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Opinion|Videos|February 18, 2025

Genotype-Directed Therapies for HR+/HER2– Advanced Breast Cancer

Panelists discuss genotype-directed treatment options for advanced HR+/HER2– disease, including PI3K/AKT/mTOR inhibitors and antibody-drug conjugates (ADCs), their use based on recent data, impressions of these regimens, and how the recent first-line approval of inavolisib in combination with palbociclib and fulvestrant for PI3K-mutated HR+/HER2– metastatic breast cancer may change the treatment paradigm.

Episodes in this series

EP. 1 Diagnosis and Risk Stratification for Early-Stage HR+/HER2- Breast Cancer

EP. 1 Diagnosis and Risk Stratification for Early-Stage HR+/HER2- Breast Cancer

EP. 2 CDK4/6 Inhibitors for HR+/HER2- Early Breast Cancer

EP. 2 CDK4/6 Inhibitors for HR+/HER2- Early Breast Cancer

EP. 3 Current Practices for Targeted Therapies and Molecular Testing for HR+/HER2- Metastatic Breast Cancer

EP. 3 Current Practices for Targeted Therapies and Molecular Testing for HR+/HER2- Metastatic Breast Cancer

EP. 4 Exploring 1L and 2L CDK4/6 Inhibitors + Endocrine Therapies

EP. 4 Exploring 1L and 2L CDK4/6 Inhibitors + Endocrine Therapies

EP. 5 Clinical Perspectives: Use of CDK4/6i After CDK4/6i

EP. 5 Clinical Perspectives: Use of CDK4/6i After CDK4/6i

EP. 6 The Current Treatment Landscape of Oral SERDs in Metastatic Breast Cancer

EP. 6 The Current Treatment Landscape of Oral SERDs in Metastatic Breast Cancer

EP. 7 Clinical Findings of Elacestrant, an Oral SERD for ER+/HER2– Metastatic Breast Cancer

EP. 7 Clinical Findings of Elacestrant, an Oral SERD for ER+/HER2– Metastatic Breast Cancer

EP. 8 Emerging Data of Additional SERDs in Metastatic Breast Cancer

EP. 8 Emerging Data of Additional SERDs in Metastatic Breast Cancer

EP. 9 CDK4/6 Inhibitors Plus Novel Agents for ER+/HER2–Advanced or mBC

EP. 9 CDK4/6 Inhibitors Plus Novel Agents for ER+/HER2–Advanced or mBC

EP. 10 Toxicities and Treatment Selection of Endocrine-Based Therapies in HR+/HER2– Breast Cancer

EP. 10 Toxicities and Treatment Selection of Endocrine-Based Therapies in HR+/HER2– Breast Cancer

EP. 11 Genotype-Directed Therapies for HR+/HER2– Advanced Breast Cancer

EP. 11 Genotype-Directed Therapies for HR+/HER2– Advanced Breast Cancer

EP. 12 Exploring Data of PI3K/AKT/mTOR Inhibitors in HER2– mBC

EP. 12 Exploring Data of PI3K/AKT/mTOR Inhibitors in HER2– mBC

EP. 13 Clinical Developments of Antibody-Drug Conjugates (ADCs) in HR+/HER2– mBC

EP. 13 Clinical Developments of Antibody-Drug Conjugates (ADCs) in HR+/HER2– mBC

EP. 14 ADCs: Recent Data of Dato-DXd from TROPION-Breast01

EP. 14 ADCs: Recent Data of Dato-DXd from TROPION-Breast01

EP. 15 Impact of ADC Toxicities and Clinical Decision-Making for mBC

EP. 15 Impact of ADC Toxicities and Clinical Decision-Making for mBC

EP. 16 Continued Advances and Treatment Sequencing for HR+/HER2– Breast Cancer

EP. 16 Continued Advances and Treatment Sequencing for HR+/HER2– Breast Cancer

DISCLAIMER: In the Phase 3 INAVO-120 Study evaluating inavolisib+palbociclib+fulvestrant, the correct PFS data is 15 months vs. 7.3 months, not 24 vs. 15 months as stated; 2) Time to chemotherapy data was not available at primary analysis; 3) The safety profile characterization was incomplete - the treatment showed a low discontinuation rate of only 6% due to adverse events, with grade 3+4 AEs (specific to Rash & Nausea) were 0%.

Video content above is prompted by the following:

Dr. Bardia to Dr. Chan: What are the more genotype-directed options for advanced HR+/HER2–- disease (PI3K/AKT/mTOR inhibitors, ADCs, etc.) ?

How, and for what patient populations, are these being used based on the most recent data? What are your impressions of each of these regimens?

Inavolisib – How might the recent first-line inavolisib approval change the treatment paradigm? (approved in combination with palbociclib and fulvestrant for patients withPI3K-mutated, HR+, HER2–- la /metastatic breast cancer mBC that who progress on or relapse within 12 months after completing adjuvant endocrine therapy)change the treatment paradigm?

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