Real-World Endocrine-Resistant HR+/HER2- mBC Progresses in ≈8 mo on First-Line CDK4/6i, with 40% PIK3CA Mutations

A Flatiron Health EHR review (2015-2023) captured 7,096 U.S. patients starting first-line therapy for recurrent HR+/HER2- metastatic breast cancer. Among 922 who met INAVO120 endocrine-resistant criteria and still received an ET + CDK4/6 inhibitor (most palbociclib + fulvestrant), PIK3CA mutations were found in 39–41%. Outcomes lagged sharply: real-world median PFS 8.2–8.5 mo, time-to-chemotherapy 16.2–21.7 mo, and OS 27.0–29.7 mo versus 13.0, 33.0, and 36.8 mo in the broader HR+/HER2- cohort. Fast progression ≤6 mo hit 35–38%. **Only ~11% were genotyped before starting therapy, despite 59–61% eventually being tested.**For comparison, pivotal first-line CDK4/6i trials (MONARCH 3) report median PFS ≈29 mo, and adding the PI3Kα degrader inavolisib to palbociclib + fulvestrant extended PFS to 17.2 mo in the INAVO120 study.

https://aacrjournals.org/clincancerres/article/31/12_Supplement/P4-07-27/752629/Abstract-P4-07-27-Real-world-observational-study