ASCO 2026: Sima Ehsani Chimeh, MD, on the VIKTORIA-1 Trial in HR+/HER2-Negative Advanced Breast Cancer

At a Glance

• VIKTORIA-1 is a phase 3 trial evaluating gedatolisib, a pan-PI3K/mTORC1/2 inhibitor, in combination with fulvestrant with or without palbociclib in HR+/HER2-negative advanced breast cancer following progression on a CDK4/6 inhibitor and aromatase inhibitor
• Gedatolisib-based therapy roughly doubled PFS compared with alpelisib plus fulvestrant in the PIK3CA-mutant cohort
• Gedatolisib showed lower rates of hyperglycemia than alpelisib, addressing a key tolerability concern with current PI3K-targeted therapy
• Mature overall survival data are pending; VIKTORIA-2 will evaluate gedatolisib in first-line settings

Best of Breast at ASCO

At the 2026 ASCO Annual Meeting, the VIKTORIA-1 trial emerged as a significant update in the management of HR-positive, HER2-negative advanced breast cancer, presenting data for gedatolisib (a pan-PI3K and mTORC1/2 inhibitor) in patients with PIK3CA-mutant, endocrine-resistant disease. Sima Ehsani Chimeh, MD, offered her perspective on the trial’s findings and what they mean for clinical practice.

VIKTORIA-1: Promising Direction for Endocrine-Resistant Disease

“VIKTORIA-1 is a phase III study evaluating gedatolisib, a potent pan-PI3K and mTORC1/2 inhibitor, in combination with fulvestrant with or without palbociclib in patients with HR-positive, HER2-negative advanced breast cancer following progression on a CDK4/6 inhibitor and aromatase inhibitor,” Ehsani explained. “The PIK3CA-mutant cohort presented at ASCO 2026 demonstrated improved progression-free survival with gedatolisib-based therapy compared with alpelisib plus fulvestrant.”

In other words, the study “introduces a potentially effective new therapeutic option for patients with endocrine-resistant disease while addressing some of the limitations of current PI3K-targeted therapies, including lower rates of hyperglycemia compared with alpelisib.”

Results and Implications

“The pan-PI3K/mTOR inhibitor gedatolisib, in combination with palbociclib/fulvestrant or fulvestrant alone, roughly doubled progression-free survival (PFS) compared to alpelisib/fulvestrant in patients with HR+/HER2-advanced breast cancer,” Ehsani said. “This data could potentially change current practice as the new treatment improved PFS, while addressing some of the limitations of current PI3K targeted therapies such as lower rates of hyperglycemia compared with alpelisib.”

Going Forward

The data are promising, but concrete conclusions must precede at-scale clinical impact. “Important questions remain regarding the optimal use of doublet versus triplet therapy and the practical implications of intravenous administration of gedatolisib,” Ehsani said. “We still need the mature, overall survival data from this study. VIKTORIA-2 trial is going to evaluate gedatolisib in first-line settings. Additional efforts focus on developing a subcutaneous formulation to replace intravenous infusions.”