What's Cool at the San Antonio Breast Cancer Symposium

Nick Mulcahy

December 03, 2015

There is "no real blockbuster study" at next week's San Antonio Breast Cancer Symposium (SABCS), but there are a multitude of presentations that will potentially expand clinical understanding and improve care, said C. Kent Osborne, MD, director of the Dan L. Duncan Comprehensive Cancer Center at the Baylor College of Medicine in Houston.

He would know. Dr Osborne, who is a long-time breast cancer specialist, has been involved with the meeting since 1978 and, as he has been since 1992, is a director of the gathering again this year.

This year's meeting will feature notable studies on chemotherapy combinations for HER2-positive disease, targeted therapy for metastatic disease with a specific mutation, long-term outcomes of different surgeries for early-stage cancers, and the first-ever trial of a RANKL inhibitor as an adjuvant treatment for breast cancer in postmenopausal women.

Dr Osborne discussed these and other presentations with Medscape Medical News in advance of 5-day meeting, which starts December 8.

He kicked off his comments by highlighting a presentation of 10-year results from the controversial Breast Cancer International Research Group (BCIRG) 006 study, which has helped establish the benefit of trastuzumab (Herceptin, Roche) in patients with HER2-positive early-stage breast cancer, and assesses the targeted agent in combination with an anthracycline-containing regimen (doxorubicin [Adriamycin], cyclophosphamide, and docetaxel) and with a nonanthracycline regimen (docetaxel and carboplatin).

The BCIRG 006 trial, which involves more than 3000 women, addresses the critical question of whether adjuvant anthracyclines are necessary for the treatment of HER2-positive breast cancer. Five-year data from the study were published in 2011 (N Engl J Med. 2011;365:1273-1128).

BCIRG 006 investigator Dennis Slamon, MD, PhD, from the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, has repeatedly interpreted the interim results as indicating that anthracyclines are mostly unnecessary in this setting and more toxic, especially with regard to the heart. However, other experts have argued that anthracyclines, which are a backbone of systemic breast cancer treatments, are a strong option, as reported by Medscape Medical News.

"To date, carboplatin plus trastuzumab has looked almost as good but less toxic," summarized Dr Osborne, who added that both regimens in the study are a standard of care. The new data might provide further clarity about efficacy and safety, he said.

The MANTICORE (Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research) trial is another study of patients with HER2-positve early-stage breast cancer. It is the first randomized controlled study to evaluate the use of antihypertensive agents for the prevention of cardiac damage associated with trastuzumab treatment, which is a problem in these patients, Dr Osborne reported.

The MANTICORE researchers are assessing whether 1 year of treatment with the ACE inhibitor perindopril or the beta-blocker bisoprolol can prevent the left ventricular remodeling (measured with MRI) associated with 1 year of trastuzumab therapy.

The meeting will also feature an oral presentation on an early-phase trial of the investigational checkpoint inhibitor avelumab (Pfizer). Response rates with the immunotherapy will be reported in patients with locally advanced or metastatic breast cancer refractory to or progressing after standard-of-care therapy. The study involves patients with HER2-negative estrogen receptor (ER)-positive disease, HER2-negative ER-negative disease, triple-negative disease, or HER2-positve disease.

Metastatic breast cancer that is ER-positive and HER2-negative is the subject of the placebo-controlled phase 3 SANDPIPER trial of the experimental PI3-kinase inhibitor taselisib (Genentech/Roche), which is used in combination with the selective ER-degrader fulvestrant (Faslodex, AstraZeneca).

All of the SANDPIPER patients are postmenopausal and have had disease recurrence or progression after treatment with an aromatase inhibitor. And they all have a PIK3CA mutation, which is one of the most frequent genomic alterations in breast cancer, and is present in about 40% of HER2-negative ER-positive tumors.

PIK3CA mutations promote the growth and proliferation of tumors and mediate resistance to endocrine therapies.

"We have a lot of data that endocrine resistance upregulates other pathways," Dr Osborne explained. Taselisib targets one particular intracellular signaling pathway (PI3K) that is associated with endocrine resistance.

Interim data from the SANDPIPER trial will be presented by Jose Baselga, MD, from the Memorial Sloan Kettering Cancer Center in New York City.

The first trial examining adjuvant denosumab (Xgeva, Amgen) as a treatment for breast cancer will be presented by Michael Gnant, MD, from the Medical University of Vienna in Austria.

The phase 3 ABCSG-18 clinical trial compares denosumab with placebo in combination with adjuvant aromatase inhibitor therapy in 3000-plus postmenopausal women with early-stage hormone-receptor-positive breast cancer.

Denosumab is approved as a treatment to increase bone mass in breast cancer patients receiving endocrine therapy who are at high risk for fracture. But the new data will be about denosumab as a cancer therapy, not a bone-building agent.

Dr Osborne explained that there is already evidence that bisphosphonates, another type of bone-building agent, are an effective adjuvant treatment. They produce a reduction in the recurrence rate of about 30% in postmenopausal women with early-stage disease.

If the data on denosumab, which is the first-in-class RANKL inhibitor, are positive, "it's going to be hard to deny use of one of the two strategies in patients," he said.

New results from an observational Dutch study will provide more survival data on patients with early breast cancer treated with lumpectomy plus radiation or mastectomy alone.

The results are long-term — 10 years, Dr Osborne reported, which will be helpful to clinicians in discussions with patients about the merits and shortcomings of the two approaches.

The data for the study come from the Netherlands Cancer Registry. The country is especially well suited for an analysis of this type because there are only a few cancer treatment hospitals in the country, and "they all work together well," said Dr Osborne.

Dr Osborne has disclosed no relevant financial relationships.


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