Individualizing Early-Stage HER2-Positive Breast Cancer

It’s important to individualize therapy for early-stage HER2-positive breast cancer as more agents become approved, Sara A. Hurvitz, MD said in a presentation at the 37th Annual Miami Breast Cancer Conference, held from March 5-8, 2020 in Miami, Florida.

There are currently 4 approved agents for early stage HER2-positive breast cancer, including trastuzumab (Kanjinti) and pertuzumab (Perjeta) in the neoadjuvant and adjuvant settings, neratinib (Nerlynx) as an extended adjuvant therapy, and the newly approved T-DM1 (Kadcyla) in the adjuvant setting for patients who have residual disease after surgery. 

Particularly, Hurvitz suggested that the addition of trastuzumab has altered the natural history of early-stage HER2-positive breast cancer, making its prognosis as good as that of disease that does not overexpress HER2. However, she also indicated that even with this option available, patients are still at risk of recurrence.

“We can no longer tell patients if you make it to 5 years [without recurrence] with this type of breast cancer you’re out of the woods. There is a risk long-term of it coming back,” Hurvitz said. “And so, we do need new therapies to try and help improve the odds of cure for our patients.”

Currently, neratinib and pertuzumab are available for use with curative intent. Pertuzumab is approved by the FDA in combination with trastuzumab and chemotherapy as an adjuvant treatment for patients with HER2-positive early stage breast cancer at high risk of recurrence. Neratinib is approved for extended treatment of patients with HER2-positive early-stage breast cancer after standard adjuvant trastuzumab. Both neratinib and pertuzumab have sparked significant improvements in disease-free survival, with a relative risk reduction of approximately 17% to 19%, Hurvitz said. Both are also associated with an increase in toxicity. 

It is not clear how some of these therapies will work sequentially, Hurvitz said. She pointed out that neratinib was not studied in patients who received prior neoadjuvant or adjuvant pertuzumab, or in patients who received adjuvant T-DM1. Furthermore, pertuzumab in the adjuvant setting was not studied in patients who were treated with that drug or another as neoadjuvant therapy, and pertuzumab in the adjuvant setting was not studied in patients who went on to receive neratinib. 

Using the CONTROL, APHINITY, KATHERINE, and ATEMPT studies, which each looked at a combination of the approved therapies in early-stage HER2-positive breast cancer, Hurvitz assessed the risk factors and outcomes of each trial to detail a proposed strategy for patients with HER2-positive stage I-III breast cancer. 

For patients with cT1a/b cN0 HER2-positive breast cancer, she recommended surgery followed by trastuzumab-based therapy (adjuvant paclitaxel [Abraxane] and trastuzumab [APT] or T-DM1, though T-DM1 is not yet approved in this setting). However, for patients in this setting found to be high-risk (<35, grade 3 ER/PR-negative, multifocal), she suggested neoadjuvant TCH (docetaxel [Taxotere], carboplatin [Paraplatin], and trastuzumab), TCHP (docetaxel, carboplatin, trastuzumab, and pertuzumab) or FEC/TH(P) (fluorouracil [Fluoroplex], epirubicin [Ellence], cyclophosphamide [Cytoxan], docetaxel, and trastuzumab) or AC-THP (doxorubicin [Adriamycin], cyclophosphamide, paclitaxel, trastuzumab, and pertuzumab). 

For those with ≥cT1c or ≥cN1 HER2-positive breast cancer, Hurvitz also proposed TCH, TCHP, FEC/TH(P), or AC-TH(P). Should the patient have residual invasive disease, she recommended they be treated with 14 cycles of T-DM1, or neratinib if the patient is hormone response (HR)-positive and lymph node-positive. If no residual disease is present, she suggested the use of trastuzumab once a year or a combination of trastuzumab and pertuzumab once a year if they began with LN+ disease. 

“Now we are in an era where we are considering de-escalation approaches for these small tumors,” Hurvitz explained. 

Hurvitz noted that these recommendations are not set in stone, and further research should support the treatment suggestions. 

Reference:

Hurvitz SA. Individualizing Therapy for Early-Stage HER2+ Breast Cancer. Presented at the 37th Annual Miami Breast Cancer Conference, held from March 5-8, 2020.