The San Antonio Breast Cancer Symposium (SABCS) 2021 will “be a great meeting,” according to Carlos Arteaga, MD, director of Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas.
Arteaga, the meeting’s co-director, said the first-ever hybrid symposium will take place virtually from December 7 to 10 as well as in person. Online availability appears to be a boon to attendance, with a record 9325 registrants for the 2020 symposium, held only virtually due to the COVID-19 pandemic.
The meeting will have an app available, which can be accessed by searching “San Antonio Breast Cancer Symposium” (Google Play for Android, Apple for iOS) and downloading, or by clicking here from a desktop computer.
Arteaga provided a sneak peek of the most exciting research being presented at the upcoming meeting.
On the Horizon for Advanced Breast Cancer
A “very important” study of an investigational oral agent employed in heavily pretreated postmenopausal women with estrogen receptor–positive (ER+) advanced breast cancer headlines the meeting.
This international, multicenter trial could have “practice-changing implications,” Arteaga told Medscape Medical News.
The phase 3 EMERALD trial (abstract GS2-02) pits elacestrant, a selective estrogen receptor degrader (SERD), against standard endocrine therapy (fulvestrant or an aromatase inhibitor) in patients with metastatic breast cancer whose disease has progressed after treatment with at least one endocrine therapy and a CDK4/6 inhibitor.
The trial is important because many patients with breast cancer have estrogen receptor mutations, which are a “major mechanism of [drug] resistance” and thus progression on earlier therapy, Arteaga said.
Elacestrant is in good company among a plethora of oral SERDs under investigation in advanced breast cancer; however, currently, fulvestrant — which requires an intramuscular injection in the buttocks every month — is the only approved SERD.
“There’s plenty of preclinical data that suggest that these drugs [SERDs] may have activity against these mutant forms of the receptor, which occur in up to 40% of patients with advanced ER+ breast cancer,” he explained.
Researchers will present data on two primary outcome measures from the phase 3 trial: progression-free survival (PFS) based on mutations of the estrogen receptor 1 gene (ESR1-mut) and PFS in all subjects regardless of ESR1 status.
In addition to the EMERALD trial, PADA-1 (abstract GS3-05) is another important randomized, phase 3 trial focused on treating estrogen receptor mutations in patients with metastatic disease, said Arteaga.
The trial has enrolled patients with ER+ metastatic breast cancer who received an aromatase inhibitor (letrozole, anastrozole, or exemestane) and the CDK 4/6 inhibitor palbociclib as first-line therapy.
In step 1 of the trial, approximately 1000 patients were screened for circulating blood ESR1 mutation detection at regular intervals while being treated with palbociclib and an aromatase inhibitor in a continuous scheme until tumor progression or ESR1 mutation detection.
In step 2, up to 200 patients with a rising circulating ESR1 mutation and no tumor progression were randomized 1:1 to no change in therapy until tumor progression or to receive palbociclib plus fulvestrant until tumor progression.
The trial examines the safety and efficacy of “a clinical conundrum that we face” in this setting: whether or not to switch treatment from an aromatase inhibitor to fulvestrant while continuing a CDK 4/6 inhibitor at the sign of mutation detection, Arteaga explained.
Refining Who Gets the “Kitchen Sink”
Arteaga also highlighted two trials focused on the immune checkpoint inhibitor pembrolizumab.
The phase 3 KEYNOTE-522 study led to the approval of neoadjuvant pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer (TNBC) in July 2021. At this year’s SABCS, researchers will present new data from KEYNOTE-522 (abstract GS1-01), representing final results from the trial’s event-free survival (EFS) outcome.
Previously, investigators reported a statistically significant and clinically meaningful improvement in EFS. These data suggest “that deploying immunotherapy early before surgery…may be curative in some patients,” Arteaga said. The new data will allow the “robustness and consistency” of the earlier findings to be assessed.
But, he added, this is a “tough” treatment, which includes five drugs. “It’s the kitchen sink, and not everybody needs the kitchen sink. It’s important to refine these findings. Some patients may not need pembrolizumab, but some do.”
The second trial exploring pembrolizumab — KEYNOTE-355 (abstract GS1-02) — mirrors KEYNOTE-522 but in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1.
Previously, investigators reported that pembrolizumab combined with chemotherapy showed statistically significant improvements in overall survival and PFS compared to placebo plus chemotherapy. At the 2021 SABCS, researchers will provide final study results, including outcomes in subgroups of patients by additional combined positive score cutoffs.
Metformin Trial: “This Is It”
Arteaga also highlighted CCTGMA.32 (abstract GS1-08), a phase 3 randomized, placebo-controlled adjuvant trial of the diabetes drug metformin vs placebo in early breast cancer. Results of the primary efficacy analysis of the trial will be presented at the meeting.
The Canadian-led study seeks to determine if metformin can decrease breast cancer cell growth and work with cancer therapies to prevent disease recurrence. The study design calls for patients to take twice-daily oral metformin or placebo pills for up to 5 years in the absence of disease progression.
The primary outcome of the 3500-plus patient trial is invasive disease-free survival in hormone receptor (ER and PgR) negative and positive (ER and/or PgR) subgroups.
“Metformin has actually been associated with improved survival [in breast cancer] in patients on chemotherapy. But we don’t know exactly how,” he said. “There’s never been a head-to-head comparison in the adjuvant setting [before]. This is it.”
TKI for Breast Cancer With Brain Mets
The SABCS co-director also spotlighted an updated overall survival analysis of the randomized phase 3 PHOEBE trial (abstract GS3-02).
Previous research confirmed the superiority of pyrotinib, a novel TKI targeting HER1, HER2, and HER4, over lapatinib when given in combination with capecitabine in HER2-positive metastatic breast cancer.
In the US, the lapatinib-capecitabine combination is “mostly used” in patients with HER2 metastatic disease and brain metastases who also undergo stereotactic radiation, Arteaga said.
This use has continued despite groundbreaking results from the HER2CLIMB trial, featuring the TKI tucatinib, he said.
As reported last year, adding tucatinib to trastuzumab and capecitabine in patients with HER2-positive breast cancer and brain metastases increased median overall survival from 12 months to 18.1 months. The results were called the first of their kind at that time.
The pyrotinib study may matter to American clinicians because pyrotinib is used mostly in China, not the US, and this analysis suggests that pyrotinib could be part of the armamentarium in the US, alongside tucatinib.
TKIs are like Coke and Pepsi, Arteaga said: “Similar but not identical.” Therefore, it is worth taking a look at the new study, he said. “There may be some benefit in having more than one [TKI] in the therapeutic armamentarium.”
Arteaga receives or has received grant support from Pfizer and Lilly and serves or has served in a scientific advisory role with Novartis, Lilly, TAIHO Oncology, Daiichi Sankyo, Merck, AstraZeneca, OrigiMed, Immunomedics, ARVINAS, Sanofi, Athenex, and the Susan G. Komen Foundation. He also holds minor stock options from Provista.
San Antonio Breast Cancer Symposium (SABCS) 2021. December 7–10.
Nick Mulcahy is an award-winning senior journalist for Medscape, focusing on oncology, and can be reached at [email protected] and on Twitter: @MulcahyNick