The recent approval of novel HER2-targeted therapies has improved options for the treatment of patients with HER2-positive metastatic breast cancer (mBC), particularly those with brain metastases. More data are needed on optimal sequencing of therapy and therapies for subgroups of patients with HER2-positive disease, according to experts who participated in a recent virtual Around the Practice panel. The panel was moderated by V.K. Gadi, MD, PhD, the University of Illinois Cancer Center in Chicago, Illinois, and included Neil Iyengar, MD, Memorial Sloan Kettering Cancer Center in New York, New York; Claudine Isaacs, MD, Georgetown University in Washington, DC; and Virginia Kaklamani, MD, University of Texas Health San Antonio in San Antonio.
The objectives of the interactive panel, which included a live audience, were to discuss current treatment approaches and challenges for patients with relapsed or refractory HER2-positive mBC as well as new data from clinical studies presented at the 2021 American Society of Clinical Oncology (ASCO) Annual meeting. The panel reviewed case studies of patients with HER2-positive mBC and discussed factors to consider for third-line therapies, such as quality of life (QOL).
CURRENT TREATMENT APPROACHES AND CHALLENGES
As noted by Iyengar, the increased use of neoadjuvant therapy for early-stage disease has changed the treatment landscape for HER2-positive mBC. He typically uses the HER2/neu receptor antagonists trastuzumab (Herceptin) and pertuzumab (Perjecta) with a taxane to maximize volume reduction in the neoadjuvant setting, followed by dual HER2-targeted therapy with trastuzumab and pertuzumab in the adjuvant setting. (1,2) Results from the APHINITY trial (NCT01358877) showed that the 3-year rate of invasive disease-free survival (DFS) was higher with pertuzumab than with placebo when added to chemotherapy and trastuzumab in patients with node-positive or high-risk node-negative HER2-positive operable breast cancer (94.1% vs 93.2%; HR, 0.81; 95% CI, 0.66-1.00; P=.045). (3)
In addition, Iyengar said he considers trastuzumab emtansine (Kadcyla; T-DM1) for patients with a substantial amount of residual disease in the adjuvant setting, based on results from the phase 3 KATHERINE trial (NCT01772472), which showed 3-year invasive DFS was higher with T-DM1 (88.3%) than with trastuzumab (77%) in patients with residual invasive disease in the breast or axilla after receiving neoadjuvant therapy with trastuzumab and a taxane. (4)Poll Question 1. Which of the studies listed below is most relevant to you? (a) Postneoadjuvant studies 8% Pertuzumab, trastuzumab, nab-paclitaxel 8% Neoadjuvant studies 25% DESTINY-Breast01 HER2CLIMB 25% 34% (a) N = 12 Poll Question 2. Are the data from ASCO 2021 and the discussion you heard today likely to change your practice? (a) No 45% Yes 55% ASCO, American Society of Clinical Oncology. (a) N = 11
Also, Iyengar typically uses a taxane with trastuzumab and pertuzumab in the first-line metastatic setting. This is based on end-of-study results from the phase 3 CLEOPATRA trial (NCT00567190), which showed that the group treated with pertuzumab, trastuzumab, and docetaxel had a longer median overall survival (OS) than the group treated with placebo, trastuzumab, and docetaxel (57.1 vs 40.8 months; HR, 0.69; 95% CI, 0.58-0.82; P<.0001). (5)
According to Iyengar,...