Incidence and outcomes among patients with HR+/HER2- metastatic breast cancer (mBC) with co-occurring ESR1 and PIK3CA mutations detected by ctDNA and treated with alpelisib: A retrospective review.

person Naomi Dempsey Miami Cancer Institute, Baptist Health South Florida, Miami, FL info_outline Naomi Dempsey, Yolcar Chamorro, Dana Tolman, Ana Cristina Sandoval-Leon, Leylah Drusbosky, Courtney Lewis, Manmeet Singh Ahluwalia, Reshma L. Mahtani

Authors person Naomi Dempsey Miami Cancer Institute, Baptist Health South Florida, Miami, FL info_outline Naomi Dempsey, Yolcar Chamorro, Dana Tolman, Ana Cristina Sandoval-Leon, Leylah Drusbosky, Courtney Lewis, Manmeet Singh Ahluwalia, Reshma L. Mahtani Organizations Miami Cancer Institute, Baptist Health South Florida, Miami, FL, Miami Cancer Institute, Plantation, FL, Guardant Health, Inc., Palo Alto, CA, Guardant Health, Redwood City, CA, Miami Cancer Institute, Baptist Health South Florida, Plantation, FL Abstract Disclosures Research Funding No funding received None. Background: ESR1 and PIK3CA mutations inform the use of targeted agents such as alpelisib and elacestrant in patients (pts) with HR+/HER2- metastatic breast cancer (mBC) following progression. Each of these mutations predict a worse prognosis and shorter response to endocrine therapy (ET). The prevalence of PIK3CA and ESR1 mutations detected via cell-free tumor DNA (ctDNA) in mBC is about 35% and 33%, respectively, and the co-occurrence rate ranges from 10-15%. Here, we evaluate the incidence and outcomes of pts with mBC HR+/HER2- harboring co-occurring ESR1 and PIK3CA mutations as detected by ctDNA in a real-world tertiary care center with a predominantly Hispanic patient population. Methods: We analyzed pts with HR+/HER2- mBC with ctDNA testing (Guardant360) between Jan 1, 2020 and Jan 31, 2023 at Miami Cancer Institute. We determined the rate of co-occurrence of activating PIK3CA and ESR1 mutations (co-mutation group). In these pts, demographics, disease characteristics, response to alpelisib + ET, and overall survival (OS) after diagnosis of mBC were collected. For comparison, we analyzed pts with PIK3CA mutations but no ESR1 mutation detected who had received alpelisib + ET ( PIK3CA only group). Results: 372 patients with a diagnosis of mBC who underwent ctDNA testing during the study period, 80 (21.5%) had at least one activating PIK3CA mutation, and 37 (9.95%) had a co-occurring ESR1 mutation. Median age was 70 vs 69 years in the PIK3CA only group compared to the co-mutation group, with 82% vs 92% being post-menopausal, respectively. In the PIK3CA only group, 36.4% were of Hispanic ethnicity, while 70.3% of those in the co-mutation group were Hispanic. Most pts received prior CDK4/6 inhibitor (91% in PIK3CA only group vs 97% with co-mutation). 16 (43.2%) of the 37 patients in the co-mutation group were treated with alpelisib + ET after detection of the co-occurring mutation via ctDNA, and outcomes were compared to the PIK3CA only group. Pts in the PIK3CA only group were treated with alpelisib + ET for a median of 7.23 months vs 4.24 months in the co-mutation group (p=0.6023). Reason for discontinuation, most commonly progressive disease (63.6% in PIK3CA only vs 62.5% in co-mutation) was similar between groups. A partial response or better was seen in 30% of the PIK3CA only group vs 20% of the co-mutation group. OS was 138 months for PIK3CA only vs 98 months for the co-mutation group (p=0.96). Conclusions: The incidence of co- PIK3CA and ESR1 mutations in this predominantly Hispanic patient population was consistent with previously reported literature. We identified a trend towards worse OS and shorter duration on treatment with alpelisib + ET in the co-mutation group as compared to the PIK3CA alone group. Further studies are needed to understand the optimal sequencing of therapy in pts with co-mutation in ESR1 and PIK3CA .