ALP Plus Fulvestrant Delivers Solid Results for PIK3CA-Mutated, HR+/HER2- Breast Cancer


BYLieve clinical trial data indicate long-term and very-long-term data disease control was observed in 25.6% and 16.5% of patients, respectively, with PFS at 24.8 and 29.4 months in patients with HR-positive, HER2-negative advanced breast cancer.

Patients with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) treated with alpelisib [(ALP) Piqray; Novartis] plus fulvestrant (Faslodex; AstraZeneca) post-treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) have the potential to achieve more than 2 years disease control duration, according to a poster presentation at the San Antonio Breast Conference in Texas on December 8, 2022.

Results from the BYLieve (NCT03056755) clinical trial cohort A show that in these patients, long-term (LT) and very-long-term (VLT) disease control was observed in 25.6% and 16.5%, respectively, with median progression-free survival at 24.8 months and 29.4 months, respectively.

BYLieve was a noncomparative, open-label, phase 2, 3-cohort study of alpelisib plus endocrine therapy (ET) in patients with PIK3CA-mutated, HR-positive, HER2-negative ABC whose disease progressed on/after prior treatments, including regimens with a CDK4/6i.

Development of adverse effects (AEs), ESR1 mutations, and visceral disease did not prevent LT/VLT disease control. These data confirm that targeting the PIK3CA driver mutation with ALP plus fulvestrant post-treatment with a CDK4/6i may lead to LT disease control, according to the presentation.

Compared with non-LT patients, those with LT or VLT disease control were observed to have fewer liver metastases, a longer time from initial diagnosis to first recurrence or relapse, lower body mass indexes and ECOG scores, and more frequent bone-only lesions.

In addition, prognostic factors associated with LT disease control in patients treated with ALP plus fulvestrant after treatment with a CDK4/6i were identified using multivariate modeling and included prognostic factors, such as bone-only status, longer duration of last ET in the adjuvant setting, and no detectable PIK3CA mutation in baseline circulating tumor DNA (ctDNA); patients with negative prognostic factors were able to achieve LT disease control.

Patients who experienced LT or VLT disease control had lower tumor complexity, as well as a higher rate of low ctDNA fraction (<10%) and a lower rate of chromosome 8/11 amplification at baseline than patients who experienced non-LT disease control.

The most common AEs included diarrhea, hyperglycemia, nausea, rashes, fatigue, stomatitis, vomiting, and decreased appetite.

These data help characterize patients who achieved LT disease control based on their clinical and genetic profile and confirm that targeting the PIK3CA driver mutation with ALP plus fulvestrant immediately after treatment with a CDK4/6i may lead to LT, and even VLT, disease control in patients with HR-positive, HER2-negative ABC.

PIK3CA oncogene mutations, seen in ~40% of patients with HR-positive, HER2-negative ABC, are associated with ET resistance and shorter survival, according to the presentation.


Rugo H, Chia SK, Cortes J, et al. Long-term and very-long-term disease control in patients from BYLieve study cohort A with PIK3CA-mutant, hormone-receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer. Poster presentation. San Antonio Breast Cancer Conference in Texas. December 8, 2022.

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