Kimberly L. Blackwell, MD Discusses Trastuzumab's Efficacy in HER2-Positive Breast Cancer

In stage I breast cancer, adjuvant trastuzumab and paclitaxel were investigated in HER2-positive patients with small tumors measuring up to 3 cm. Historically, these patients would not receive trastuzumab; however, after a median follow-up of 4 years, the 3-year invasive disease-free survival rate was 98.7% (95% CI, 97.6-99.8) in patients who received trastuzumab and paclitaxel.¹

The ongoing AFFINITY trial, which is examining chemotherapy and trastuzumab with or without pertuzumab (Perjeta) in the adjuvant setting, may have a big impact on adjuvant treatment for HER2-positive breast cancer once the data are released, says Blackwell.

Blackwell, the director of the Breast Cancer Program at Duke Cancer Institute, says the information from the study regarding trastuzumab has shaped her practice.

"This data has shaped my practice. In patients who have very small HER2-driven tumors, before, I wouldn’t have recommended trastuzumab across the board, but now based on that study, I am. This is practice-changing," she said.

"However, there are no data that giving trastuzumab without chemotherapy works. When you make the decision that you are going to recommend or offer trastuzumab in small tumors, the downside is that it’s always administered with chemotherapy. That made it a harder decision historically because all the stage I HER2-positive breast cancers were excluded from the previous studies and we really had no data to draw on for decision making."

Blackwell adds that she feels as though the stage is currently set in breast cancer to possibly move away from chemotherapy and into the realm of using more trastuzumab-backed therapies, which would avoid chemotherapy toxicities.

The ongoing AFFINITY trial, which is examining chemotherapy and trastuzumab with or without pertuzumab (Perjeta) in the adjuvant setting, may have a big impact on adjuvant treatment for HER2-positive breast cancer once the data are released, says Blackwell.

There are also several studies investigating the antibody-drug conjugate ado-trastuzumab emtansine (T-DM1; Kadcyla). These include the ADAPT study, which demonstrated a pathological complete response (pCR) rate of 40.5% with T-DM1 as neoadjuvant treatment in patients with HER2-positive and HR-positive early breast cancer.²

"I think the biggest advance in the past year or 2 is a better understanding of the poor prognosis for a woman with stage I breast cancer that is HER2-positive who does not receive adjuvant trastuzumab," said Blackwell. "We tend to think of very small TIb and TIa tumors as very low risk for recurrence. However, we now have several retrospective studies looking at risk of recurrence in patients who do not get trastuzumab and who have small tumors."

Turning toward pertuzumab, Blackwell says the drug has its place in treating women with stage II breast cancer that is HER-2driver, as well as stage III breast cancer.

"The data now suggest that pertuzumab added to chemotherapy plus trastuzumab backbone, adds something, at least in the neoadjuvant setting. I think the approval of pertuzumab in the neoadjuvant setting has really set a standard of care for stage II and III breast cancer. The preferred regimen is now to incorporate pertuzumab to what you were going to give anyway, chemotherapy and trastuzumab," she said.

"The data suggest that there is not a lot of added toxicity, but you get a near doubling in the complete pathologic response rate. For me, adding pertuzumab in the neoadjuvant setting is a fairly easy recommendation based on its approval in this setting."

References

1. Tolaney SM, Barry WT, Dang CT. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med. 2015;372(2):134-141.
2. Harbeck N, Gluz O, Christgen M, et al. Efficacy of 12-weeks of neoadjuvant TDM1 with or without endocrine therapy in HER2-positive hormone-receptor-positive early breast cancer: WSG-ADAPT HER2+/HR+ phase II trial. J Clin Oncol. 2015;33 (suppl; abstr 506).