e13049 Background: Targeted therapies for actionable genomic changes ( PI3K pathway and ESR1 ) have transformed the treatment (tx) landscape and improved outcomes for HR+/HER2– metastatic breast cancer (mBC) patients (pts). However, their clinical benefits depend on timely genomic testing and appropriate tx selection, both of which remain suboptimal in real-world (RW) practice. This study modeled the population-level clinical impact of improving timely genomic testing and administering appropriately matched tx in U.S. pts with HR+/HER2– mBC, compared with current RW practice. Methods: A Markov-based population model simulated U.S. adults with HR+/HER2– mBC initiating first-line (1L) endocrine therapy (ET), estimating outcomes over 3 years across two tx lines. The base case reflected RW testing (34–62%) and tx uptake (6–29%) by genomic alteration, compared with an optimal scenario assuming 100% timely testing and matched tx. Matched tx was defined as administering ET plus mutation-specific targeted tx when available or ET alone or with non-selected agents for those without actionable mutations for each line. Timely testing was defined as genomic results available before starting a tx line with a targeted option available. Additional scenarios, varying testing and tx rates independently were evaluated. Outcomes included population-level overall survival (OS) across two lines and 1-year progression-free survival (PFS) by line. Model inputs, including PFS, OS, genomic alteration prevalence, and RW testing and tx rates, were derived from published literature. Sensitivity analyses assessed the impact of uncertainty in key inputs. Results: In a modeled population of 44,552 pts, 100% timely genomic testing and tx, vs current RW rates increased receipt of matched tx by 14% in 1L and 68% in 2L. Modeling 100% genomic testing and subsequent administration of appropriately guided tx, compared with RW rates, was associated with a 3.6% absolute improvement in 3-year OS, corresponding to 1,598 fewer OS events, including 578 among 1L patients with PIK3CA-mutated disease. Scenario analyses showed that all but the scenario with no test-to-treat was associated with an improvement in OS vs the base case. In year 1, the comparison of 100% test-to-treat versus base case showed 1,664 progressions or deaths avoided in 1L and 2,353 in 2L. Conclusions: Delays in genomic testing and suboptimal alignment of tx with genomic findings limit the clinical benefit of targeted tx for HR+/HER2– mBC. This model suggests that timely testing and matched therapy, particularly in 1L pts with PIK3CA mutations, may reduce disease progression and mortality. Interpretation should consider modeling limitations, including assumptions about tx adherence and uptake.
Behan et al. (Thu,) studied this question.