Dr McArthur on the Optimal Sequencing of Treatments in Metastatic TNBC

Heather Lynn McArthur, MD, MPH, associate professor, Department of Internal Medicine, member, Hematology and Oncology Division, UT Southwestern Medical Center, clinical director, Breast Cancer Program, Simmons Cancer Center, discusses key factors considered in the optimal sequencing of first- and second-line treatment options in patients with advanced triple-negative breast cancer (TNBC).

Before determining a treatment approach in the first-line setting, a biopsy of the metastatic tissue should be performed to confirm the diagnosis. Additional testing for PD-L1 status may be performed on either the biopsied tissue or primary breast tissue to predict the patient’s potential clinical benefit from pembrolizumab (Keytruda) plus chemotherapy. This combination was approved by the FDA on November 3, 2020, for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors are PD-L1 positive (combined positive score ≥10).

Patients with TNBC whose tumors are PD-L1 negative will instead be treated with a taxane or platinum-based chemotherapy depending on their disease-free interval from the initiation of curative intent therapy and whether they have de novo metastatic disease.

Germline mutational status further affects treatment selection, as patients with BRCA1/2 mutations may experience benefit from the PARP inhibitors olaparib (Lynparza) and talozoparib (Talzenna), or platinum chemotherapy. 

Both PARP inhibitors and platinum chemotherapy may also be considered for patients with BRCA1/2 mutations in the second line. For patients with high tumor mutational burden or microsatellite instability, the immune checkpoint inhibitor pembrolizumab should be utilized. Lastly, fam-trastuzumab deruxtecan-nxki (Enhertu) and single-agent chemotherapy could also be considered for this population.

These same options are viable for use in the third-line setting and beyond. Additionally, the novel antibody-drug conjugate sacituzumab govitecan-hziy (Trodelvy) received approval on April 7, 2021, for patients with unresectable locally advanced or metastatic TNBC who had progressed on 2 or more systemic therapies. Ultimately, a patient’s treatment approach in this setting is dependent on what agents they received in prior lines of therapy.