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 .
ABSTRACT
The current state of oncology medical services is not encouraging and is unable to fully meet the needs of patients with cancer. In recent years, rapidly developing artificial intelligence technology and gradual advancements in mobile phones, sensors, and wearable devices, which have made these more compact, affordable, and popular, have greatly expanded the development of digital medicine. Digital medicine refers to clinical evidence-based technology and products with a direct impact on disease management and research. Integrating digital medicine into clinical practice has the advantages of broader applicability, greater cost-effectiveness, better accessibility, and improved diagnostic and therapeutic performance. Digital medicine has emerged in different clinical application scenarios, including cancer prevention, screening, diagnosis, and treatment, as well as clinical trials. Additionally, big data generated from digital medicine can be used to improve levels of clinical diagnosis and treatment. However, digital medicine also faces many challenges, including security regulation and privacy protection, product usability, data management, and optimization of algorithms. In summary, the application and development of digital medicine in the field of cancer face numerous opportunities and challenges.
