Efficacy and safety of camrelizumab combined with apatinib in advanced triple-negative breast cancer: an open-label phase II trial
Open accessAbstract
Background: Previous trials showed that antiangiogenesis or anti-programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) monotherapy only showed marginal effect in triple-negative breast cancer (TNBC). Preclinical studies demonstrated that antiangiogenic therapy could sensitize breast cancer to PD-1/PD-L1 blockade via reprogramming tumor microenvironment. Combinational treatment of checkpoint blockade and antiangiogenesis for TNBC has not been reported. Methods: Patients with advanced TNBC with less than three lines of systemic therapy were enrolled in an open-label, non-comparative, two-arm, phase II trial at Sun Yat-sen Memorial Hospital. Camrelizumab (intravenously every 2 weeks) with apatinib orally at either continuous dosing (d1–d14) or intermittent dosing (d1–d7) was given until disease progression or unacceptable toxicities. Primary endpoint was objective response rate (ORR). Results: From January 2018 to April 2019, 40 patients were enrolled, including 10 in the apatinib intermittent dosing cohort and 30 in the apatinib continuous dosing cohort. The ORR was 43.3% (13 of 30) in the continuous dosing cohort, while no objective response was observed in the intermittent dosing cohort. The disease control rate was 63.3% (19 of 30) in the apatinib continuous dosing cohort, and 40.0% (4 of 10) in the apatinib intermittent dosing cohort, respectively. The median progression-free survival (PFS) was 3.7 (95% CI 2.0 to 6.4) months and 1.9 (95% CI 1.8 to 3.7) months in the continuous dosing and intermittent dosing cohort, respectively. In the continuous dosing cohort, the median PFS of patients with partial response (8.3 months, 95% CI 5.9 to not reached) was significantly longer than that of patients with stable disease/progressive disease/not evaluable (2.0 months, 95% CI 1.7 to 3.0). The most common adverse events (AEs) included elevated aspartate aminotransferase/alanine aminotransferase and hand-foot syndrome. Overall, 26.7% and 20.0% of patients experienced grade ≥3 AEs in the continuous dosing and intermittent dosing cohort, respectively. In the continuous dosing cohort, a high percentage of baseline tumor-infiltrating lymphocytes (>10%) was associated with higher ORR and favorable PFS (p=0.029, 0.054, respectively). Conclusions: The ORR by this chemo-free regimen was dramatically higher than previously reported ORR by anti-PD-1/PD-L1 antibody or apatinib monotherapy. Camrelizumab combined with apatinib demonstrated favorable therapeutic effects and a manageable safety profile in patients with advanced TNBC. Trial registration number: NCT03394287 .
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Combination therapies such as sintilimab plus anlotinib, sintilimab plus IBI305, camrelizumab plus apatinib, and toripalimab plus axitinib demonstrated potent antitumor effects in multiple types of cancers.
“Combination therapies such as sintilimab plus anlotinib, sintilimab plus IBI305 (bevacizumab biosimilar), camrelizumab plus apatinib, and toripalimab plus axitinib demonstrated potent antitumor effects in multiple types of cancers [22, 114–120].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [115]
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Combination strategies with PD-1/PD-L1 blockade: current advances and future directions
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- Authors
- Liu, J., Liu, Q., Li, Y., Li, Q., Su, F., Yao, H., Su, S., Wang, Q., Jin, L., Wang, Y., Lau, W. Y., Jiang, Z., & Song, E.
- Affiliations
- Sun Yat-sen University (CN)
- Jiangsu Hengrui Medicine (China) (CN)
- Chinese University of Hong Kong (HK)
- Chinese PLA General Hospital (CN)
- Corresponding author
- Liu, Qiang
- Li, Qian
- Jiang, Zefei
- Song, Erwei
- ORCID
- Venue
- Journal for ImmunoTherapy of Cancer
- Publisher
- BMJ
- Published
- 2020-05
- Volume
- 8
- Issue
- 1
- Pages
- e000696
- ISSN
- 2051-1426 (ISSN-L)
- PMC
- PMC7252975
- OpenAlex
- W3027448020
- Cited by
- 183
- References
- 30
- Citations by year
- 2026: 20 · 2025: 30 · 2024: 35 · 2023: 40 · 2022: 34 · 2021: 21 · 2020: 3
- FWCI
- 8.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal for ImmunoTherapy of Cancer (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Sun Yat-sen Memorial Hospital (Clinical Research Program (SYS-Q-201701))
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Keywords
- camrelizumab, apatinib, triple-negative breast cancer, PD-1/PD-L1 blockade, anti-angiogenic therapy, combination immunotherapy, tumor microenvironment reprogramming, intermittent dosing, continuous dosing, objective response rate, progression-free survival, treatment safety, hand-foot syndrome, hepatotoxicity, advanced breast cancer, first-line therapy, second-line therapy, third-line therapy
- MeSH terms
- Progression-Free Survival, Immune Checkpoint Inhibitors, Administration, Oral, Adult, Antineoplastic Combined Chemotherapy Protocols, Drug Administration Schedule, Drug Synergism, Female, Humans, Middle Aged, Pyridines, Angiogenesis Inhibitors, Tumor Microenvironment, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized, Administration, Intravenous, Triple Negative Breast Neoplasms, Response Evaluation Criteria in Solid Tumors
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