Capivasertib Plus Palbociclib and Fulvestrant Demonstrated Safety, Tolerability Among Patients With HR-Positive, HER2-Negative Advanced Breast Cancer

Updated Phase 1b Results From the CAPItello-292 Trial

According to updated phase 1b results from the CAPItello-292 study, capivasertib plus palbociclib and fulvestrant was safe and tolerable among heavily pre-treated patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. 

As previously reported “in CAPItello-291, capivasertib (a potent inhibitor of all 3 AKT isoforms) + fulvestrant significantly improved [progression-free survival] PFS versus placebo + [fulvestrant],” stated Erika Hamilton, MD, Sarah Cannon Research Institute, Nashville, Tennessee, and coauthors. “The recommended phase 3 dose of [capivasertib plus palbociclib and fulvestrant] has been determined (400 mg [twice daily capivasertib], 4 days on/3 days off, 125 mg [palbociclib], 500 mg [fulvestrant]).”

In this keyboard design analysis, 40 patients who received ≥1 prior line of endocrine therapy or experienced disease recurrence within 12 months of completing neo/adjuvant endocrine therapy were enrolled to receive planned doses of capivasertib (200 mg, 320 mg, and 400 mg) and palbociclib (75 mg, 100 mg, and 125 mg) plus 500 mg of fixed fulvestrant every 28 days. The starting dose was 320 mg of twice-daily capivasertib for 4 days on and 3 days off, plus 125 mg of palbociclib 4 times daily for 21 days, and fixed fulvestrant plus an additional loading dose administered on cycle 1 day 15. Primary end points included safety, tolerability, and confirmation of the recommended phase 3 dosage. Secondary end points included objective response rate (ORR) and 24-week clinical benefit rate. 

At the data cut-off point, no new dose-limiting toxicities were reported and the most frequent adverse events occurring in >40% of patients included diarrhea, neutropenia, fatigue, and nausea. Hyperglycemia occurred in 17.5% of patients and no new treatment-related deaths or safety risks were identified. At the recommended phase 3 dose, the median duration of capivasertib exposure was 8.6 months and the ORR was 62.5%. At 24-weeks, the clinical benefit rate was 53.8%. 

Dr Hamilton and coauthors concluded, capivasertib plus palbociclib and fulvestrant was “tolerable in heavily pre-treated [patients] with HR+/HER2– [advanced breast cancer] at all dose levels. Data collection is ongoing; more [patients] and longer follow-up is required to characterize the safety of the combination."

Source: 

Hamilton E, Neven P, Pistilli B, et al. Capivasertib plus cyclin-dependent kinase 4/6 inhibitor and fulvestrant in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Updated Phase 1b analysis from CAPItello-292. Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023. San Antonio, Texas. Abstract PS12-09