A single center experience of PIK3CA and AKT inhibitors in patients with hormone receptor positive metastatic breast cancer.

e13051 Background: Currently there are 3 FDA- approved PI3K/AKT inhibitors: alpelisib, capivasertib and inavolisib. Management of off-tumor on-target side effects of these inhibitors such as hyperglycemia, diarrhea and skin rash remain clinically challenging. This is a single-center retrospective analysis of the efficacy and safety profile of these PI3K/AKT inhibitors. Methods: The retrospective study was conducted through an IRB approved protocol and included patients treated from January 2019 to December 2024. Progression free survival(PFS), dose delay, dose interruption, adverse events, and time to discontinuation (TTD) were collected. Time to treatment discontinuation (TTD) is the time from the start of treatment to when a patient stops taking it. Results: A total of 99 patients(pts) were identified: 55 pts with alpelisib, 33 pts with capivasertib, 1pt with inavolisib, and 10 pts with more than 2 inhibitors. 6.07- Median age was 66 (34-86) Race: White, 75; African-American,10; Asian, 9; other, 2; unknown, 2; declined,1. Median prior lines of therapy was 2 (0-9). 97 pts (except 2) received prior CDK 4/6 inhibitors. Median PFS were: alpelisib 5.8m (CI 3.1- 6.13) and 7.6m (CI 6.07-10.9) for capivasertib treated pts by Kaplan Meier survival analysis. The medial TTD were: 4.2m and 5.9m for alpelisib and capivasertib respectively. The rates of discontinuation other than progression of disease (PD) was 35.4% overall; 32.8% in alpelisib and 16.7% in capivasertib. In the alpelisib group, 9 of 20 pts had dose interruption due to skin rash and diarrhea; 6 pts due to uncontrolled grade 3(5) or 4(1) hyperglycemia. In the capivasertib group, 7 of 10 pts had dose interruption due to rash and diarrhea. 1 pt with inavolisib experienced rash without treatment discontinuation. In addition, 12 pts received alpelisib or capivasertib after everolimus and mPFS of were 5.8m. Among those, 7 pts experienced grade 2 or 3 hyperglycemia. Conclusions: The single center experience of PIK3CA/AKT inhibitors reflected clinical trial result with similar PFS. A lower rate of dose interruptions and lower rate of all grades diarrhea were observed in the real-world data. Prophylactic use of antidiarrhea agents may contribute to the finding although precautions need to be taken due to the retrospective chart review nature of this study. Safety profiles of alpelisib and capivasertib. All grades AEs Phase 3 trials (%) CSMC (%) Alpelisib Hyperglycemia 63.7 46.9 Rash 35.6 43.8 Diarrhea 57.7 40.6 Dose interruption 66.5 31.4 Capivasertib Hyperglycemia 16.3 35.7 Rash 38.0 36.1 Diarrhea 72.7 47.6 Dose Interruption 34.8 28.6