Dr. Tripathy on Personalized Therapy Options in Metastatic Breast Cancer

Debu Tripathy, MD, professor and chairman, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses personalized therapy options in metastatic breast cancer.

PARP inhibitors olaparib (Lynparza) and talazoparib (Talzenna) were approved in 2018 for the treatment of patients with germline BRCA-mutated HER2-negative metastatic breast cancer, based on improved progression-free survival demonstrated with the agents in the phase III OlympiAD and EMBRACA trials, respectively.

Patients with DNA damage repair defects who may have enhanced immunogenic tumors appear to be more susceptible to PARP inhibitors, says Tripathy. Since an overall survival benefit has not yet been shown, PARP inhibitors in combination with immunotherapy are being explored in clinical trials.

CDK4/6 inhibitors have also demonstrated unprecedented first- and second-line survival benefits for patients with metastatic hormone receptor (HR)—positive disease, says Tripathy. Further understanding addressable resistance mechanisms is critical to solidifying these agents as initial or second-line treatment.

Finally, the PI3K inhibitor alpelisib (Piqray) in combination with fulvestrant (Faslodex) was granted FDA approval for the treatment of patients with HR-positive, HER2-negative metastatic breast cancer whose tumors harbor a PIK3CA mutation. Additional studies are needed to determine other targets within the PI3K-Akt pathway, concludes Tripathy.

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