Outcomes among Hispanic metastatic breast cancer patients treated with alpelisib and fulvestrant: Single institution retrospective study.
Authors: Chamorro Yolcar , Mahtani Reshma L. , Monestime Shanada , Dempsey Naomi , Roy Mukesh , Rubens Muni B. , Ahluwalia Manmeet Singh , Sandoval-Leon Ana Cristina 
Published: June 2023

e18836 Background: PIK3CA mutations are found in up to 40% of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancers (MBC). Alpelisib is an oral PIK3CA inhibitor approved in combination with fulvestrant. However, uptake has been limited due to toxicity concerns, most commonly hyperglycemia. Disparities regarding prevalence of diabetes exist among Hispanics (H). We previously reported the incidence and management of hyperglycemia in H MBC patients (pts) treated with alpelisib and fulvestrant at our institution. We now report outcomes and assess treatment patterns of H MBC pts compared to NH MBC pts. Methods: A retrospective chart review was performed to include pts with HR+ HER2- MBC with a documented PIK3CA mutation (detected by ctDNA or tissue) treated with alpelisib in combination with fulvestrant at Miami Cancer Institute from 2019-2022. Pts were identified using pharmacy records and the COTA real-world database (RWD). Cases were excluded where the start date was unclear, or treatment was given for a diagnosis other than breast cancer. Based on available data in the medical record, pts were categorized as H or NH. Descriptive statistical analysis was done using SAS version 9.4 (SAS Inc., Cary, NC). Results: Of 46 pts identified, 34 were included in the final analysis (17 H and 17 NH). The median age was 67 yrs. Median lines of therapy prior to the use of alpelisib and fulvestrant were 3.0 (3 H and 2 NH; p = 0.26). Almost all pts had prior treatment with a CDK4/6 inhibitor (94.1% H vs 100% NH; p = 0.31). Chemotherapy was the most common therapy used after alpelisib discontinuation (41.2% H vs 47.1% NH; p = 0.63). Disease progression was the main reason for discontinuation (64.7% H vs 70.6% NH; p = 0.32) followed by hyperglycemia (23.5% H vs 5.9% NH; p > 0.05). Even though not statistically significant, the median days on treatment were shorter in H compared to NH (131d H vs 217d NH; p = 0.20). A clinical benefit rate of 35.3% was noted in H compared to 58.8% in NH (p = 0.17). Median survival time post receipt of alpelisib was shorter in H compared with NH (15 mo vs 29 mo; p = 0.06). Conclusions: We observed a trend towards shorter time on treatment and median survival time in H pts with HR+ MBC treated with alpelisib and fulvestrant compared to NH pts. This combination was used as second or third line of therapy, with most pts receiving chemotherapy at the time of progression. There was a trend towards less clinical benefit to alpelisib and fulvestrant in H pts vs NH pts. Given hyperglycemia was the second leading cause of treatment discontinuation among H, we hypothesize efforts to optimize glucose control in H will help maximize benefit to therapy and ultimately impact outcomes. Futher studies are warranted to better understand the different outcomes observed in H patients.