Dual Targeting Promising for HER2+/HR+ Breast Cancer
The discovery of crosstalk between HER2 and hormone receptor (HR) pathways led to the promising treatment strategy of dual targeting regimens, according to a presentation at the 2018 Miami Breast Cancer Conference (March 8-11, 2018).
William J Gradishar, MD, Northwestern University Feinberg School of Medicine, displayed key trials showing the efficacy of dual targeted therapy in HER2+/HR+ breast cancer.
The phase III ALTERNATIVE trial included a total of 355 women with HER2+/HR+ breast cancer who were randomized them to three groups—lapatinib plus trastuzumab and an aromatase inhibitor (AI), trastuzumab plus an AI, or lapatinib plus an AI.
Results of this study showed the median PFS was 11 months for women assigned to lapatinib/trastuzumab plus an AI compared with 5.7 months for patients assigned to trastuzumab plus an AI. The median PFS was 8.3 months for lapatinib/AI.
The phase II PERTAIN trial enrolled 258 postmenopausal women with HER2+/HR+ locally advanced or metastatic breast cancer. Patients were randomly assigned to receive pertuzumab with trastuzumab (n= 129) or trastuzumab alone (n = 129) in combination with an AI.
Researchers reported the median PFS was 18.89 months with the pertuzumab triplet compared with 15.80 months for trastuzumab and an AI alone. In patients with measurable disease, the ORR with the pertuzumab combination was 63.3% compared with 55.7% for trastuzumab and an AI alone.
Additionally, researchers noted the complete response (CR) rate with the pertuzumab triplet was 7.3%, and 56% of patients had a partial response (PR). In the trastuzumab/AI arm, the CR rate was 0.9% and the PR rate was 54.7%. At the analysis, 26.6% and 27.4% of patients had stable disease (SD), with and without pertuzumab, respectively. The disease control rate (CR + PR + SD) was 89.9% with pertuzumab compared with 83% without.
The median duration of response was 27.10 months with the pertuzumab triplet compared with 15.11 months for trastuzumab and an AI alone.
The results from these two studies supported the hypothesis that dual targeting enhances progression-free survival and increases the response rate. Dual targeting leads to a promising treatment strategy using for HER2+/HR+ breast cancer, Dr Gradishar concluded.—Janelle Bradley
