Harold J. Burstein, MD, PhD, senior physician, associate professor of medicine, Harvard Medical School, Dana-Farber Cancer Institute, discusses the treatment landscape of HER2-positive breast cancer.

Early-stage HER2-positive breast cancers have a very good prognosis, explains Burstein. Physicians tend to use anti-HER2 drugs in combination with chemotherapy to prevent disease recurrence. Women who have higher-risk disease are generally managed with chemotherapy alongside trastuzumab (Herceptin) and pertuzumab (Perjeta). That was informed by the results of the APHINITY trial, in which patients were randomized to trastuzumab and pertuzumab or trastuzumab alone. The trial showed that there is a significant benefit to the addition of pertuzumab for higher-risk cancers.

For stage I HER2-positive breast cancer, paclitaxel and trastuzumab can be used. A 400-patient prospective study led by Sara Tolaney, MD, of Dana-Farber Cancer Institute, examined that regimen and demonstrated a very low risk of recurrence of less than 4% in women who received the combination. For higher-stage cancers, physicians will add more chemotherapy and anti-HER2 drugs, states Burstein.

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Dr. Burstein on the Treatment Landscape of HER2+ Breast Cancer

Harold J. Burstein, MD, PhD, senior physician, associate professor of medicine, Harvard Medical School, Dana-Farber Cancer Institute, discusses the results of the APT trial investigating adjuvant paclitaxel and trastuzumab (Herceptin) for node-negative HER2-positive breast cancer. 

The APT trial was an adjuvant study investigating 400 women with stage I HER2-positive breast cancer. The patients received treatment with trastuzumab and paclitaxel. There was a 97% 5-year disease-free survival showing encouraging results, states Burstein. 

Harold J. Burstein, MD, PhD, senior physician, associate professor of medicine, Harvard Medical School, Dana-Farber Cancer Institute, discusses the results of the APT trial investigating adjuvant paclitaxel and trastuzumab (Herceptin) for node-negative HER2-positive breast cancer.

Dr. Burstein on the Results of the APT Trial for HER2+ Breast Cancer

Harold J. Burstein, MD, PhD, senior physician, associate professor of medicine, Harvard Medical School, Dana-Farber Cancer Institute, discusses the 7-year follow-up of the APT trial investigating adjuvant paclitaxel and trastuzumab (Herceptin) for node-negative HER2-positive breast cancer.

In the initial results, there was a disease-free survival of 97%, explains Burstein. Those results were validated following the 7-year follow-up. Additionally, the instance of distant metastatic recurrence is low.

These follow-up results demonstrate that the patients on this trial have seen significant benefits, states Burstein.

Dr. Burstein on the Follow-Up of APT Trial for HER2+ Breast Cancer

Harold J. Burstein, MD, PhD, Senior Physician, Associate Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute discusses the results of MONARCH1, which looked at abemaciclib as monotherapy in patients with ER-positive breast cancer, after chemotherapy for advanced disease.

CDK4/CDK6 inhibitors, like abemaciclib, are a new class of drugs being investigated in advanced ER-positive breast cancer, said Burstein

In the study, the drug was shown to be reasonably well tolerated with some mild neutropenia and some incidence of lower GI-toxicity and diarrhea.

Abemaciclib induced a response rate of 19% in this patient population. The median progression-free survival (PFS) was six months and the median overall survival (OS) was 17.7 months.    

​Harold J. Burstein, MD, PhD, Senior Physician, Associate Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute discusses the results of MONARCH1, which looked at abemaciclib as monotherapy in patients with ER-positive breast cancer, after chemotherapy for advanced disease.

Dr. Harold J. Burstein on CDK4/CDK6 Inhibitor Abemaciclib in Breast Cancer

Harold J. Burstein, MD, PhD, Associate Professor of Medicine, Harvard Medical School, Medical Oncology/Solid Tumor Oncology, Dana-Farber Cancer Institute, discusses the use of pathological complete response (pCR) in the ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization) trials, which randomized patients into 3 different trial designs, each with 4 treatment arms that received lapatinib (Tykerb), trastuzumab (Herceptin), or both in the adjuvant and neoadjuvant setting.

Multiple studies have shown that pCR in the neoadjuvant setting indicates a better overall outcome in breast cancer patients. The use of pCR is not yet to the stage where it can be used as a surrogate endpoint for the approval of new drugs or to establish a new standard of care but it can work as a measurement of treatment efficacy. Despite the push towards its use, it has not translated into major gains in disease free survival (DFS), in prospective trials.

The pairing of the results from the NeoALTTO and the full ALTTO trial remains an important comparator for determining if pCR works as a predictive marker for disease free survival. The NeoALTO trial results were promising (

) and demonstrated a great deal about pCR, if these findings are echoed in the rest of the ALTTO trial it will go a long way towards using this endpoint in future trials.

Other investigations suggest that pCR has no effect on outcomes for HER2-positive estrogen receptor (ER)-positive cancers suggesting that the ability of pCR to predict response is limited by ER status. The NeoALTTO trial demonstrated that the pCR rate was higher in patients with HER2-positive ER-negative than those that were ER-positive. It remains unclear if pCR is significant in ER-positive cancer, which comprises approximately 50% of HER2-positive cancers.

Dr. Harold Burstein, from the Dana-Farber Cancer Institute, Discusses Pathological Complete Response

Harold J. Burstein, MD, PhD

Articles

Dr. Burstein on the Treatment Landscape of HER2+ Breast Cancer

Dr. Burstein on the Results of the APT Trial for HER2+ Breast Cancer

Dr. Burstein on the Follow-Up of APT Trial for HER2+ Breast Cancer

Dr. Harold J. Burstein on CDK4/CDK6 Inhibitor Abemaciclib in Breast Cancer

Dr. Burstein on Pathological Complete Response