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ASCO 2024: Breast Cancer Trial Updates and Takeaways

By BCRF | July 1, 2024

Plus, BCRF investigators recognized with top awards at the annual meeting

The American Society of Clinical Oncologists (ASCO) held its largest annual meeting to date with more than 44,000 participants, 200 sessions, and 7,000 abstract presentations. BCRF was well represented, with many of our investigators taking center stage to present recent results and leading sessions and panels with their colleagues.

Here, we highlight some of the breast cancer developments featured at ASCO and congratulate BCRF investigators who received awards at the conference.

Antibody-drug conjugates a major focus

The antibody-drug conjugate trastuzumab deruxtecan (T-DXd/Enhertu®) made headlines at ASCO 2022 when researchers presented practice-changing results from the DESTINY-Breast04 trial showing that this HER2-targeted ADC provided significant improvements in survival for patients with HER2-low metastatic breast cancer (MBC) over chemotherapy. At this year’s meeting, researchers presented the results from ongoing trials further evaluating T-DXd.

Dr. Giuseppe Curigliano of the European Institute of Oncology presented the data from DESTINY-Breast06. This study showed that T-DXd slows cancer growth for longer than chemotherapy in people with hormone receptor (HR)–positive/HER2-low or -ultralow MBC that progressed after endocrine therapy (90.4 percent of the participants also received a CDK4/6 inhibitor). HER2-low and -ultralow are designations that indicate the amount of HER2 protein present on tumor biopsy samples based on immunohistochemistry (IHC) staining: HER2-low cells are IHC 1+ or 2+ and HER2-ultralow cells are IHC 0 to 1+ as judged by a pathologist.

Patients with HER2-low MBC had a median progression-free survival (PFS or length of time during or after treatment where the disease does not get worse) of 13.2 months with T-DXd versus 8.1 months with chemotherapy. And similar results were reported in patients with HER2-ultralow MBC. The investigators also examined patients’ objective response rates (ORR) which are determined by using several techniques to measure how a tumor changes with treatment: Does it shrink, stay the same, or exhibit a decrease in metabolism?

They found that ORR was higher for those who received T-DXd: In patients with HER2-low MBC, the ORR was 56.5 percent compared to 32.3 percent with chemotherapy; in HER2-ultralow MBC, the ORR was more than doubled with T-DXd (61.8 percent) compared to chemotherapy (26.3 percent). Importantly, patients were able to stay on T-DXd treatment longer—median treatment length of 11 months versus 5.6 months with chemotherapy—without additional side effects.

BCRF investigator Dr. Fabrice André presented the phase 1b/2 multicenter DESTINY-Breast07 trial comparing T-DXd alone and in combination with pertuzumab (Perjeta®) in HER2-positive MBC. He and his colleagues found similar responses as reported in DESTINY-Breast06, demonstrating a 77.3 percent ORR with T-DXd alone compared to 82 percent with T-DXd plus pertuzumab. At 12 months, the PFS rates were 77.3 percent with T-DXd and 89.4 percent with the combination treatment. Moreover, no new toxicities were observed for each treatment. These results represent one part of a complex, multi-pronged study, and analysis is ongoing.

Dr. Binghe Xu of the Chinese Academy of Medical Sciences Cancer Hospital reported findings from the phase 3 OptiTROP-Breast01 trial testing a novel TROP2-targeting ADC (sacituzumab tirumotecan/sac-TMT) versus standard-of-care chemotherapy in heavily pre-treated advanced triple-negative breast cancer (TNBC). The primary endpoint for this analysis was PFS: The median PFS in patients receiving sac-TMT was 5.7 months compared to 2.6 months in patients receiving chemotherapy.

The first planned interim analysis of overall survival (OS or the time from diagnosis or treatment where the patient survives) also showed a significant benefit for sac-TMT (57.8 percent in patients on sac-TMT compared to 35.2 percent with chemotherapy) after a 10.4-month follow-up; and ORRs were 43.9 percent with sac-TMT and 12.8 percent with chemotherapy. This study suggests that sac-TMT may be an effective treatment option for pre-treated TNBC, potentially expanding treatment options for this aggressive subtype with limited choices.

The Trop2 ADC datopotamab deruxtecan (Dato-DXd), which targets a tumor-associated protein called Trop2, was tested in the TROPION-Breast01 trial in patients with previously treated inoperable or metastatic HR-positive/HER2-negative breast cancer. BCRF investigator Dr. Aditya Bardia and his team presented patient-reported outcomes data that showed improvements in quality-of-life measures with Dato-DXd treatment compared to chemotherapy. This trial is ongoing but these early findings regarding Dato-DXd’s tolerability support this ADC as a potential new therapeutic option in this setting.

ADCs have changed the treatment landscape for advanced HR-positive breast cancers that become resistant to hormone-targeting agents. Their success has propelled research to expand the list of ADC targets and develop new ADCs to give patients more options.

Noteworthy studies build on results testing CDK4/6 inhibitor added to endocrine therapy

The global monarchE trial showed that invasive disease–free survival was significantly improved when adjuvant (post-surgery) abemaciclib (Verzenio®), a CDK4/6 inhibitor, was added to endocrine therapy in HR-positive/HER2-negative, node-positive, high-risk early breast cancer.

BCRF investigator Dr. Sherene Loi reported the prognostic utility of circulating tumor DNA (ctDNA) in a subset of patients from the monarchE trial. This exploratory analysis showed that patients that had detectable ctDNA (ctDNA-positive) at the start of the study experienced worse outcomes of any group. And those who remained persistently ctDNA-positive or became positive after treatment were more likely to experience a recurrence event compared to those who persistently had no detectable ctDNA (ctDNA-negative) or remained negative. Those who became ctDNA-negative after treatment also had more favorable outcomes, regardless of treatment. These findings suggest that ctDNA clearance could become a noninvasive surrogate to monitor response to neoadjuvant (pre-surgery) therapy.

BCRF investigator Dr. Kevin Kalinsky reported preliminary analyses of the postMONARCH trial, a phase 3 study of abemaciclib plus fulvestrant (Faslodex®) versus fulvestrant alone in patients with metastatic HR-positive/HER2-negative breast cancer that had progressed on a prior CDK4/6 inhibitor and endocrine therapy. This study showed that abemaciclib plus fulvestrant significantly improved PFS compared to fulvestrant alone (5.6 months versus 3.9 months). Moreover, these results were consistent regardless of ESR1 mutation status or PI3K pathway alterations. These results demonstrate the utility of continued CDK4/6 inhibition after progression on a prior CDK4/6 inhibitor in advanced breast cancer. Further analysis is underway.

Intervention to improve clinical outcomes

Obesity increases a person’s risk of breast cancer recurrence and mortality, so researchers are interested in developing strategies to induce weight loss and potentially improve clinical outcomes.

BCRF investigator Dr. Neil Iyengar presented results from an ongoing study investigating the feasibility and efficacy of a personalized diet and exercise program on weight and body composition in 43 postmenopausal patients with a BMI of 27 or greater and primary HR-positive breast cancer treated with endocrine therapy. Participants received calorie-restricted plant-based meals and were directed to walk on a treadmill and burn 250 calories three to five days a week.

Patients in the intervention arm achieved a mean weight loss of 13 percent compared with five percent in the control group. This study was unique in that weight loss was not the only parameter examined. The group looked at mean fat loss and found that the intervention group decreased their body fat content by 6 kg (13.2 pounds) compared with 2 kg (4.4 pounds) in the control group. Increases in lean mass were greater in the intervention group and no serious adverse effects were observed. These results demonstrate that a personalized, calorie-restricted plant-based diet plus exercise can lead to substantial weight loss and favorable changes in body composition during endocrine therapy for HR-positive breast cancer. Studies are ongoing to determine if there is a correlation between these results and the biology of patients’ tumor samples.

Long-term follow-up shows promise for pregnancy after breast cancer

BCRF investigator Dr. Ann Partridge has led a number of studies focused on managing breast cancer in younger women. She leads the Young Women’s Breast Cancer Study, a multicenter, prospective observational trial in women 40 and younger who are newly diagnosed with stage 0 to 3 breast cancer. Study participants (1,302 women enrolled to date) are surveyed every six months during the first three years after their diagnosis, and then annually for an additional seven years. Investigators assess short and long-term disease and treatment issues, tumor biology and its relationship to patient outcomes, and psychosocial concerns.

One of the unique concerns this patient population faces is fertility preservation, particularly since certain cancer treatments can have a temporary or permanent impact on a woman’s ability to become pregnant. At ASCO, the study team reported the subgroup analysis of 197 participants who reported attempting pregnancy after diagnosis. Of these patients, 73 percent became pregnant at least once, and nearly two out of every three reported having at least one full-term pregnancy. The median follow-up was 11 years, and patients reported that time from diagnosis to a first pregnancy was about four years. 

This is the first prospective study with more than a ten-year follow-up to report fertility outcomes in younger patients with breast cancer. These encouraging initial results hold promise for younger patients with breast cancer who hope to have a baby in the future. 

BCRF investigators receive awards

Two BCRF investigators received top awards at this year’s ASCO meeting. Dr. Lori Pierce received the 2024 Excellence in Equity Award which is endowed by the American Cancer Society. This award is given in recognition of ASCO members who have worked to make oncology more equitable, diverse, and inclusive or who have strived to facilitate equitable access to care.

The Gianni Bonadonna Breast Cancer Award endowed by GlaxoSmithKline Oncology was given to Dr. Lisa Newman. This award recognizes a clinical researcher who has an established record in the field of breast cancer and has made significant contributions to mentor the next generation of researchers.