Elacestrant plus alpelisib in an ESR1 and PIK3CA co-mutated and heavily pretreated metastatic breast cancer: the first case report for combination efficacy and safety

Breast cancer (BC) is the leading cause of cancer-related mortality among women, and hormone receptor (HR)-positive subtype makes up the majority of all cases. The standard of care in HR + /HER2 − metastatic BC (MBC) is endocrine therapy (ET) plus a CDK4/6 inhibitor (CDK4/6i). ESR1 mutations could impair the clinical efficacy of the ETs. Similarly, PIK3CA mutations may serve as a negative prognostic marker. Furthermore, MBC is challenging to treat despite new drug approvals. Our patient received multiple lines of ET ± CDK4/6i and chemotherapy but persistently progressed after each or stopped the treatment due to adverse events. Here we showed for the first time that an all-oral combination of elacestrant plus alpelisib was feasible, tolerable, and clinically active in an ESR1 and PIK3CA co-mutated and heavily pretreated patient. We achieved a remarkable response in the metastatic lesions with minor toxicity issues. This case highlights the importance of utilizing up-to-date therapeutic agents and reactive decision-making during personalized cancer treatment.