Abstract P5-13-19: Sarcopenia and skeletal muscle density as predictors of toxicity in patients with metastatic breast cancer receiving alpelisib
Authors: Raphael Ari , Kessner Rivka , Raphael Rebeka , Sonnenblick Amir , Shachar Shlomit Strulov 
Published: March 2022

Background: Poor body composition metrics (BCM) are associated with inferior cancer outcomes. Alpelisib, a PIK3CA inhibitor, is increasingly used in approximately 40% of hormone receptor positive HER2 negative (luminal) metastatic breast (HR-MBC) patients who carry a somatic mutation in the PIK3CA gene. In the SOLAR-1, the clinical trial that led to FDA approval, serious adverse reactions occurred in 35% patients who were treated with Alpelisib and severe hyperglycemia was reported in 65% of the patients. Alpelisib is given at a fixed dose (300 mg daily) regardless of variables such as high adiposity or low muscle mass also called sarcopenia. In this study we investigated the association of BCM with toxicity and response to Alpelisib. Methods: Eligible HR-MBC patients treated with Alpelisib at Tel Aviv Sourasky Medical Center were identified. Toxicity grading, dose reduction, treatment discontinuation and hospitalizations were recorded. Using computerized tomography (CT) images taken for the evaluation of disease burden, skeletal muscle area (SMA), and skeletal muscle density (SMD) were measured at the third lumbar (L3) vertebrae. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2) &lt;41 (Martin, JCO 2012). Low skeletal muscle density (SMD) was defined as &lt; 37.8 Hounsfield Units (HU). Fisher exact tests, t tests, the Kaplan-Meier method, and Cox regression modeling were used. Results: All together Seventeen HR-MBC with PIK3CA mutation treated with Alpelisib met the study requirements. Median age was 63 (range 37-82). Of them 71% were sarcopenic. Any grade toxicity appeared in 83% of the sarcopenic patients versus 20% is the non-sarcopenic (P=0.0276). Both toxicity-related hospitalization and grade 3-4 toxicities and were found in 25% of the sarcopenic vs 0% in the non-sarcopenic. Severe adverse events - defined as grade 3-4 toxicities, hospitalization and dose reductions appeared in 66.6% of the sarcopenic vs 40% of the non-sarcopenic (P=NS). Low SMD appeared in 76% of the cohort. In the low SMD group 69% experienced grade 3-4 toxicity vs 25% in high SMD (P=NS). Hyperglycemia in all grades appeared in all the sarcopenic patients and 80% of the non-sarcopenic. Time to treatment failure (time to progression or toxicity) was numerically shorter in the sarcopenic group vs non-sarcopenic group (82 days vs 114 days respectively). Conclusion: AEs percentage was significantly higher in patients with sarcopenia. These AEs were seen more often in the early cycles. TTF on Alpelisib was shorter in the sarcopenic and low SMD groups. We assume that it was not statistically significant probably due to the low number of patients. Hence, we suggest a novel tool including two parameters (sarcopenia and SMD) for prediction of treatment toxicity which may serve for better treatment decision in the course of the disease in HR-MBC. As Aplelisib is reimbursed in Israel since 2021, we expect additional patients in our cohort and at SABCS 2021, we will extend our cohort and analysis.

Data and statisticsSarcopenicNon-SarcopenicP-valueLow SMDHigh SMDP-valueHyperglicemia all grades100%80%0.294192.31%100%0.0475Hyperglicemia grade 3-433.33%40%138.46%25%1AEs all grades83.33%20%0.027669.23%50%0.584AEs grade 3-425%00.514715.38%25%1SAE including G3-4 AEs + hospitalization + dose reductions66.67%40%0.592869.23%25%0.25TTF (days)82114187991

Citation Format: Ari Raphael, Rivka Kessner, Rebeka Raphael, Amir Sonnenblick, Shlomit Strulov Shachar. Sarcopenia and skeletal muscle density as predictors of toxicity in patients with metastatic breast cancer receiving alpelisib [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-19.