Breast Cancer Meeting 'Is Going to Be Spectacular'

Nick Mulcahy

December 03, 2019

The 2019 version of the San Antonio Breast Cancer Symposium (SABCS) is exceptionally well stocked with important research and presentations, according to Carlos Arteaga, MD, co-director of the meeting and director of Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas.

"The meeting is going to be spectacular this year," he told Medscape Medical News.

Arteaga highlighted areas of research that collectively contain some of the most important findings: clinical trials featuring novel systemic therapies for HER2-positive disease, neoadjuvant trials with checkpoint inhibitors, and new data on the clinical implications of residual disease after neoadjuvant therapy.

The meeting runs from December 10 to 14 at San Antonio's Henry Gonzalez Convention Center.

When asked to name a single presentation that will likely generate a lot of buzz among clinicians at the meeting, Arteaga said, "I'm not a sociologist." But he sportingly offered a few guesses, including an oral paclitaxel study. Phase 3 study investigators will update data released earlier on progression-free and overall survival of the new oral form vs the old IV form of the drug in advanced disease; paclitaxel is the most commonly used chemotherapy in breast cancer, Arteaga observed.

Wednesday's Session

The meeting's first general session is on Wednesday, December 11, and features a series of studies examining the use of novel treatments for HER2-positive disease.

The phase 3 HER2CLIMB trial evaluates the investigational agent tucatinib (Seattle Genetics) vs placebo (both combined with capecitabine and trastuzumab) for patients with pretreated HER2-positive metastatic breast cancer with and without brain metastases. Brain mets are difficult to treat with systemic therapy because the blood-brain barrier blocks the passage of larger sized molecules; notably, tucatinib is a small-molecule tyrosine kinase inhibitor. The study was highlighted by a podium presenter at the recent Advanced Breast Cancer 5 conference in Lisbon, Portugal, who said to "stay tuned" for more at SABCS.

Phase 2 study data will be presented on the novel antibody drug conjugate (ADC) trastuzumab deruxtecan (AstraZeneca and Daiichi Sankyo) in patients with refractory HER2-positive metastatic breast cancer previously treated with the currently approved ADC, T-DM1. Also, there will be new overall survival data from the phase 3 SOPHIA study of margetuximab (MacroGenics) in patients with HER2-positive metastatic breast cancer after prior anti-HER2 therapies; the investigational monoclonal antibody is "slightly different" than trastuzumab, Arteaga observed.

"The cumulative excitement about this [session] is that these trials provide additional approaches to target HER2 that may herald a time in which the HER2-positive disease subtype is eliminated," he proclaimed.

Arteaga explained that if one, two, or three new drugs are developed that work in very late HER2-positive disease and can eventually be moved to the adjuvant setting, then "eventually we are going to dial up the cure rate."

Eventually we are going to dial up the cure rate. Dr Carlos Arteaga

Even with the current treatment choices, clinicians in developed nations are seeing fewer and fewer patients with HER2 disease that has progressed to the metastatic stage. "They are harder to find because we are curing them," Arteaga said.

"It's very exciting" because not long ago, "we thought there was no room for additional drug development" in this disease subtype, he added.

This initial Wednesday session will also include an interim overall survival analysis of the APHINITY (BIG 4-11) trial, which Arteaga called a "seminal trial that has already set the standard of care with adjuvant therapy" in patients with operable HER2-positive early breast cancer. Investigators will update outcomes from the trial, which compares chemotherapy plus trastuzumab plus pertuzumab with chemotherapy plus trastuzumab plus placebo.

Thursday and Friday Highlights

On Thursday morning, general session 3 will feature trials employing immunotherapies including atezolizumab, pembrolizumab, and durvalumab for breast cancer. To date, there have been mixed results with this approach — and that disallows too much optimism, said Arteaga. "It's not something where we can join hands and sing Kumbaya — it's something we have to think about."

Later in the day, at general session 4, there will be new long-term results from a number of major clinical trials, including 5-year, clinical treatment score validation data from the landmark TAILORx trial. And there will also be 10-year follow-up results from a European randomized phase 3 trial of accelerated partial- or whole-breast irradiation after breast conservation surgery for patients with early breast cancer.

On Friday morning, at general session 5, multiple studies will focus on neoadjuvant therapy, which is "probably going to become the norm in terms of cancer care," said Arteaga.

Traditionally, surgery has been the first treatment for breast cancer — and adjuvant therapies followed. However, Arteaga pointed out that the neoadjuvant approach has multiple advantages, such as allowing for breast conservation therapy (instead of mastectomy when systemic therapy shrinks or disappears a tumor) and providing additional prognostic information via pathological complete response or lack thereof.

"One day, breast cancer will probably be treated like lymphomas. Lymphomas used to be operated on — which is the craziest thing you could do," he said. "Eventually, as effective systemic treatments were developed and used early, lymphomas were not operated on anymore."

Coincidentally this general session will feature an interim analysis of the MICRA trial (Minimally Invasive Complete Response Assessment), which omits breast surgery in some patients with pathologic complete response after neoadjuvant systemic therapy.

"Yes, we now have clinical trials that are piloting the idea of not operating on some patients," said Arteaga.

The session will also feature multiple presentations on the clinical implications of residual disease after neoadjuvant therapy, including a multicenter pooled analysis looking at long-term survival.

Artega has disclosed no relevant financial relationships.

2019 San Antonio Breast Cancer Symposium. Presented December 10-14, 2019.

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