1073 Background: Current literature on the treatment patterns and economic burden among newly diagnosed patients (pts) with HR+/HER2- metastatic breast cancer (mBC) is outdated and may not adequately capture the rapidly evolving treatment landscape. This study addresses this gap by providing a contemporary and comprehensive summary of real-world treatment patterns, healthcare resource utilization (HRU) and cost of care among HR+/HER2- mBC pts, through their first 3 lines of treatment (LOT) following metastatic diagnosis (met dx). Methods: We retrospectively identified adult women with newly diagnosed HR+/HER2- mBC between 10/01/2016 - 06/30/2022 from the IQVIA PharMetrics Plus database. Pts were required to have≥ 6 months of follow up post met dx. The study classified pts hierarchically into mutually exclusive treatment categories across 3 LOTs following met dx: endocrine therapy only (ET), CDK4/6 inhibitor-based therapy (CDKi), alpelisib-based therapy (ALP), mTOR inhibitor-based therapy (mTOR), PARP inhibitor (PARPi), or chemotherapy (CT). Categories with < 30 pts in each line or those with overlapping targeted treatments were grouped into “Others'' (OTH). Baseline characteristics were assessed in the 12 months prior to met dx. HRU and costs of care (in 2022 USD) were measured during the follow-up period and reported in per patient per month (PPPM). Results: The study included 2,449 pts, with 64.6%, 10.5%, 22.8%, 2.1% pts receiving CDKi, CT, ET and OTH in 1LOT, respectively. In 2LOT (n=1,164), 41% of pts received CDKi, 24% CT, 20% ET, 9% mTOR, 4% ALP and 3% OTH. In 3LOT (n=479), 44% of pts received CT, 21% CDKi, 15% ET, 9% mTOR, 6% ALP and 4% OTH. The median treatment duration in 1LOT was longest for pts receiving CDKi (23.5 months) compared to 17.1 months for ET. The PPPM total costs were $15,396, $16,955 and $17,853 in 1, 2 and 3LOT. In 1LOT, CDKi pts had the highest PPPM costs [Table]. In the 2/3 LOT, ALP-treated pts incurred the highest costs followed by CDKi in 2LOT and mTOR-treated pts in 3LOT (Table). CT and ALP had the highest ER visits in 2 (0.18 and 0.13) and 3 LOT (0.20 and 0.27). Conclusions: The majority of patients received CDKi treatment as their 1LOT with a more fragmented treatment landscape in the 2/3LOTs. The incorporation of agents targeting the PI3K pathway (ALP and mTOR) remained low in the 2/3LOTs. Costs associated with the same targeted treatment increased when used in later lines of therapy. Early optimization of targeted therapy and a focus on adverse event management may be associated with economic benefits. [Table: see text]