VIKTORIA-1 Trial: Post-CDK4/6 Therapy for Endocrine-Resistant Breast Cancer

In an interview with Targeted Oncology, Sara Hurvitz, MD, Fred Hutch Cancer Center, discusses the VIKTORIA-1 trial presented at the 2025 ESMO Congress. The discussion focuses on treatment options and outcomes for patients with hormone receptor-positive, HER2-negative advanced breast cancer who have experienced disease progression following initial therapy with a CDK4/6 inhibitor.

Hurvitz first highlights the significant clinical challenge faced by this patient population. She notes that following progression on frontline CDK4/6 inhibitor therapy, subsequent treatment with single-agent endocrine therapy typically yields disappointing results. Specifically, most studies examining this approach have demonstrated a progression-free survival (PFS) rate of less than 6 months. This underscores the urgent need for more effective and durable treatment strategies for patients whose disease has become relatively resistant to standard endocrine-based regimens.

A key focus of her commentary was the VIKTORIA-1 study, which investigated novel treatment combinations with gedatolisib in this post-CDK4/6 setting. Hurvitz reports that the trial successfully met its primary end point, demonstrating a statistically significant improvement in PFS for 2 different experimental arms compared to the control arm of fulvestrant monotherapy.

The first arm that showed superiority was a triplet combination consisting of gedatolisibcombined with the selective estrogen receptor degrader (SERD) fulvestrant and the CDK4/6 inhibitor palbociclib (Ibrance). The second arm that was also statistically significantly better than fulvestrant alone was a doublet combination of gedatolisib and fulvestrant. Hurvitz emphasized that both the triplet and the doublet combinations provided a statistically significant clinical benefit over the single-agent endocrine therapy.

Beyond efficacy, the discussion also touches upon the practical consideration of the adverse effect profile, an "important consideration" when selecting a treatment regimen, particularly for combination therapies. This point serves as a crucial reminder that the tolerability of a regimen is as important as its efficacy when treating patients with advanced disease.

Finally, Hurvitz remarks that the efficacy data from VIKTORIA-1 were "pretty impressive," even extending to a subset of patients with particularly endocrine-resistant breast cancer. She specifically notes that the triplet combination seemed "particularly impressive" in this highly resistant group, suggesting a potential role for this intensified regimen in patients with the most challenging disease characteristics. The overall findings from VIKTORIA-1 offer new, more effective combination strategies to extend disease control for patients who have progressed after frontline CDK4/6 inhibitor therapy, moving beyond the limitation of single-agent endocrine therapy.