Effectiveness of Alpelisib + Fulvestrant Compared with Real-World Standard Treatment Among Patients with HR+, HER2–, PIK3CA-Mutated Breast Cancer

Abstract

Background. The BYLieve trial (NCT03056755) confirmed efficacy and safety of alpelisib with fulvestrant for hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2À), PIK3CA-mutated advanced breast cancer (ABC), after cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with an aromatase inhibitor (AI) as immediate prior therapy. Further analyses were performed to compare efficacy from BYLieve with effectiveness of standard treatment in the real-world setting. Patients and Methods. Patients who progressed on a CDK4/6i plus AI and were treated with alpelisib with fulvestrant in BYLieve were matched with a real-world patient cohort who received standard of care from a deidentified clinico-genomics database (CGDB). Primary and secondary endpoints were to compare progression-free survival (PFS), estimated by the Kaplan-Meier method, and the proportion of patients remaining progression-free at 6 months, respectively, between the 2 cohorts.

Clinical Outcomes With Dabrafenib Plus Trametinib in a Clinical Trial Versus Real-World Standard of Care in Patients With BRAF-Mutated Advanced NSCLC

“…This method reduces confounding bias, while maintaining all patients in a weighted form in the analysis (except for trimmed cohorts), making it a more reasonable method than other propensity score techniques for balancing patient groups with small sample sizes. 33 , 34 …”

New and Emerging Targeted Therapies for Advanced Breast Cancer

“…The PIK3CA mutations induce hyperactivation of the PI3K p110 subunit alpha isoform, thus leading to increased cell growth and proliferation. In the SOLAR-1 and BYLieve clinical trials, the synergistic effect of antitumor activity observed in alpelisib-fulvestrant combination therapy resulted in greater PFS, in contrast to usage of either alpelisib or fulvestrant as monotherapies [23,24]. Because approximately 40% of patients with HR-positive, HER2-negative breast cancer also have the PIK3CA mutation, alpelisib-fulvestrant is an effective therapeutic combination for targeted therapy, especially for cancers with endocrine resistance [22].…”

Type 1 Nuclear Receptor Activity in Breast Cancer: Translating Preclinical Insights to the Clinic

“…Second-line treatment options include fulvestrant, cytotoxic chemotherapy, or anti-oestrogen therapy combined with inhibitors of the mammalian target of rapamycin (mTORi). Additionally, growing evidence supports the use of next-generation oral SERDs ( Table 2 ) and combinatorial strategies with alpha-selective phosphoinositide 3-kinase inhibitors (PI3Ki) in patients harbouring somatic, activating PIK3CA mutations [ 31 , 32 ]. The optimal sequencing of this repertoire of therapeutic strategies, however, remains the subject of ongoing clinical trials such as the SONIA study (ClinicalTrials.gov identifier NCT03425838), and the growing use of commercially available tissue and liquid biopsy-based companion diagnostic panels is leading to a surge in biomarker-driven treatment strategies post-CDK4/6-inhibitor therapy in ER+ metastatic breast cancer.…”