PMID- 32448804 OWN - NLM STAT- MEDLINE DCOM- 20210607 LR - 20210607 IS - 2051-1426 (Electronic) IS - 2051-1426 (Linking) VI - 8 IP - 1 DP - 2020 May TI - Efficacy and safety of camrelizumab combined with apatinib in advanced triple-negative breast cancer: an open-label phase II trial. LID - 10.1136/jitc-2020-000696 [doi] LID - e000696 AB - 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. CI - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Liu, Jieqiong AU - Liu J AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Liu, Qiang AU - Liu Q AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China songew@mail.sysu.edu.cn victorlq@hotmail.com jiangzefei@csco.org.cn. FAU - Li, Ying AU - Li Y AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Li, Qian AU - Li Q AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Su, Fengxi AU - Su F AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Yao, Herui AU - Yao H AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Su, Shicheng AU - Su S AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Wang, Quanren AU - Wang Q AD - Jiangsu Hengrui Medicine Co., Ltd, Jiangsu, China. FAU - Jin, Liang AU - Jin L AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Wang, Ying AU - Wang Y AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Lau, Wan Yee AU - Lau WY AD - Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hongkong, China. FAU - Jiang, Zefei AU - Jiang Z AD - Department of Oncology, The Fifth Medical Centre of Chinese PLA General Hospital, Beijing, China songew@mail.sysu.edu.cn victorlq@hotmail.com jiangzefei@csco.org.cn. FAU - Song, Erwei AU - Song E AUID- ORCID: 0000-0002-5400-9049 AD - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China songew@mail.sysu.edu.cn victorlq@hotmail.com jiangzefei@csco.org.cn. AD - Fountain-Valley Institue for Life Sciences, 4th Floor, Building D, Guangzhou Institue of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. LA - eng SI - ClinicalTrials.gov/NCT03394287 PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Immunother Cancer JT - Journal for immunotherapy of cancer JID - 101620585 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Immune Checkpoint Inhibitors) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 0 (Pyridines) RN - 5S371K6132 (apatinib) RN - 73096E137E (camrelizumab) SB - IM MH - Administration, Intravenous MH - Administration, Oral MH - Adult MH - Angiogenesis Inhibitors/administration & dosage/adverse effects MH - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects MH - Drug Administration Schedule MH - Drug Synergism MH - Female MH - Humans MH - Immune Checkpoint Inhibitors/administration & dosage/adverse effects MH - Middle Aged MH - Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology MH - Progression-Free Survival MH - Pyridines/*administration & dosage/adverse effects MH - Response Evaluation Criteria in Solid Tumors MH - Triple Negative Breast Neoplasms/*drug therapy/immunology/mortality MH - Tumor Microenvironment/drug effects/immunology PMC - PMC7252975 OTO - NOTNLM OT - breast neoplasms OT - clinical trials, phase II as topic OT - immunotherapy OT - programmed cell death 1 receptor COIS- Competing interests: None declared. EDAT- 2020/05/26 06:00 MHDA- 2021/06/08 06:00 PMCR- 2020/05/24 CRDT- 2020/05/26 06:00 PHST- 2020/04/17 00:00 [accepted] PHST- 2020/05/26 06:00 [entrez] PHST- 2020/05/26 06:00 [pubmed] PHST- 2021/06/08 06:00 [medline] PHST- 2020/05/24 00:00 [pmc-release] AID - jitc-2020-000696 [pii] AID - 10.1136/jitc-2020-000696 [doi] PST - ppublish SO - J Immunother Cancer. 2020 May;8(1):e000696. doi: 10.1136/jitc-2020-000696.