The European Society for Medical Oncology’s annual meeting explored next-generation treatments for metastatic breast cancer and triple-negative breast cancer
Key Takeaways
- The annual meeting of the European Society for Medical Oncology (ESMO) took place last week.
- Breast cancer researchers shared updates on clinical trials involving CDK4 inhibitors and ADCs in the metastatic setting including metastatic triple-negative breast cancer.
- Read on to find out more about the highlights from the meeting.
The annual meeting of the European Society for Medical Oncology (ESMO) took place in Madrid last week. The virtual event gathered over 40,000 researchers and advocates from across the globe. This year’s meeting highlighted several areas of progress in breast cancer research.
From new treatments for metastatic breast cancer, including triple-negative breast cancer brain metastases to positive clinical trial updates, ESMO was rich in promising news for patients.
Here are a few noteworthy developments.
New and next-generation treatments for metastatic breast cancer
Metastatic breast cancer (MBC) remains an important focus for researchers as it is still not curable. Treatment for hormone receptor (HR)-positive, HER2-negative MBC typically includes a combination of CDK4/6 inhibitor and hormone therapy. However, over time, many tumors become resistant to this treatment, so researchers are looking for strategies to prevent this and/or develop other treatment options.
Phase 2 FOURLIGHT-1 trial
Researchers at ESMO shared their findings from the phase 2 FOURLIGHT-1 trial. Researchers tested a new CDK4 inhibitor, atirmociclib, in combination with Faslodex (fulvestrant) in patients who had received prior CDK4/6 inhibitor treatment. CDK4/6 inhibitors are oral medications used to treat some types of HR-positive breast cancer, and Faslodex is a hormone therapy. This targeted therapy homes in on the gene CDK4, part of a protein family that helps cancer cells grow and divide.
Results showed that this combination extended progression-free survival to 9.4 months compared to 6.6 months with investigator’s choice of therapy (fulvestrant alone or everolimus plus exemestane). Studies indicate that targeting CDK4 may cause fewer side effects compared to CDK4/6 inhibitors, which suggests that because the atirmociclib/ fulvestrant combination may be better tolerated, patients may remain progression-free longer.
BCRF researchers Drs. Hope S. Rugo and Shom Goel were involved in the study.
Phase 3 APEX-Breast01 trial
Results from another study, the phase 3 APEX-Breast01 trial, found that rolditamig deuderuxtecan (TQB2102), a novel antibody-drug conjugate (ADC) demonstrated a threefold increase in progression-free survival in patients with HER2-low MBC compared to chemotherapy. Patients on rolditamig deuderuxtecan had 16.4 months of progression-free survival compared to 5.5 months on chemotherapy.
These findings support rolditamig deuderuxtecan as a promising treatment option for patients with HER2-low breast cancer who have not previously received chemotherapy in the metastatic setting. It is currently in late-stage clinical development.
Phase 3 HEALER trial
Researchers from the phase 3 clinical trial HEALER presented promising results on a novel anti-HER2 drug, anbenitamab. It’s a newly developed bispecific antibody which targets two non-overlapping regions of the HER2 protein.
The study’s findings showed that 21 months of follow-up anbenitamab treatment in combination with the chemotherapy drug taxane extended two-year progression-free survival in 59% of patients. This is in comparison to 34% of patients treated with THP, the standard first-line regimen of trastuzumab, pertuzumab, and docetaxel.
Phase 3 HORIZION Breast 06 trial
Results from the phase 3 HORIZON Breast06 trial showed that trastuzumab rezetecan, an experimental antibody-drug concentrate, significantly improved progression-free survival (16.4 months) compared to chemotherapy alone (6.8 months) in patients with HER2-low MBC. The results were not impacted by prior chemotherapy or HR status, and the drug was shown to have a favorable safety profile.
Phase 3PANKU-Breast01 trial
Results from PANKU-Breast01, a phase 3 trial, found that iza-bren (izalontamab brengitecan), another experimental ADC, doubled progression-free survival after 15 months of follow-up in previously treated patients with HR-positive MBC. Progression-free survival was 8.2 months for patients on iza-bren compared to four months with chemotherapy.
Progress in expanding treatment options for triple-negative breast cancer with brain metastases
Phase 3 TROPION Breast02 trial
Treating triple-negative breast cancer (TNBC) has historically been a challenge because it does not express the three main receptors of treatment: estrogen receptor (ER-positive), progesterone receptor (PR-positive), and HER2-positive. And, about a third of patients with TNBC will develop brain metastases, which are also difficult to treat. Together, this makes expanding treatment options for metastatic TNBC with brain metastases an urgent focus.
The phase 3 TROPION Breast02 exploratory study examined whether the recently approved ADC Datroway (Dato-DXd/datopotamab deruxtecan) could improve central nervous system (CNS) progression-free survival—a measure of how long patients lived without brain metastases growing. The results showed that Dato-Dxd had an improved median CNS progression-free survival of 9.5 months compared to 2.6 months with chemotherapy. In an analysis of 24 patients with measurable brain lesions, tumors shrank in about 63% of those on Dato-DXd versus about 38% on chemotherapy.
BCRF researcher Dr. Tiffany A. Traina was involved in the study.
Follow-up studies reported encouraging news
lidERA trial
Previous studies have shown that patients with early-stage HR-positive breast cancer reported fewer side effects with giredestrant, an investigational drug, compared to tamoxifen or aromatase inhibitors.
After a follow-up of more than two and a half years, patient-reported outcomes showed that about 52% of patients were not bothered by side effects when taking giredestrant, compared to 47% taking an aromatase inhibitor (which hinders hormone production) or tamoxifen (an anti-estrogen drug). Additionally, fewer stopped taking giredestrant because of side effects.
BCRF researchers Drs. Aditya Bardia and Sherene Loi were involved in the study.
NATALEE trial
Researchers from the NATALEE trial also reported overall survival rates in early-stage HR-positive, HER2-negative breast cancer. Results showed that after six years of follow-up, patients who received the CDK4/6 inhibitor Kisqali (ribociclib) for three years along with an aromatase inhibitor had a six-year survival rate of 92% compared to 90% with an aromatase inhibitor alone.
Drs. Bardia and Loi were involved in the study.
postMONARCH study
After three years of follow-up, findings from the postMONARCH study demonstrated an improved progression-free survival in patients treated with Verzenio (abemaciclib) plus Faslodex (fulvestrant) compared to Faslodex alone for advanced-stage HR-positive breast cancer. While the overall survival rate was not statistically significant, researchers say the findings support considering this combination for advanced-stage cancers that grow during CDK4/6 inhibitor treatment.
What’s next
Development of newer CDK4 inhibitors and next-generation ADCs and immunotherapies will expand the arsenal of treatments against breast cancer, giving clinicians more options for their patients. The findings presented at ESMO hold great promise, and there is much to be hopeful for. With every new research finding, we are a step closer to more effective tools to stop breast cancer.
