What question did this study set out to answer?

This research aims to evaluate the long-term benefits of geda combination therapy in advanced breast cancer previously treated with CDK4/6 inhibitors.

May 24, 2026Open Access

507P Determinants of long-term chemo-immunotherapy benefit in advanced triple-negative breast cancer

Key Points

This research aims to evaluate the long-term benefits of geda combination therapy in advanced breast cancer previously treated with CDK4/6 inhibitors.
Phase 3 VIKTORIA-1 trial; randomized controlled trial design
Eligible patients had hormone receptor-positive, HER2-negative breast cancer and showed radiological disease progression after prior treatments
Participants were assigned to receive either geda with palbociclib and fulvestrant, geda with fulvestrant, or fulvestrant alone.
Study 1 met co-primary endpoints, showing significant progression-free survival (mPFS: 9.3 months for triplet vs 2.0 months for fulv, HR 0.24, 95% CI 0.17-0.35, P<0.0001)
Quality of life assessments indicated geda improved median time to deterioration compared to fulvestrant
Geda did not cause significant hyperglycemia and led to timely management of treatment-related stomatitis.

Abstract

Background:The PAM pathway drives breast cancer growth and resistance to endocrine therapy (ET) and CDK4/6i.Combining PAM inhibition with ET + CDK4/6i after progression may restore sensitivity and provide benefit independent of PI3Kpathway alterations.Geda, a potent pan-Class I PI3K and mTORC1/2 inhibitor, blocks PAM regardless of PIK3CA status.The phase 3 VIKTORIA-1 trial evaluates geda-based therapy in pts with HR+/HER2-ABC that progressed on or after standard therapy.Pts are enrolled to Study 1 or Study 2 based on PIK3CA status (WT vs mutated).Here, we encore updated subgroup, safety, and QOL data from Study 1.Methods: Eligible pts had HR+/HER2-ABC that progressed on/after CDK4/6i + nonsteroidal AI and radiologically evaluable disease (per RECIST v1.1) with no prior chemo for ABC, nor prior PAMi.Study 1 pts were randomized to geda + palbo + fulv (triplet), geda + fulv (doublet), or fulv alone, stratified by visceral mets, time to radiological disease progression (TTP) on immediate prior therapy, and geographic region.Results: As previously reported, Study 1 met its co-primary endpoints, demonstrating statistically and clinically meaningful PFS with geda (mPFS, 9.3 vs 2.0 months for triplet vs fulv [HR, 0.24; 95% CI, 0.17-0.35;P6, >12, >18, and >24 months) and in bone-only disease.Median time to onset of treatment-related stomatitis was generally within the first treatment week.Median time to improvement from worst grade was within 2 weeks.Geda did not produce clinically relevant hyperglycemia.QOL perEQ-5D-5L showed improvements in median time to deterioration for the geda arms vs fulv.EQ-5D-5L scores remained stable with geda from cycles 1 to 8. With fulv, declines began at cycle 6 and remained below baseline at cycle 8.Conclusions: These data support geda combo therapy as a potential new standard of care for the 2L treatment of pts with HR+/HER2-/PIK3CA WT ABC.

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