Alpelisib Plus Endocrine Therapy Yields Similar PFS Benefits in Subgroup Analysis of PIK3CA-Mutated, HR-Positive / HER2-Negative Breast Cancer

The combination of alpelisib (Piqray) plus endocrine therapy with a clinical benefit across all subgroups of patients with hormone receptor (HR) –positive, HER2-negative advanced breast cancer PIK3CA Mutations, according to data from a subgroup analysis of the Phase 2 BYLieve trial (NCT03056755) presented in a poster at the European Society for Medical Oncology Breast Cancer Congress 2022.¹

Across 3 cohorts, progression-free survival (PFS) ranged from 5.1 to 16.6 months in subgroups classified by menopausal status, bone-only lesions, and visceral disease. Patients in cohorts A and C received alpelisib plus fulvestrant (Faslodex), and patients in cohort B were administered alpelisib plus letrozole (Femara).

In cohort A, premenopausal patients (n = 20) had a median PFS of 5.6 months (95% CI, 3.4-11.1), compared with 8.1 months (95% CI, 5.6-8.6) in postmenopausal patients (n = 101). Patients with bone-only lesions (n ​​= 22) achieved a median PFS of 16.6 months (95% CI, 11.1 – not evaluable) [NE]), vs patients with bone-only lesions (n ​​= 99) in 5.6 months (95% CI, 5.3–8.2). In patients with visceral disease (n = 82), the median PFS was 5.6 months (95% CI, 4.8-8.2), compared with 12.0 months (95% CI, 7.0-18.2) in patients with visceral disease (n = 39). .

In cohort C, premenopausal patients (n = 6) had a median PFS of 5.1 months (95% CI, 0.9-NE), compared with 5.7 months (95% CI, 3.7-7.2) in postmenopausal patients (n = 109). Patients with bone-only lesions (n ​​= 11) achieved a median PFS of 11.0 months (95% CI, 2.8-NE), vs 5.5 months (95% CI, 3.7-6.2) with patients without bone-only lesions (n ​​= 11). 104). In patients with visceral disease (n = 88), the median PFS was 5.5 months (95% CI, 3.6-6.2), compared with 10.8 months (95% CI, 5.1-14.8) in patients with visceral disease (n = 27). .

In cohort C, premenopausal patients (n = 16) had a median PFS of 6.9 months (95% CI, 2.8-11.7), compared with 5.6 months (95% CI, 5.4-7.4) in postmenopausal patients (n = 98). Patients with bone-only lesions (n ​​= 14) achieved a median PFS of 5.5 months (95% CI, 2.8-10.2), vs 5.6 months (95% CI, 5.4-8.1) with patients without bone-only lesions (n ​​= 14). 101). In patients with visceral disease (n = 85), the median PFS was 5.6 months (95% CI, 5.4-8.1), compared with 6.4 months (95% CI, 4.8-8.4) in patients with visceral disease (n = 30). .

“This analysis further confirms the clinical relevance of targeting the PIK3CA The clinical benefit given to the driver mutation was with the patients in the observation PIK3CAAlpelisib plus endocrine therapy with patients with -mutated tumors has diverse demographic and disease characteristics and varied prior treatments, ”lead study author Fatima Cardoso, MD, director of the Breast Unit of the Champalimaud Clinical Center in Lisbon, Portugal, wrote.

Approximately 40% of patients have HR-positive / HER2-negative advanced breast cancer a PIK3CA driver mutation.² The Presence of PIK3CA Mutations are associated with a poor prognosis and can contribute to endocrine therapy resistance.

In May 2019, the FDA approved alpelisib plus fulvestrant HR-positive, HER2-negative, with postmenopausal patients as a treatment. PIK3CA-Mutated, an endocrine-based regimen on or after progression following advanced or metastatic breast cancer.³

The BYLieve trial assessed the utility of combining alpelisib with additional endocrine therapies in patients with HR-positive / HER2-negative. PIK3CA-Mutated aggressive breast cancer who progresses on a CDK4 / 6 inhibitor or an aromatase inhibitor, a CDK4 / 6 inhibitor plus a fulvestrant, or an aromatase inhibitor followed by chemotherapy or endocrine therapy as immediate prior treatment, across 3 cohorts. These subgroup analyzes of BYLieve aimed to evaluate patients based on menopausal status, bone-only lesion status, and visceral disease status.

All patients were enrolled in a trial that required pretreated HR-positive, HER2-negative advanced breast cancer harboring a. PIK3CA mutation in tumor tissue or blood. Prior lines of treatment may include a CDK4 / 6 inhibitor plus endocrine therapy, systemic chemotherapy, or endocrine therapy alone. Moreover, patients required ECOG performance status no greater than 2, plus measurable disease per RECIST v1.1 criteria, or at least 1 predominantly lytic bone lesion.

Cohort A featured patients who received a CDK4 / 6 inhibitor plus an aromatase inhibitor immediately prior to treatment (n = 127). This cohort received 300 mg of oral alpelisib per day plus 500 mg of fulvestrant on day 1 and day 15 of the first cycle, followed by day 1 only in cycles. Cohort B included patients who received a CDK4 / 6 inhibitor plus fulvestrant as an immediate prior treatment (n = 126). These patients received 300 mg of oral alpelisib per day, plus 2.5 mg of oral letrozole per day. Cohort C evaluated patients with an aromatase inhibitor whose disease progressed or after treatment and then received chemotherapy or endocrine therapy as immediate prior treatment (n = 126). These patients received the same dosing of alpelisib and fulvestrant as cohort A.

The primary end point of the trial was a cohort of patients living with progressive disease at 6 months per RECIST v1.1 criteria in each cohort. Previous findings showed that the primary end point was reached in all 3 cohorts. Secondary end points included PFS, secondary PFS, overall response rate, clinical benefit rate, duration of response, overall survival and safety. Biomarker analysis served as an exploratory end point.

Baseline characteristics were well-balanced among patients with cohorts A, B, and C. A majority of patients received 1 cohort of 1 prior line of therapy, had stage IV disease, and had an ECOG performance status of 0. Most patients. Premenopausal under age was 46 years (range, 32-56) and those who were postmenopausal were 61 years of age (range, 31-84).

References

1. Cardoso F, Juric D, Lerebours F, et al. PIK3CA ‐ mutated, hormone receptor ‐ positive (HR +), human epidermal growth factor receptor 2 ‐ negative (HER2–) advanced breast cancer (ABC): patients with alpelisib (ALP) + endocrine therapy (ET): BYLieve study from subgroup analyses . Presented at: 2022 ESMO Breast Cancer Congress; May 3-5, 2022; Berlin, Germany. Poster 175P.
2. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumors. Nature. 2012; 490 (7418): 61-70. doi: 10.1038 / nature11412
3. FDA approves metastatic breast cancer for alpelisib. News release. FDA. Accessed May 24, 2019. Accessed May 6, 2022. https://bit.ly/3vNjWfJ