KEY TAKEAWAYS
- The phase Ib/III study assessed the safety and effectiveness of C+P+F versus a placebo+P+F in HR+/HER2− ABC patients.
- Phase Ib’s primary endpoints were safety/tolerability and RP3D confirmation.
- The study suggested that C+P+F was well-tolerated in extensively pre-treated HR+/HER2− ABC patients.
Activation of the AKT pathway is linked to reduced responsiveness to both endocrine therapy (ET) and cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in patients (pts) with hormone receptor-positive, HER2-negative advanced breast cancer (HR+/HER2− ABC).
The CAPItello-291 study showed that combining C+F notably prolonged progression-free survival compared to F alone in pts with aromatase inhibitor-resistant HR+/HER2− ABC. This was also true for pts whose tumors had altered AKT pathways. Inhibiting AKT and CDK4/6 pathways simultaneously could enhance clinical results by making tumors more responsive to ET and CDK4/6i.
The phase Ib/III study examined the safety and effectiveness of the C+P+F combination versus a placebo+P+F in HR+/HER2− ABC. The phase Ib part employed a Keyboard design (mTPI-2) and allowed prior CDK4/6i treatments. It mainly focused on safety, tolerability, and establishing the recommended dose for phase III (RP3D). Ongoing liquid biopsy (ctDNA) monitoring and drug pharmacokinetics were also conducted. Data was reviewed as of October 31, 2022.
The study included 39 pts who had undergone extensive prior treatments, with a median age of 59 years. Seven dose-limiting toxicities (DLTs), mostly related to neutropenia, were observed in 6 pts but did not hinder dose escalation or expansion. The combination C400+P125+F500 was finalized as the RP3D. The most frequent side effects included diarrhea, neutropenia, fatigue, and nausea. No new safety issues or treatment-related deaths were reported. Preliminary data on efficacy and ctDNA for pts treated at the RP3D will be shared.
The combination of C+P+F was generally well-tolerated in this patient group and aligned with anticipated safety outcomes. There were no significant safety disparities among different dosage levels. DLTs were in line with what was expected.
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04862663
Neven, P., Hamilton, E., Pistilli, B., Borges, V., Campone, M., Foukakis, T., Kodahl, A.R., Lau, P.K.H., Lim, E., Lugowska, I., Collins, J., Gresty, C., Miller, C., Sommavilla, R., Sudhan, D., Rugo, H.S. 206P – Capivasertib (C) + palbociclib (P) and fulvestrant (F) in patients (pts) with HR+/HER2_ advanced breast cancer (ABC): Phase 1b data from CAPItello-292. Annals of Oncology (2023) 8 (1suppl_4): 101223-101223. 10.1016/esmoop/esmoop101223
