Sacituzumab Govitecan in Primary HER2-negative Breast Cancer - NCT04595565

Neoadjuvant chemotherapy (NACT) allows monitoring of tumor response to treatment and a pathological complete response (pCR) is associated with superior survival. This association is strongest in the most aggressive subtype, i.e. in patients with triple-negative breast cancer (TNBC). Patients with TNBC not achieving a pCR have a 5-year event free survival rate of about 50%. , , The association between pCR and prognosis is less pronounced in HR-positive/HER2-negative patients. However, the CPS+EG scoring system for prognosis after neoadjuvant chemotherapy, taking into account clinical stage, post treatment pathological stage, estrogen receptor status and grade, leads to an improved estimate of prognosis allowing to select patients at high risk of relapse for post-neoadjuvant therapy. Patients with TNBC not achieving a pCR as well as those with HR-positive/HER2-negative tumors and a CPS+EG score of 3 or 2/ypN+ are at high risk of relapse, warranting additional experimental therapies after NACT.

There is proof of concept, that post-neoadjuvant therapy can significantly improve survival. First data was provided by the CREATE X trial, randomizing patients with residual tumor after neoadjuvant chemotherapy to either capecitabine or observation. CREATE X included HER2-negative patients and demonstrated a significant improvement in disease-free survival (DFS) and overall survival (OS) in the overall population, which was confined to the TNBC subgroup.

Recently, the randomized post-neoadjuvant phase III KATHERINE study demonstrated an improved invasive disease-free survival in HER2-positive patients without pCR after trastuzumab +/- pertuzumab treated postoperatively with T-DM1, an antibody-drug-conjugate compared to trastuzumab.