic address: jhkimmd@snu.ac.kr.

PMID: 37890351
DOI: 10.1016/j.ejca.2023.113386

Abstract

Aim: We evaluated the efficacy and safety of nivolumab and eribulin combination therapy for metastatic breast cancer (BC) in Asian populations.

Methods: In this parallel phase II study, adult patients with histologically confirmed recurrent/metastatic hormone receptor-positive/HER2-negative (HR+HER2-) or triple-negative BC (TNBC) were prospectively enroled from 10 academic hospitals in Korea (ClinicalTrials.gov Identifier: NCT04061863). They received nivolumab (360 mg) on day 1 plus eribulin (1.4 mg/m²) on days 1 and 8 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was the investigator-assessed 6-month progression-free survival (PFS) rate in each subtype. Secondary endpoints included investigator-assessed objective response rate (ORR) as per Response Evaluation Criteria in Advanced Solid Tumors version 1.1, disease control rate, overall survival, and treatment toxicity. The association between PD-L1 expression and efficacy was investigated.

Results: Forty-five patients with HR+HER2- BC and 45 with TNBC were enroled. Their median age was 51 (range, 31-71) years, and 74 (82.2%) received one or two prior treatments before enrolment. Six-month PFS was 47.2% and 25.1% in the HR+HER2- and TNBC cohorts, respectively. Median PFS was 5.6 (95% confidence interval [CI]: 5.3-7.4) and 3.0 (95% CI: 2.1-5.2) months in the HR+HER2- and TNBC groups, respectively. ORRs were 53.3% (complete response [CR]: 0, partial response [PR]: 24) and 28.9% (CR: 1, PR: 12). Patients with PD-L1+ tumours (PD-L1 expression ≥1%) and PD-L1- tumours (ORR 50% versus 53.8% in HR+HER2-, 30.8% versus 29.0% in TNBC) had similar ORRs. Neutropenia was the most common grade 3/4 adverse event; the most common immune-related adverse events (AEs) were grades 1/2 hypothyroidism and pruritus. Five patients discontinued therapy because of immune-related AEs.

Conclusion: Nivolumab plus eribulin showed promising efficacy and tolerable safety in previously treated HER2- metastatic BC.

Trial registration: NCT04061863.

Keywords: Advanced breast cancer; Clinical trial; Eribulin; Immune checkpoint inhibitors; Luminal breast cancer; Metastatic breast cancer; Nivolumab.

Publication types

Clinical Trial, Phase II
Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols / adverse effects
B7-H1 Antigen
Breast Neoplasms* / pathology
Female
Humans
Middle Aged
Nivolumab / therapeutic use
Receptor, ErbB-2 / metabolism
Triple Negative Breast Neoplasms* / drug therapy

Substances

B7-H1 Antigen
eribulin
Nivolumab
Receptor, ErbB-2

Associated data

ClinicalTrials.gov/NCT04061863