Poster Spotlight Session 17: Biomarkers of Response and/or Resistance to Endocrine Based Therapies: Implications for Treatment Approaches
Friday, December 8 • 7:00 a.m. – 8:00 a.m. • Hemisfair Ballroom 1-2
Presentation: Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant HR-positive/HER2-negative advanced breast cancer: exploratory analysis of PFS by PIK3CA/AKT1/PTEN alteration from the Phase 3 CAPItello-291 trial
Sacha Howell, PhD, FRCP
The University of Manchester,
Manchester, England
What is your presentation about?
In the CAPItello-291 Phase 3 trial (NCT04305496) in patients with HR-positive/HER2-negative advanced breast cancer who had relapse or disease progression during or after aromatase inhibitor treatment with or without prior CDK4/6 inhibitor therapy, the addition of capivasertib (a potent, selective inhibitor of all three AKT isoforms) to fulvestrant significantly improved the dual primary endpoints of PFS in the overall population and in patients with PIK3CA/AKT1/PTEN–altered tumors.
Our presentation reports on an exploratory analysis of progression-free survival results from CAPItello-291 trial by PIK3CA, AKT1 and PTEN alteration along with an ad hoc pooled analysis of data gathered in a Chinese extension to the original study.
What makes this topic important in 2023?
Capivasertib plus fulvestrant has the potential to be a future treatment option for patients with HR-positive/HER2-negative advanced breast cancer who have progressed on, or after, an endocrine-based regimen. These data provide further information on progression-free survival separately for each of the PIK3CA/AKT1/PTEN–altered tumors.
Presentation: Clinical and Genomic Features of ER-Positive/HER2-negative Metastatic Breast Cancer in AURORA Molecular Screening Initiative (BIG 14-01): Mechanisms of Endocrine Therapy Resistance and Implications for Adjuvant Approaches
Angel Guerrero-Zotano, MD, PhD
Fundación Instituto Valenciano de Oncología (FIVO), Valencia, Spain
GEICAM Spanish Breast Cancer Group, San Sebastian, Spain
What is your presentation about?
This study is part of the AURORA-EU program and focuses on 628 ER+/HER2- metastatic breast cancer patients, exploring genomic differences between adjuvant endocrine therapy (ET)-sensitive and -resistant relapses. We found that ET-resistant tumors show greater differences from their primaries than ET-sensitive or de-novo tumors, regardless of type of adjuvant ET. Nine percent of luminal tumors shift to non-luminal subtypes in metastases, with poor response to CDK4/6 inhibitors and worse overall survival. Most importantly we found a high prevalence (around 22%) of acquired ESR1 mutations observed before first-line therapy, especially in tumors exposed to adjuvant AI or with primary/secondary ET resistance and these mutations were independently associated with worse overall survival.
What makes this topic important in 2023?
The AURORA study, which uniquely investigates paired primary-metastatic tumors, in a large ER+ MBC cohort provides insights into genomic alterations acquired during adjuvant anti-cancer therapy. We discovered a higher prevalence of ESR1 mutations before first-line therapy than previously reported, particularly associated with AI treatment and adjuvant ET resistance. These mutations were associated with worse OS. The findings suggest that ESR1 mutations may contribute to relapse in aggressive ER+/HER2- early breast cancer, emphasizing the need for enhanced adjuvant endocrine therapy strategies to prevent the emergence of these mutations. From a clinical perspective, considering ESR1 mutation status is crucial when making treatment decisions and assessing prognosis for ER+/HER2- metastatic breast cancer patients initiating first-line treatment.