Mo et al. reported the safety and efficacy of metronomic chemotherapy with PD-1 blockade in metastatic HER2-negative breast cancer. Ninety-seven patients were randomized to receive metronomic vinorelbine (NVB) monotherapy, or anti-PD-1 plus NVB alone, with bevacizumab, with conventional cisplatin, or with metronomic cyclophosphamide and capecitabine (VEX cohort). All treatments were well tolerated. The disease control rate was highest in the VEX (69.7%) and cisplatin (73.7%) cohorts. The VEX cohort achieved the highest ORR, longest median PFS (6.6 months), and duration of disease control (up to 7.9 months). Metronomic VEX chemotherapy reprogrammed the systemic immune response toward immunotherapy efficacy.
Contributed by Shishir Pant
ABSTRACT: It remains unclear whether metronomic chemotherapy is superior to conventional chemotherapy when combined with immune checkpoint blockade. Here we performed a phase 2 clinical trial of metronomic chemotherapy combined with PD-1 blockade to compare the efficacy of combined conventional chemotherapy and PD-1 blockade using Bayesian adaptive randomization and efficacy monitoring. Eligible patients had metastatic HER2-negative breast cancer and had not received more than one prior line of standard chemotherapy. Patients (total n_=_97) were randomized to receive (1) metronomic vinorelbine (NVB) monotherapy (n_=_11), (2) NVB plus anti-PD-1 toripalimab (n_=_7), (3) anti-angiogenic bevacizumab, NVB and toripalimab (n_=_27), (4) conventional cisplatin, NVB and toripalimab (n_=_26), or (5) metronomic cyclophosphamide, capecitabine, NVB and toripalimab (the VEX cohort) (n_=_26). The primary endpoint was disease control rate (DCR). Secondary objectives included progression-free survival (PFS) and safety. The study met the primary endpoint. The VEX (69.7%) and cisplatin (73.7%) cohorts had the highest DCR. The median PFS of patients in the VEX cohort was the longest, reaching 6.6_months, followed by the bevacizumab (4.0_months) and cisplatin (3.5_months) cohorts. In general, the five regimens were well tolerated, with nausea and neutropenia being the most common adverse events. An exploratory mass cytometry analysis indicated that metronomic VEX chemotherapy reprograms the systemic immune response. Together, the clinical and translational data of this study indicate that metronomic VEX chemotherapy combined with PD-1 blockade can be a treatment option in patients with breast cancer. ClinicalTrials.gov Identifier: NCT04389073 .
Author Info: (1) Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medica
Author Info: (1) Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. (2) Department of Biostatistics, Peking University Clinical Research Institute, Beijing, China. (3) Department of Medical Oncology, Cancer Hospital of HuanXing ChaoYang District, Beijing, China. (4) Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. (5) Department of Biostatistics, Peking University Clinical Research Institute, Beijing, China. (6) Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. (7) Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. (8) Department of Medical Oncology, Cancer Hospital of HuanXing ChaoYang District, Beijing, China. (9) Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. (10) Department of Medical Oncology, Cancer Hospital of HuanXing ChaoYang District, Beijing, China. (11) Department of Biostatistics, Peking University Clinical Research Institute, Beijing, China. (12) State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. qianhaili@pumc.edu.cn. (13) Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. xubinghe@csco.org.cn. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. xubinghe@csco.org.cn. (14) Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. drmafei@126.com. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. drmafei@126.com.
