Editor's Note: The 14th European Breast Cancer Conference (EBCC-14) was recently held in Milan, Italy, focusing on new clinical and translational research data in the multidisciplinary management of breast cancer. Oncology Frontier had the pleasure of interviewing the National Chair of this conference, Associate Professor Giuseppe Curigliano from the University of Milan, to discuss the highlights of this event.Oncology Frontier: Could you share some of the most exciting data or highlights from EBCC-14?
Professor Giuseppe Curigliano: I believe there are two particularly important abstracts at this conference. One discusses the impact of physical activity on the quality of life and outcomes of patients with metastatic breast cancer (PREFERABLE-EFFECT), and the other covers the use of immune checkpoint inhibitors in HR+/HER2- early-stage breast cancer (KEYNOTE-756). Engaging in physical activity during adjuvant treatment is the best way to prevent cancer recurrence and improve quality of life. The latest data from the KEYNOTE-756 study shows that adding pembrolizumab to neoadjuvant chemotherapy for locally advanced and high-risk HR+/HER2- breast cancer patients improves the pathological complete response (pCR) rate, particularly in patients with high CPS scores and high TILs. I believe this is a promising treatment strategy, but we need to observe the event-free survival (EFS) data in the future.
Oncology Frontier: What role do you think CDK4/6 inhibitors play in the treatment of HR+ breast cancer patients, and are you optimistic about their future development prospects?
Professor Giuseppe Curigliano: CDK4/6 inhibitors such as ribociclib, abemaciclib, and palbociclib have become the standard of care in the first-line treatment for HR+/HER2- metastatic breast cancer patients. These drugs have shown improvement in median progression-free survival (PFS) in first-line treatments, with some studies also showing overall survival (OS) benefits. We also know that abemaciclib and ribociclib have been tested in early HR+/HER2- breast cancer (monarchE and NATALEE studies). We now have five-year follow-up data for abemaciclib in high-risk HR+/HER2- populations from the monarchE study, showing improvements in five-year invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS). Abemaciclib has been approved in Europe and the United States for adjuvant treatment in high-risk HR+/HER2- breast cancer patients. Data from the NATALEE study has also been presented, showing that ribociclib seems to improve IDFS and DRFS with a shorter follow-up of three years. The NATALEE study included a different patient population, incorporating some intermediate-risk patients.
Oncology Frontier: In the debate on “HER2-low,” your opinion is “Trastuzumab deruxtecan for all HER2-negative metastatic breast cancer patients.” Please tell us the relevant reasons.
Professor Giuseppe Curigliano: The DESTINY-Breast 04 study data shows that trastuzumab deruxtecan (T-DXd) significantly improves median PFS (10.1 months) and OS in patients with HER2 1+/2+ but FISH-negative (HER2-low). We are awaiting the DESTINY-Breast 06 study data, which, if positive, will extend this treatment strategy to HER2 (0) patients. I believe T-DXd should be the preferred treatment for all HER2-low patients. Of course, we need to see the DESTINY-Breast 06 study data. If it shows different clinical benefits in HER2 (0) patients, we will decide whether to prefer T-DXd or standard chemotherapy based on the safety profile. However, I expect T-DXd to be superior to chemotherapy.
Oncology Frontier: The emergence of targeted therapy has brought better survival benefits for HR+/HER2- advanced breast cancer. Currently, ADC drug development is booming. What targeted therapy drugs (including ADC) do you think will appear in the treatment field of HR+/HER2- advanced breast cancer patients in the future?
Professor Giuseppe Curigliano: In first-line treatment, endocrine therapy combined with CDK4/6 inhibitors is the mainstay. In the second line, we have a biomarker-driven approach. For patients with PI3K, AKT, or PTEN mutations, based on CAPItello-291 data, we can use capivasertib combined with fulvestrant, achieving a median PFS of 7.3 months, independent of AKT alterations. Based on the SOLAR-1 and BYLieve studies, we may also use alpelisib, with a median PFS of 7 months in the post-CDK4/6 setting. If patients have ESR1 mutations, we may consider elacestrant, with a median PFS close to 9 months. For patients with a longer exposure to first-line CDK4/6 inhibitors and BRCA mutations, PARP inhibitors can be considered. We are awaiting the DESTINY-Breast 06 study data to see if T-DXd can be incorporated into the second-line treatment for HER2-low and HER2 (0) populations. In the future, I foresee first-line treatment with endocrine therapy plus CDK4/6 inhibitors, second-line biomarker-driven treatments for endocrine-sensitive populations, and ADC treatments from the third line onward. Currently, T-DXd followed by sacituzumab govitecan (SG, anti-TROP-2) in HER2-low patients is the approach. SG should be the first option for HER2 (0) patients. Future options may include datopotamab deruxtecan (dato-DXd) for HER2 (0) and TROP-2 positive patients. The main question for the future will be how to better sequence ADC treatments. Clinical trials with median PFS as a primary endpoint may be needed to address this.
