Browsing by Author "Howell, SJ"

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A plain language summary of the CAPItello-291 study: Capivasertib in hormone receptor-positive advanced breast cancer
(Taylor and Francis Ltd., 2024) Turner, NC; Oliveira, M; Howell, SJ; Dalenc, F; Cortés, J; Gomez, HL; Hu, X; Jhaveri, K; Krivorotko, P; Loibl, S; Murillo, SM; Park, YH; Sohn, J-H; Toi, M; Tokunaga, E; Yousef, S; Zhukova, L; de, Bruin, E; Grinsted, L; Schiavon, G; Foxley, A; Rugo, HS
What is this summary about?: This is a summary of the article discussing the results of the CAPItello-291 study. In the study, participants had advanced breast cancer that could not be completely removed with surgery, and that was diagnosed as a type of breast cancer where tumor cells had hormone receptors (HR-positive) but did not have HER2 receptors (HER2-negative). All participants were also required to have previously received treatment with a type of therapy called an aromatase inhibitor (with or without a CDK4/6 inhibitor), but over time their cancer cells had still grown or spread. The CAPItello-291 study researchers wanted to find out if a treatment combination of the medications capivasertib plus fulvestrant worked better than placebo plus fulvestrant. Capivasertib is a drug that blocks the activity of a protein called AKT, which is found inside breast cancer cells. What are the key takeaways?: The main finding was that participants who took capivasertib plus fulvestrant lived longer without their disease getting worse (progressing) compared with those treated with placebo plus fulvestrant. This is called progression-free survival. This result was seen across all participants (median progression-free survival of 7.2 months with capivasertib plus fulvestrant vs 3.6 months with placebo plus fulvestrant). It was also seen in participants whose tumors had detectable genetic alterations in genes called PIK3CA, AKT1, and/ or PTEN (median progression-free survival of 7.3 months with capivasertib plus fulvestrant vs 3.1 months with placebo plus fulvestrant). The most common side effects experienced by participants included diarrhea and different types of rash. These were as expected (given how capivasertib works). The CAPItello-291 study is still ongoing, and more results are expected to be released in the future. What were the main conclusions reported by the researchers?: Results from the CAPItello-291 study showed that capivasertib plus fulvestrant compared with placebo plus fulvestrant improved progression-free survival in participants with HR-positive/ HER2-negative advanced breast cancer whose cancer had grown or spread despite hormone therapy (with/without a CDK4/6 inhibitor). Clinical Trial Registration:NCT04305496 (CAPItello-291) (ClinicalTrials.gov).
Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer
(Massachussetts Medical Society, 2023) Turner, NC; Oliveira, M; Howell, SJ; Dalenc, F; Cortes, J; Gomez-Moreno, HL; Hu, X; Jhaveri, K; Krivorotko, P; Loibl, S; Morales-Murillo, S; Okera, M; Park, YH; Sohn, J; Toi, M; Tokunaga, E; Yousef, S; Zhukova, L; De-Bruin, EC; Grinsted, L; Schiavon, G; Foxley, A; Rugo, HS
Background AKT pathway activation is implicated in endocrine-therapy resistance. Data on the efficacy and safety of the AKT inhibitor capivasertib, as an addition to fulvestrant therapy, in patients with hormone receptor-positive advanced breast cancer are limited. Methods In a phase 3, randomized, double-blind trial, we enrolled eligible pre-, peri-, and postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer who had had a relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. Patients were randomly assigned in a 1:1 ratio to receive capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed progression-free survival assessed both in the overall population and among patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors. Safety was assessed. Results Overall, 708 patients underwent randomization; 289 patients (40.8%) had AKT pathway alterations, and 489 (69.1%) had received a CDK4/6 inhibitor previously for advanced breast cancer. In the overall population, the median progression-free survival was 7.2 months in the capivasertib-fulvestrant group, as compared with 3.6 months in the placebo-fulvestrant group (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P<0.001). In the AKT pathway-altered population, the median progression-free survival was 7.3 months in the capivasertib-fulvestrant group, as compared with 3.1 months in the placebo-fulvestrant group (hazard ratio, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The most frequent adverse events of grade 3 or higher in patients receiving capivasertib-fulvestrant were rash (in 12.1% of patients, vs. in 0.3% of those receiving placebo-fulvestrant) and diarrhea (in 9.3% vs. 0.3%). Adverse events leading to discontinuation were reported in 13.0% of the patients receiving capivasertib and in 2.3% of those receiving placebo. Conclusions Capivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients with hormone receptor-positive advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor. © 2023 Massachusetts Medical Society.