Abstract P1-18-18: Real-world natural history data among patients with PIK3CA-mutant and PIK3CA-wild-type advanced breast cancer

Autor: Pedram Razavi, Rohan C Parikh, Barbara Acevedo, Abigail Hitchens, Mehnaj Ahmed, Anton Safonov, Emanuela Ferraro, Komal Jhaveri, Michelle Sidel, Stacey Simmons, Mark Robson, Sarat Chandarlapaty, Sanjeev Balu
Rok vydání: 2022
Předmět:
Zdroj: Cancer Research. 82:P1-18
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.sabcs21-p1-18-18
Popis: Background: Oncogenic mutations involving PIK3CA gene (PI3Kα) are observed in over 40% of patients with hormone receptor-positive (HR+) advanced breast cancer (ABC). Clinical efficacy of PI3K inhibition was demonstrated in a recent trial, but data on the natural history of disease by PIK3CA status are limited in ABC. We assessed patient and disease characteristics, treatment patterns, and clinical outcomes among patients with ABC treated at the Memorial Sloan Kettering Cancer Center in the United States, prior to the clinical availability of alpelisib (a PI3Kα inhibitor). Methods: A retrospective medical record review of adult patients diagnosed with HR+ and human epidermal growth factor receptor 2-negative (HER2-) ABC between January 2014 and December 2018 was conducted. Data collection is ongoing and updated results will be presented. Cohorts were determined by eligible patients’ PIK3CA gene status (i.e., mutant or wild-type [WT]), and were frequency matched to have an equal distribution of the year of ABC diagnosis between cohorts. Study measures were descriptively summarized, and the Kaplan-Meier method was used to estimate progression-free survival (PFS) and left truncation-adjusted overall survival (OS), in months. To assess the association of PIK3CA mutation status on OS, a multivariate Cox proportional hazard model adjusted for age, race, stage at diagnosis, menopausal status, visceral disease, bone only disease, and Charlson Comorbidity Index score was computed. Additional adjustment on treatment modalities is planned. Results: Data for 249 PIK3CA-mutant and 143 PIK3CA-WT patients was analyzed. For the mutant cohort, the mean (SD) age was 59.0 (11.2) years, 80.7% were White, 30.9% were diagnosed with de novo ABC, and 54.6% were postmenopausal at initial BC diagnosis. Visceral- and bone only-disease were observed among 41.4% and 21.7% of patients, respectively. Among patients with a single PIK3CA mutation (n=220, 88.4%), the most common mutations were H1047R (37.3%), E545K (20.5%), and E542K (12.7%). Multiple PIK3CA mutations were observed in 29 (11.6%) patients. For the WT cohort, the mean (SD) age was 56.3 (12.1) years, 77.6% were White, 39.9% were diagnosed with de novo ABC, and 45.5% were postmenopausal at initial BC diagnosis. Visceral- and bone-only disease were observed among 51.8% and 16.8% of patients, respectively. Most common 1st-line treatments for ABC were cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) + aromatase inhibitor (AI) (mutant: 38.6%; WT: 40.6%), AI only (mutant: 21.3%; WT:22.4%), CDK4/6i + fulvestrant (mutant: 15.7%; WT: 7.7%), and chemotherapy-based regimens (mutant: 9.6%; WT: 11.2%). Chemotherapy-based regimens were the most common 2nd- (mutant: 25.6%; WT: 21.3%) and 3rd-line (mutant: 41.4%; WT: 33.9%) therapies for both cohorts. Results for PFS and OS are presented in Table 1, and the survival risk was similar for both cohorts (adjusted HR: 1.18, 95% CI: 0.88-1.60). Conclusion: In this preliminary analysis of HR+/HER2- ABC, CDK4/6i-based regimens were the most common 1st-line therapy, and PFS to 1st-3rd line therapies and OS were not statistically significantly different. The recent availability of PI3K inhibitor therapy may improve clinical outcomes among patients with PIK3CA-mutant tumors. Table 1.Progression-free Survival and Overall Survival Among Patients with HR+/HER2- ABC.PIK3CA MutantPIK3CA Wild-typeProgression-free Survival (months)1st line – all patients (n)249143Median (95% CI)12.4 (10.4-15.2)13.5 (10.3-16.0)1st line – CDK4/6i + AI (n)9658Median (95% CI)21.0 (17.0-27.9)19.1 (9.4-28.6)2nd line – all patients (n)211127Median (95% CI)7.3 (6.3-10.4)6.8 (5.4-8.8)2nd line – chemotherapy-based regimens (n)5427Median (95% CI)5.1 (3.7-6.3)5.2 (3.3-6.3)3rd line – all patients (n)186115Median (95% CI)4.5 (3.7-5.4)5.7 (4.7-8.9)3rd line – chemotherapy-based regimens (n)7739Median (95% CI)4.3 (3.0-5.1)4.7 (3.0-7.7)Overall Survival (months)Median (95% CI)47.4 (42.8-52.4)55.5 (44.9-61.9) Citation Format: Pedram Razavi, Rohan C Parikh, Barbara Acevedo, Abigail Hitchens, Mehnaj Ahmed, Anton Safonov, Emanuela Ferraro, Komal Jhaveri, Michelle Sidel, Stacey Simmons, Mark Robson, Sarat Chandarlapaty, Sanjeev Balu. Real-world natural history data among patients with PIK3CA-mutant and PIK3CA-wild-type advanced breast cancer [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 P1-18-18.
Databáze: OpenAIRE
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