Capivasertib-Fulvestrant Maintains Quality of Life While Improving PFS in HR-Positive Breast Cancer

Original abstract

BACKGROUND: CAPItello-291 is an ongoing phase 3 trial in which capivasertib-fulvestrant significantly improved progression-free survival versus placebo-fulvestrant in patients with hormone receptor-positive, HER2-negative advanced breast cancer who had relapse or disease progression during or after aromatase inhibitor treatment, in both the overall population and in patients with PIK3CA, AKT1, or PTEN-altered tumours. This study further explored patient-reported health-related quality of life (HRQOL), functioning, symptoms, and symptom tolerability in CAPItello-291. METHODS: This phase 3, randomised, double-blind, placebo-controlled trial, which was conducted across 193 hospitals and cancer centres in 19 countries, enrolled women with any menopausal status or men, aged ≥18 years (≥20 years in Japan), with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer who had relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase (CDK) 4 or 6 inhibitor therapy. Patients had an Eastern Cooperative Oncology Group/WHO performance score of 0 or 1 and could have received up to two previous lines of endocrine therapy and up to one previous line of chemotherapy for advanced disease. Patients were randomly assigned (1:1) using block randomisation (stratified according to the presence or absence of liver metastases, previous use of a CDK4/6 inhibitor [yes vs no], and geographical region) to receive oral capivasertib 400 mg (twice daily for 4 days, followed by 3 days off) plus intramuscular fulvestrant 500 mg (every 14 days for the first three injections, then every 28 days) or placebo with matching fulvestrant dosing. The dual primary endpoint of the trial was investigator-assessed progression-free survival assessed both in the overall population and among patients with PIK3CA, AKT1, or PTEN-altered tumours. The EORTC Quality of Life Questionnaire 30-item core module (QLQ-C30) and breast module (QLQ-BR23), Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and Patient Global Impression of Treatment Tolerability (PGI-TT) questionnaires were used to assess patient-reported outcomes. Evaluation of EORTC QLQ-C30 and EORTC QLQ-BR23 were secondary endpoints and evaluation of PRO-CTCAE and PGI-TT were pre-defined exploratory endpoints, and these endpoints are the subject of analysis in this Article. Data were collected at baseline and prespecified timepoints. Patient-reported outcomes were analysed in all randomly assigned patients with an evaluable baseline assessment and at least one evaluable post-baseline assessment. Change from baseline was assessed using mixed model with repeated measures for EORTC QLQ-C30 and summarised for QLQ-BR23. Time to deterioration was described using the Kaplan-Meier method. PGI-TT and PRO-CTCAE responses were summarised at each treatment cycle. Patient-reported outcomes were not prospectively powered for statistical comparison. The trial is registered with ClinicalTrials.gov, NCT04305496. FINDINGS: Between June 2, 2020, and Oct 13, 2021, 901 patients were enrolled, of whom 708 patients were randomly assigned to receive capivasertib-fulvestrant (n=355) or placebo-fulvestrant (n=353). The median age of the patients was 59 years (IQR 51-67) in the capivasertib-fulvestrant group and 58 years (IQR 49-66) in the placebo-fulvestrant group. At data cutoff (Aug 15, 2022), the median duration of follow-up for progression-free survival in censored patients was 13·0 months (IQR 9·1-16·7) for capivasertib-fulvestrant and 12·7 months (IQR 2·0-16·4) for placebo-fulvestrant in the overall population. EORTC QLQ-C30 global health status/quality of life (GHS/QOL) scores were maintained from baseline and were similar between treatment groups throughout the study period (difference in mean change from baseline of -2·5 [95% CI -4·5 to -0·6] with capivasertib-fulvestrant vs -5·6 [-7·