Dr Mahtani on Treatment Sequencing in HER2+ Metastatic Breast Cancer

Reshma Lillaney Mahtani, DO, chief, Breast Medical Oncology, Baptist Health Wellness and Medical Complex, discusses available therapies in the first-, second-, and later-line settings in patients with HER2-positive metastatic breast cancer.

HER2-targeted treatment decisions in the first and second lines are often based on standard algorithms that guide the care of patients with HER2-positive breast cancer, Mahtani says. One standard frontline treatment option is pertuzumab (Perjeta) plus trastuzumab (Herceptin) and taxane-based chemotherapy. Final overall survival (OS) results from the phase 3 CLEOPATRA trial (NCT00567190) showed that patients who received the pertuzumab combination achieved a median overall survival (OS) of 56.5 months vs 40.8 months in those who received placebo, trastuzumab, and docetaxel.

In the second-line setting, findings from the phase 3 DESTINY-Breast03 trial (NCT03529110), a head-to-head study comparing the antibody-drug conjugates fam-trastuzumab deruxtecan-nxki (Enhertu) and ado-trastuzumab emtansine (Kadcyla), establishedtrastuzumab deruxtecan as the standard of care for most patients with HER2-positive metastatic breast cancer. In DESTINY-Breast03, the median progression-free survival (PFS) was 28.8 months with trastuzumab deruxtecan vs 6.8 months with trastuzumab emtansine. Another option in the second line and beyond, especially for patients with significant central nervous system metastases, is tucatinib (Tukysa) plus capecitabine (Xeloda) and trastuzumab, based on findings from the phase 2 HER2CLIMB trial (NCT02614794), Mahtani notes. In HER2CLIMB, the 1-year PFS rate was 33.1% in patients who received the tucatinib combination vs 12.3% in those who received placebo plus trastuzumab and capecitabine.

In the third-line setting and beyond, treatment recommendations should be individualized based on factors such as patient preference for oral vs intravenous therapies, disease burden, symptomatology, and the adverse effect profiles of the treatments, Mahtani explains. Although treatment decisions in the later-line settings are not as clearly defined as those in the earlier-line settings, several treatment regimens are available, Mahtani says. For instance, margetuximab-cmkb (Margenza) plus chemotherapy, approved by the FDA in 2020 based on findings from the phase 3 SOPHIA trial (NCT02492711), is a potential option for some patients. Trastuzumab emtansine, neratinib in combination with capecitabine, and chemotherapy in combination with trastuzumab could also be considered, Mahtani concludes.