Endocrine Treatment and Targeted Therapy for HR-Positive, HER2-Negative Metastatic Breast Cancer

Publication Date: March 13, 2024
Last Updated: May 3, 2024


Recommendations from 2024 Rapid Recommendation Update

Recommendation 1.1

The Expert Panel recommends multiple lines of endocrine treatment (ET), frequently paired with targeted agents, with choices informed by prior treatments and by routine testing for activating mutations in ESR1, PIK3CA, or AKT1, or inactivation of PTEN (Table 1). Panelists recommend inclusion of CDK4/6 inhibitor therapy with ET in the first line. Second- and third-line therapies reflect targeted options based on tumor genomics. Combining ET with the AKT pathway inhibitor capivasertib is appropriate for tumors harboring PIK3CA or AKT1 mutations or PTEN inactivation while ET combined with the PI3 kinase inhibitor alpelisib is an option for tumors harboring PIK3CA mutations, but not AKT1 mutations. Other options include ET with mTOR inhibitor everolimus irrespective of tumor genomics (Table 1). Monotherapy with the oral selective estrogen receptor degrader (SERD) elacestrant is an option for tumors with ESR1 mutation.

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Qualifying statement for Recommendations 1.1 and 1.2.
Both capivasertib and alpelisb can cause rash and/or diarrhea. Grade 3 or greater AEs included diarrhea (9.3% capivasertib vs 6.7% alpelisib), rash (12.1% capivasertib vs 9.9% alpelisib), and hyperglycemia (2.3% capivasertib vs 36.6% alpelisib). Clinicians may mitigate symptoms with antihistamines, anti-diarrheal agents, or other supportive measures. Most patients with estrogen receptor (ER)-positive, HER2-negative breast cancers will be candidates for multiple lines of ET and/or targeted agents prior to chemotherapy or antibody-drug conjugate therapy. While newer agents have been added to the armamentarium, there remain few studies on the optimal timing or sequence of treatments, comparisons of targeted agents within a class, or studies that compare one class of agents against another. Such trials are an important clinical priority, as are studies to mitigate side effects of these agents.




Endocrine Treatment and Targeted Therapy for HR-Positive, HER2-Negative Metastatic Breast Cancer

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