In patients with HR+/HER2[ES1] - advanced breast cancer, the unique mutation profile of PIK3CA-altered tumors did not affect aplelisib and fulvestrant benefit, according to findings presented at the 2022 ASCO Annual meeting.

This phase 3, randomized, double-blind SOLAR-1 study focused on alpelisib or placebo + fulvestrant in patients with HR+, HER2- advanced breast cancer processing on/after an aromatase inhibitor.

Authors of the study retrospectively tested 398 baseline tissue samples with enough quantity/quality and included patients were grouped by PIK3CA-alteration status. Progression-free survival and hazard ratio based on tumor mutational burden and gene alteration status in the PIK3CA-altered cohort were utilized to assess clinical benefit.

Differential gene alteration landscapes were observed in PIK3CA-altered (ALP, n=120; PBO, n=117) and PI3KCA-non-altered (ALP, n=81; PBO, n=80) cohorts.

Alpelisib and fulvestrant showed greater benefit among patients with altered vs non-altered FGFR1/2 and clinical benefit in the PIK3CA-altered cohort was observed across TMB quartiles TMB quartiles (Q1: 0 -<2.52, Q2: 2.52 -<3.78, Q3: 3.78 -<5.04, Q4: ≥ 5.04 mut/megabase). 

In TP53, ESR1, CCND1, MAP3K1, and ARID1A and limited in MYC- and RAD21-alt cohorts alpelisib and fulvestrant benefit was independent of alterations. Patients with alt genes in MAPK (HR [95% CI] vs PBO: altered 0.43 [0.23-0.80]; non-altered 0.56 [0.40-0.79]) and PI3K (in addition to PIK3CA; altered 0.68 [0.38-1.23]; non-altered 0.48 [0.34-0.68]) pathways, and implicated in CDK4/6i resistance (altered 0.52 [0.30-0.89]; non-altered 0.53 [0.37-0.76] saw full benefit from alpelisib and fulvestrant treatment.

“Clinical benefit was maintained regardless of alterations in most biomarkers, including ESR1 and genes implicated in CDK4/6i resistance, consistent with alpelisib targeting the PIK3CA driver oncogene,” concluded researchers.

Reference:
Juric D, Rugo HS, Reising A, et al. Alpelisib (ALP) + fulvestrant (FUL) in patients (pts) with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC): Biomarker (BM) analyses by next-generation sequencing (NGS) from the SOLAR-1 study. J Clin Oncol. 2022;40(suppl 16): abstract 1006. doi:10.1200/JCO.2022.40.16_suppl.1006