The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

The combination of alpelisib, a PI3Kα inhibitor, and fulvestrant demonstrated efficacy and manageable toxicity among patients with PI3KCA-mutated, hormone receptor (HR)–positive, HER2-negative, advanced breast cancer after progression with a prior regimen, including a CDK4/6 inhibitor, according to results from the phase 2 BYLieve trial presented during the ASCO20 Virtual Scientific Program.1

PI3KCA is mutated in approximately 40% of patients with HR-positive, HER2-negative advanced breast cancer, and is associated with treatment resistance and poor outcomes.

“Alpelisib and fulvestrant demonstrated efficacy in the phase 3 SOLAR-1 trial2 in patients with hormone receptor positive, PIK3CA-mutant advanced breast cancer, progressing on an aromatase inhibitor,” explained Hope S. Rugo, MD, of the University of California San Francisco Comprehensive Cancer Center, and lead author and presenter of the study. Due to the timing of SOLAR-1, only 20 patients had received a prior CDK4/6 inhibitor.

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For this reason, the phase 2 BYLieve trial ( Identifier: NCT03056755) was designed to evaluate alpelisib in women with PIK3CA-mutated advanced breast cancer who had relapsed after prior therapy, including a CDK4/6 inhibitor.

The ongoing, open-label, phase 2 trial plans to enroll 112 patients to each of 3 cohorts: patients who received an immediate prior CDK4/6 inhibitor plus an aromatase inhibitor; patients who received an immediate prior CDK4/6 inhibitor and fulvestrant; and patients who received prior systemic chemotherapy or patients who received prior endocrine therapy only. Enrollment for the first 2 cohorts is completed; this analysis is of the first cohort.

In this analysis, 121 patients with PI3KCA-mutated, HR-positive, HER2-negative advanced breast cancer who had previously received a CDK4/6 inhibitor and an aromatase inhibitor were treated with alpelisib plus fulvestrant. The primary endpoint was 6-month progression-free survival (PFS) by local assessment.

Among patients in the first cohort at baseline, the median age was 58 and most patients had an Eastern Cooperative Oncology Group performance status of 0 (62.2%) or 1 (23.3%). Nearly all patients had primary or secondary resistance to endocrine therapy.

The cohort met the primary endpoint, with a 6-month PFS of 50.4% (95% CI, 41.2%-59.6%). The median PFS was 7.3 months (95% CI, 5.6-8.3 months).

Compared with a real-world cohort of patients from the US Flatiron Health Foundation Medicine clinicogenomics database, the median PFS was 3.6 months with standard treatment compared with 7.3 months with alpelisib/fulvestrant.

The overall response rate was 17.4%, which were all partial responses. The proportion of patients with stable disease was 45.5% and progressive disease was 11.6%.

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The most common grade 3 or higher adverse events (AEs) were hyperglycemia (28%), rash (9%), and diarrhea (5.5%). Treatment discontinuation due to AEs occurred in 20.5% of cases and 64.6% of patients required dose interruption or adjustment.

Any grade rash occurred in 28% of patients, but Dr Rugo noted that “prophylactic antihistamines may decrease the occurrence and severity of rash that can occur on alpelisib.”

“Considering SOLAR-1 and a real-world evidence analysis, BYLieve supports the use of alpelisib and fulvestrant for [HR-positive] advanced breast cancer in the post-CDK4/6 inhibitor setting and confirms findings that were observed in SOLAR-1,” Dr Rugo concluded.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.


  1. Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib (ALP) + fulvestrant (FUL) in patients (pts) with PIK3CA-mutated (mut) hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) previously treated with cyclin-dependent kinase 4/6 inhibitor (CDKi) + aromatase inhibitor (AI): BYLieve study results. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 1006.  
  2. André F, Ciruelos E, Rubovsky G, et al. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med. 2019;380:1929-1940.