Abstract P5-13-16: A real-world assessment of PIK3CA testing and alpelisib treatment patterns among metastatic breast cancer patients in a community oncology setting
Authors: O'Shaughnessy Joyce , Paulson Steven , Brisbin Lorraine , Lindsey James , Williford Anna , Lisi Monica , Parikh Rohan C. , Simmons Stacey , Balu Sanjeev 
Published: March 2022

Abstract
Background: Alpelisib (PIQRAY®) in combination with fulvestrant was approved by the US- FDA in May of 2019 for patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) PIK3CA mutant advanced or metastatic breast cancer (aBC or mBC) following progression on aromatase inhibitors. Prior to the US-FDA approval of alpelisib, routine molecular profile testing for this patient population was not supported by NCCN guidelines. Thus, data on the natural history of HR+/HER2- mBC patients, particularly in terms of biomarker testing and treatment patterns in a real-world patient setting, are limited. To understand integration of alpelisib into clinical practice for this patient population, this retrospective non-interventional study assessed biomarker testing, treatment patterns, and patient characteristics for patients at Texas Oncology (TxO) from 2015 to 2020.Methods: The study index date was defined as the first date of a new diagnosis of advanced BC (de novo or recurred mBC) between January 2015 and June 2020 with a minimum follow-up opportunity of 6 months follow-up. Treatment patterns were assessed until December 2020, allowing assessment of alpelisib real-world utilization post the US-FDA approval. Databases curated included the EMR (iKM), the TxO Precision Medicine (PM) Molecular databases. Information mined included total number of mBC patients, HR and HER2 status, and the presence and classification of PIK3CA mutations. Treatment patterns were also examined. Results: Study cohort consisted of 1093 patients for whom PIK3CA, HR, HER2 status and systemic treatment were known. Of these, 768 (70%) were HR+/HER2-, 220 (20%) were HR-/Her2HER2-, 73 (7%) were HR+/Her2HER2+ and 32 (3%) were HR-/Her2HER2+. Among all subtypes, 410 (38%) were PIK3CA mutant, and within HR+/HER2- cohort, 333 (43%) were PIK3CA mutant. Of the 105 patients treated with alpelisib, 102 (97%) were treated after drug approval, and the remaining 3 patients (3%) received alpelisib via compassionate use program. Within the HR+/HER2-/PIK3CA mutant patient cohort (n=333), 97 (29%) were treated with alpelisib. The most frequent alpelisib-containing regimen is alpelisib+fulvestrant, given to 84 (87%) of patients. It is most frequently given as a second- (n=28, 29%), third- (n=16, 16%) and fourth-line (n=16, 16%) lines of therapy. Out of 97 patients, 69 (71%) were treated previously with a cyclin-dependent kinase 4/6 inhibitor. The median duration of alpelisib therapy was 4.6 months. As of December 30, 2020, 34 of the 97 patients had treatment with alpelisib ongoing, 24 expired, 14 were referred to hospice,18 completed last recorded line of therapy prior to study end date, and 7 patients progressed to the next line of therapy. There was no noteworthy difference in patients treated vs. not treated with alpelisib with respect to age (mean 61.5 vs. 59.3 yrs.) or performance status (Karnofsky) (29% vs. 25% at 100%, 42% vs. 49% at 90% respectively). In PIK3CA mutant cancers, the most frequent PIK3CA mutations were H1047R, E545K, E542K, N345K and H1047L, and 43 (10%) had 2 or more mutations. Patient outcomes including the median progression free survival was also determined for this cohort and will be reported. Conclusions: This retrospective study demonstrates that 38% of mBC patients’ cancers across all sub-types harbored a PIK3CA mutation where multiple testing platforms were utilized in the community setting. Approximately 30% of patients with HR+/HER2-/PIK3CA mutant status did receive alpelisib. Co-morbidities and other clinically relevant factors between PIK3CA mutant patients who did and did not receive alpelisib, such as those on oral diabetes medication, insulin or had elevated HgbA1c, should be studied further.
Citation Format: Joyce O'Shaughnessy, MD, Steven Paulson, MD, Lorraine Brisbin, M.S, James Lindsey, Anna Williford, Ph.D, Monica Lisi, Rohan C. Parikh, Ph.D, Stacey Simmons, MD and Sanjeev Balu, Ph.D. A real-world assessment of PIK3CA testing and alpelisib treatment patterns among metastatic breast cancer patients in a community oncology setting [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 P5-13-16.