Gedatolisib-Based Combinations Demonstrate Improved Progression-Free Survival and Durable Responses in PIK3CA-Mutated Advanced Breast Cancer
VIKTORIA-1 (NCT05501886) is a randomized, open-label Phase III study evaluating gedatolisib in combination with fulvestrant, with or without palbociclib, compared with standard-of-care treatment in patients with HR+/HER2− locally advanced or metastatic breast cancer. The presented analysis focused on Study 2, involving patients with PIK3CA-mutated advanced breast cancer who had previously received CDK4/6 inhibitor and endocrine therapy.
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Key Efficacy and Safety Highlights | ||||
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Category |
Parameter |
Gedatolisib Triplet (n=133) |
Gedatolisib Doublet (n=42*) |
Alpelisib + Fulvestrant (n=127*) |
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Efficacy |
Median PFS – No liver metastases |
21.5 months |
11.5 months |
9.1 months |
|
PFS hazard ratio – No liver metastases |
0.46 |
0.71 |
Comparator | |
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PFS statistical significance – No liver metastases |
p=0.0016 |
p=0.1627 |
- | |
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Median PFS – Liver metastases |
9.1 months |
11.1 months |
4.6 months | |
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PFS hazard ratio – Liver metastases |
0.47 |
0.38 |
Comparator | |
The study evaluated two gedatolisib-based regimens: the triplet combination of gedatolisib + fulvestrant + palbociclib and the doublet combination of gedatolisib + fulvestrant, against alpelisib + fulvestrant. The updated presentation included subgroup analyses according to the presence or absence of liver and visceral metastases, along with an assessment of ORR, duration of response, and treatment-emergent adverse events.
The results demonstrated that both gedatolisib-based combinations improved median PFS compared with alpelisib + fulvestrant across patients with liver and visceral metastases. The triplet combination showed particularly encouraging results among patients without liver metastases, achieving a median PFS of 21.5 months compared with 9.1 months in the control arm. Additionally, the gedatolisib triplet demonstrated a higher ORR and longer median duration of response, accompanied by fewer treatment discontinuations due to adverse events.
Conclusion-
The updated Phase III VIKTORIA-1 findings demonstrate the potential of gedatolisib-based combinations to improve treatment outcomes in patients with PIK3CA-mutated HR+/HER2− advanced breast cancer following CDK4/6 inhibitor and endocrine therapy. Both the gedatolisib triplet and doublet demonstrated improved PFS across important metastatic subgroups compared with alpelisib + fulvestrant, with the triplet showing particularly strong results in patients without liver metastases. The higher ORR, prolonged duration of response, and lower treatment discontinuation rates further support the clinical potential of gedatolisib-based regimens. These findings are relevant to the evolving post-CDK4/6 treatment landscape, where overcoming pathway-mediated resistance and improving response durability remain important therapeutic priorities. If supported by further clinical and regulatory assessments, gedatolisib-based combinations could offer an important treatment option for patients with PIK3CA-mutated advanced breast cancer.