HCQ+ADC vs ADC in the Treatment of Advanced Breast Cancer

Breast cancer is the most prevalent malignant tumor in the world, and 30% of breast cancer patients will enter the advanced stage due to treatment failure. Most patients with advanced breast cancer have had distant organ metastasis, and the median progression free survival period is only 1-2 years. In the past, advanced breast cancer patients faced the dilemma of poor survival due to the lack of precise targeted therapy. However, through a series of clinical studies, experts in the field of advanced breast cancer have successfully expanded the indications of ADC-based combination targeted therapy from the emergence of first generation ADC to the third generation ADC with "bystander effect", which has significantly prolonged the survival time of patients. Trastuzumab Deruxtecan (T-DXd) and Sacituzumab Govitecan (SG) are new ADC drugs targeting HER2 or TROP-2 with high efficacy and low toxicity after the progress of first-line treatment. Because both ADC and autophagy involve lysosomes, and the relationship between ADC and autophagy microenvironment has not been elucidated, the combination of autophagy regulators and ADC may be a treatment option that can benefit some patients more.The autophagy agents hydroxychloroquine or chloroquine has become the only FDA (Food and Drug Administration) approved autophagy inhibitor. And the synergistic effect of hydroxychloroquine and antibody-drug conjugate (ADC) has already been confirmed based on preliminary experiments of our research group. We envisage that Trastuzumab Deruxtecan (T-DXd) or Sacituzumab Govitecan (SG) combined with hydroxychloroquine(HCQ) in the treatment of advanced breast cancer in clinical practice has the advantages of improving efficacy and survival. Therefore, we intend to further validate the efficacy and safety of the Autophagy inhibitor hydroxychloroquine(HCQ) in combination with the latest ADC drugs (T-DXd or SG) in a Phase I/II, randomized, controlled clinical study, in order to provide advanced breast cancer patients with a better choice of precision targeted therapy.