Retrospective Results Show High pCR With Dose-Dense Regimen in HER2+ Breast Cancer

Jasmeet C. Singh, MD

Neoadjuvant dose-dense doxorubicin and cyclophosphamide plus paclitaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta; ACTHP) led to encouraging pathologic complete response (pCR) rates in patients with HER2-positive breast cancer, according to results of a retrospective analysis.

In the single-institution study, investigators analyzed medical records from patients with HER2-positive breast cancer who were treated with dose-dense ACTHP in the neoadjuvant setting followed by adjuvant anti-HER2 therapy, from September 1, 2013, to March 1, 2016. All patients had HER2-positive disease, defined by immunohistochemistry 3+ and/or fluorescence in situ hybridization of >2.0.

Of the 235 evaluable patients, 62% achieved a pCR. Moreover, at a median follow-up of 3.8 years, the 3-year invasive disease-free survival (iDFS) rate was 91% (95% CI, 88%-95%) for all evaluable patients, 94% (95% CI, 90%-98%) for patients who achieved a pCR, and 87% (95% CI, 80%-95%) for patients who did not achieve a pCR (P = .051).

Additional results showed that the 3-year overall survival rate was 96% (95% CI, 94%-99%) in all patients, 98% (95% CI, 95%-100%) for those who had a pCR, and 93% (95%, CI 88-99%) for patients who did not have a pCR (P = .12).

“The iDFS rates with dose-dense ACTHP were quite high, at about 90%. It confirms that patients who achieve a pCR have better outcomes compared with patients who don't have a pCR in HER2-positive disease,” said lead study author Jasmeet C. Singh, MD.

In an interview with OncLive, Singh, a medical oncologist at Memorial Sloan Kettering Cancer Center, discussed the findings of a retrospective analysis and how they may impact treatment for patients with HER2-positive breast cancer.

OncLive: Could you provide an overview of this retrospective analysis and the findings?

Singh: We have previously demonstrated that dose-dense ACTHP, with dose-dense doxorubicin and cyclophosphamide administered every 2 weeks, followed by weekly paclitaxel, along with trastuzumab and pertuzumab administered every 3 weeks, leads to high pCR rates when administered [in the neoadjuvant setting] in HER2-positive breast cancer.

In this particular study, we looked at iDFS rates of patients treated at our institution with the dose-dense ACTHP regimen. There were 235 patients overall who receive preoperative dose-dense ACTHP; 95% of those patients continued postoperative trastuzumab/pertuzumab. The iDFS rates were 91% in all patients. In patients who did not have a pCR, the iDFS rate was 87%, while it was 94% for patients who achieved a pCR. The patients who had a pCR did very well overall.

What impact could these data have on the HER2-positive cancer paradigm?

The impact is really two-fold. First of all, because we are having such excellent clinical responses, especially tremendous downstaging of disease in the axilla, we are able to perform less-aggressive surgeries. We can avoid axillary lymph node dissection in our patients, which is really amazing in terms of avoiding morbidity. Second of all, we have shown that these are not just numerical improvements. These really translate into better DFS outcomes. It is pretty exciting.

What is the safety profile of this regimen?

Thus far, these regimens have been very well tolerated. The biggest concern with using an anthracycline in combination with trastuzumab/pertuzumab or anti-HER2 agents is really cardiotoxicity. There are other studies, such as the BERENICE trial, which is a cardiac safety study of anthracyclines in combination with trastuzumab/pertuzumab. Basically, the grade 3/4 cardiac adverse event rate is low, at about 1.5%. We haven't seen a lot of cardiotoxicity with these regimens. These treatments have been well tolerated.

What are the next steps of this trial?

We have already come a long way in our HER2-positive populations, but there is always room for improvement. There might be some interest in looking at novel combinations of these dual HER2-targeted therapies with immunotherapy to further improve pCR rates and overall response. We have some exciting pCR data in triple-negative disease, which shows that immunotherapy really adds to improvement in pCR rates. In a totally different scenario, it may be useful to see if we can avoid surgery in patients who have excellent responses. This is a question of the future.

Singh JC, Patil S, Norton L, et al. Disease free survival rate with dose dense doxorubicin and cyclophosphamide followed by weekly paclitaxel with trastuzumab and pertuzumab (ddACTHP) in patients with HER2-positive early stage breast cancer: a single institution experience. Presented at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract P2-16-10.