What's Hot at SABCS 2018

Pam Harrison

November 27, 2018

SAN ANTONIO — Treatment duration, optimal sequencing strategies, and the usefulness of giving upfront endocrine therapy prior to surgery are all on the agenda at the 41st annual San Antonio Breast Cancer Symposium (SABCS), to be held December 4-8.

On the second day of the meeting, researchers will present final results of the PHARE trial (GS2-07), which assessed 6 months of trastuzumab treatment (Herceptin; Genentech) vs the standard 12-month regimen in HER2-positive breast cancer.

"It’s not so much that 'less is more,' it’s rather that less may be similar but a shorter treatment course is less costly and has fewer side effects," Kent Osborne, MD, SABCS co-director and director of the Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas told Medscape Medical News.

Kent Osborne, MD

"De-escalation of treatment is now a major theme now in breast cancer therapy," he added.

De-escalation is vitally important, agreed Carlos Arteaga, MD, SABCS codirector and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center in Dallas, Texas.

Carlos Arteaga, MD

"In general, we treat too many patients with too many drugs and for too long," he told Medscape Medical News in an email.

"There is an increasing understanding that many patients may not need the full intensity of these therapies." 

In general, we treat too many patients with too many drugs and for too long Dr Carlos Arteaga

This issue will be examined in a major meta-analysis (GS3-03) that evaluates whether  prolonging adjuvant aromatase inhibitor (AI) therapy beyond 5 years reduces the risk for recurrence and improves cancer-specific mortality compared with 5 years alone. 

The meta-analysis involves nearly 25,000 women and represents a pooling together of 12 randomized controlled trials. "This will be the most definitive answer yet [to this question]," Osborne said.

Another important study (GS2-04) asks whether administering adjuvant capecitabine (Xeloda; Genentech) after standard chemotherapy for the treatment of early-stage, triple-negative breast cancer improves overall survival (OS) in patients with residual disease.

The KATHERINE trial (GS1-10) compares trastuzumab emtansine (T-DM1) (Kadcyla; Genentech) to standard trastuzumab, with each given as adjuvant therapy in patients with HER2-positive early-stage breast cancer after neoadjuvant chemotherapy and HER2-targeted therapy.

Importantly, T-DM1 is less toxic than traditional chemotherapy, said Osborne.

Previous trials showed that T-DM1, an antibody-drug conjugate, improved both progression-free and OS in the setting of metastatic, HER2-positive breast cancer.

The PALLET trial (GS3-02) compares the neoadjuvant use of letrozole (Femara; Novartis) plus palbociclib (Ibrance; Pfizer), a selective inhibitor of the cyclin-dependent kinases CDK4/CDK6, to letrozole alone in patients with estrogen receptor–positive, HER2-negative breast cancer.

Osborne noted that this type of approach rarely eradicates any tumor completely such that patients don’t need surgery.

"However, it could make the tumor smaller so patients may be able to have a lumpectomy rather than a mastectomy," he observed.

Ian Smith, MD, from the Royal Marsden Hospital in London, England, will be discussing this very drug therapy approach during the McGuire Memorial Lecture on December 5. His institution has been a pioneer in the development and popularization of neoadjuvant endocrine therapy.

Biomarkers and Treatment

One of the ways that de-escalation of treatment has been made possible is through the use of biomarkers that identify which groups of patients will most likely benefit from treatment  and which ones will not.

To this end, efficacy data based on patients’ biomarker profiles from the IMpassion130 trial (GS1-04) may or may not help oncologists better identify which groups of patients with metastatic, triple-negative breast cancer will most likely benefit from the combination of atezolizumab (Tecentriq; Genentech) and nab-paclitaxel (Abraxane; Celgene).

In an earlier report, efficacy results from IMpassion130 indicated that the combination of immunotherapy plus chemotherapy appeared to extend OS compared with standard chemotherapy alone, especially among patients whose tumors expressed PD-L1.

In another examination by researchers, results will be presented on a study of the sequencing of breast cancer predisposition genes in close to 20,000 breast cancer patients and over 20,000 matched unaffected controls (GS2-01).

Osborne said this analysis of a very large patient database could allow researchers to identify not just known genes for breast cancer, such as BRCA1 and BRCA2, but potentially other genes related to breast cancer risk.

Important trials in radiation therapy will be presented.

For example, researchers will present 10-year follow-up results from the EORTC AMAROS trial (GS4-01) comparing short-term, radiotherapy vs surgery of the axilla in breast cancer patients with a positive sentinel node.

Investigators will also be presenting results on studies evaluating regional lymph node irradiation in early-stage breast cancer (GS4-02); accelerated partial radiation of the breast (GS4-03); conventional whole breast irradiation vs partial breast irradiation for women with stage 0, I or II breast cancer (GS4-04); and dose-escalated boost radiotherapy for women treated with breast conservation surgery in the setting of early-stage breast cancer (GS4-05). 

In addition, investigators will be looking at the effects that exercise training have on cardiovascular function while patients are undergoing adjuvant treatment (GS5-02), as well as the effect that lifestyle intervention may have on disease-free survival (GS5-03).

"Breast cancer is the most common cancer in women and the second [leading] cause of cancer-related death, the first one being lung cancer, and advances in the field are many and keep coming faster," Arteaga observed.

Osborne and several Baylor College of Medicine colleagues founded the SABCS in 1978. At the time, the symposium was intended only for oncologists in and around San Antonio, and expert speakers were invited.

Then, in the early 1980s, organizers invited scientists to submit abstracts and asked the authors of the best papers to present their research at the meeting.

"That’s when the meeting really took off," Osborne recalled.

"So we’ve gone from about 75 local people who attended the first meeting to where we now get about 8000 people from all over the world, so the meeting has grown logarithmically since then," he said.

Osborne has received grant support from Puma Biotechnology and has served on the advisory board for Tolmar Pharmaceuticals and a data monitoring committee for a clinical trial done by Eli Lilly. 

Arteaga has disclosed no relevant financial relationships.

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