ADC for residual disease after KEYNOTE-522
Patients whose TNBC survives chemo-immunotherapy before surgery have a high relapse risk. Give them an ADC after surgery.
The KATHERINE model (T-DM1 for HER2+ residual disease) applied to TNBC with TROP2 ADCs. Several trials (ASCENT-05/OptimICE-RD with sacituzumab + pembrolizumab, TROPION-Breast03 with Dato-DXd) are testing this.
For stage II-III triple-negative breast cancer, chemotherapy plus pembrolizumab before surgery and pembrolizumab alone afterwards is now the standard approach worldwide, and the survival gain is real, not just a surrogate. It does not apply to stage I disease or to hormone-receptor-positive or HER2-positive cancers. The price is a year of immunotherapy with a meaningful chance of a permanent endocrine side effect such as hypothyroidism or adrenal insufficiency.
Sacituzumab govitecan is a standard second-line or later treatment for metastatic triple-negative breast cancer, roughly doubling survival compared with the chemotherapies it was tested against. Patients should expect neutropenia and diarrhoea, which are manageable with growth factor support and loperamide. Trials are now testing it earlier, in first-line combinations with pembrolizumab and after surgery for residual disease.
HER2-positive breast cancer is now routinely treated before surgery so that the pathology result can guide what comes after: patients with no residual cancer continue trastuzumab (with or without pertuzumab), while those with residual disease switch to T-DM1. This model of using the tumour's response as a test has since been copied in triple-negative and other cancers.