Alpelisib Plus Fulvestrant Continues to Show Improved PFS in PIK3CA-Mutant, HR+, HER2- Advanced Breast Cancer
Alpelisib plus fulvestrant consistently resulted in prolonged PFS among patients with HR+, HER2– advanced breast cancer who also had PIK3CA mutations.
|The following article features coverage from the San Antonio Breast Cancer Symposium (SABCS) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.|
Alpelisib (ALP) plus fulvestrant (FUL) consistently prolonged progression-free survival (PFS) compared with placebo plus FUL across subgroups among patients with advanced hormone receptor (HR)-positive, HER2-negative breast cancer who had PIK3CAmutations, according to data from the SOLAR-1 trial presented at the 2018 San Antonio Breast Cancer Symposium in San Antonio, Texas.1
The double-blind, phase 3 SOLAR-1 trial met its primary end point of improved PFS with ALP plus FUL treatment compared with placebo among patients with PIK3CA mutations (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.50-0.85; P = .0007). This analysis provides the overall survival (OS), subgroup data, and safety information across the PIK3CA-mutant cohort.
The SOLAR-1 trial included 341 patients with HR-positive, HER2-negative advanced breast cancer with a PIK3CAmutation who had received 1 prior line of endocrine therapy. Patients were randomly assigned to receive ALP plus FUL or placebo plus FUL with a median follow-up of 20.0 months at data cutoff. The primary end point was PFS in this cohort, and a key secondary end point was OS.
At data cutoff, the OS data were immature, but trended toward improvement with the addition of ALP, with a median OS deemed not estimable, compared with 26.9 months with placebo (HR, 0.73; 95% CI, 0.48-1.10; P = .06).
In the subgroup analyses, there was a 45% decrease in risk of PFS among patients who harbored aPIK3CAmutation in their circulating tumor DNA (ctDNA) (HR, 0.55; 95% CI, 0.39-0.79), which was consistent with the primary endpoint. There was no significant difference between arms for patients without a PIK3CAmutation in ctDNA (HR, 0.80; 95% CI, 0.60-1.06).
ALP plus FUL treatment consistently prolonged PFS across most subgroups compared with placebo, including patients who had received 1 or 2 prior lines of therapy, and patients who previously received a CDK4/6 inhibitor.
ALP plus FUL was associated with greater rates of some all-grade adverse events (AEs) than placebo, with the most common including hyperglycemia (55% vs 9%), diarrhea (54% vs 11%), nausea (46% vs 20%), and rash (40% vs 6%). The most common grade 3/4 AEs in the ALP plus FUL arm compared with placebo were hyperglycemia (37% v < 1%) and rash (13% vs < 1%). AEs leading to discontinuation of therapy was similar between arms, with 3% in the ALP plus FUL group and 2% in the placebo group.
The authors concluded that these data suggest that ALP plus FUL “showed consistent clinically meaningful treatment benefit for patients with ctDNA PIK3CA-mutant status, and across subgroups.”
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Juric D, Ciruelos E, Rubovszky G, et al. Alpelisib + fulvestrant for advanced breast cancer: Subgroup analyses from the phase III SOLAR-1 trial. Presented at: 2018 San Antonio Breast Cancer Symposium; San Antonio, TX; December 4-8, 2018. Abstract GS3-07.