Clinical investigators’ (CIs) practice patterns for patients with hormone receptor-positive metastatic breast cancer (HR+ mBC) harboring PI3K/AKT/PTEN pathway abnormalities (PAPm).

e13091 Background: Therapeutic targeting of PIK3CA mutations in patients with HR+ mBC has been a clinical reality since the 2019 FDA approval of alpelisib. However, the recent approvals of two novel agents, capivasertib (capi) and inavolisib (inavo), have introduced important new considerations for the care of individuals with these and other PAPm. Relevantly, available data on how clinicians are currently approaching the use of these therapies is minimal. Methods: In October 2024, 21 US-based and international CIs completed a case-based survey on PAPm mBC. A modest honorarium was provided. For each case, key clinical considerations including prior therapy, time to disease progression and biomarker profile were varied. Results: For a 65-year-old patient with disease relapse 2 years into adjuvant aromatase inhibitor (AI) therapy, more than two thirds of the CIs would recommend the combination of inavo/palbociclib/fulvestrant if a PIK3CA mutation was present, regardless of whether there was an ESR1 mutation. For a 65-year-old patient with disease progression after 18 months on first-line treatment with an AI and a CDK4/6 inhibitor (CDK4/6i), CIs overwhelmingly recommended capi/fulvestrant for a patient with a PIK3CA mutation (20 of 21) or a PTEN or AKT alteration (21 of 21) with no ESR1 mutation. For patients with both PIK3CA and ESR1 mutations, CIs favored capi/fulvestrant over other approaches. Conclusions: The recent availability of capi and inavo has significantly affected current practice patterns, with the majority of CIs rapidly incorporating these therapies into their treatment algorithms for specific patient types. Future work is needed to explore how other factors (eg, age, comorbidities, HER2-low status) and rapidly emerging clinical trial findings (eg, EMBER-3) affect decision-making. Mutation status Multiple metastases2 y into adjuvant A Disease progression18 moon CDK4/6i + AI PIK3CA+ESR1- IPF: 16/21 (76%)CDK4/6i + F: 5/21 (24%) C + F: 20/21 (95%)Alp + F: 1/21 (5%) PIK3CA+ESR1+ IPF: 15/21 (71%)CDK4/6i + F: 5/21 (24%)Other: 1/21 (5%) C + F: 12/21 (57%)E: 6/21 (28%)Other: 3/21 (15%) AKT or PTEN+ESR1- C + F: 21/21 (100%) A = anastrozole; IPF = inavolisib + palbociclib + fulvestrant; F = fulvestrant; AI = aromatase inhibitor; C = capivasertib; Alp = alpelisib; E = elacestrant.