Capivasertib Shows Superior PROs Vs Placebo in HR+, HER2- Breast Cancer


Patient-reported outcomes of the CAPItello-291 study of capivasertib plus fulvestrant showed a positive benefit-risk profile for the combination in patients with HR-positive, HER2-negative advanced breast cancer.

Breast Cancer: © SciePro -

Breast Cancer: © SciePro -

The combination of capivasertib (Truqap) plus fulvestrant (Faslodex) in patients with hormone receptor (HR)­–positive, HER2-negative breast cancer demonstrated that health-related quality of life (HRQOL) was maintained longer compared with placebo plus fulvestrant, according to the patient-reported outcome (PRO) results of the CAPItello-291 trial (NCT04305496).1

At the 2023 San Antonio Breast Cancer Symposium, Mafalda Oliveira, MD, PhD, discussed the PROs from the phase 3 CAPItello-291 study using data from 3 PRO questionnaires. These included the EORTC QLQ-C30, EORTC QLQ-BR23, and the Patient Global Impression of Treatment Tolerability.

In previously reported data, patients with aromatase inhibitor (AI)-resistant advanced breast cancer showed significant improvement with capivasertib vs placebo in terms of progression-free survival (PFS) in the overall population and in patients with PIK3CA/AKT1/PTEN-altered disease.2

“As new targeted drugs are approved for the treatment of breast cancer, assessment of HRQOL and patient experience is of growing importance and can actually supplement evaluation of the risk-benefit profile of treatment,” Oliveira, a medical oncologist in the Department of Medical Oncology at Vall d'Hebron University Hospital in Spain, said in her presentation.1

The EORTC QLQ-C30 and EORTC QLQ-BR23 functional and symptom domains, except for diarrhea, were maintained in patients receiving with the capivasertib combination longer than for those receiving placebo. There was more than a 10-point change in diarrhea symptom scores in the QLQ-C30 for capivasertib, which was consistent with its known safety profile.

In CAPItello-291, 708 patients were randomly assigned to the capivasertib/fulvestrant arm (n = 355) or the placebo/fulvestrant arm (n = 353). For all 3 PRO assessments, the baseline and overall compliance rates were similarly high between treatment arms, above 80% for each, and though compliance was lower up to cycle 6, it was similar between arms.

The mean baseline scores for EORTC QLQ-C30 were similar between the 2 arms across subscales, and both arms had consistent global health status (GHS)/QOL scores maintained from baseline. There was a least squares mean change from baseline with capivasertib of -1.0 to -5.3 and -1.8 to -9.6 with placebo. Capivasertib was not associated with clinically meaningful changes in the functional and symptom domain scores for EORTC QLQ-C30, except for a worse score for diarrhea.

In the EORTC QLQ-C30 and QLQ-BR23, time to deterioration (TTD) for GHS/QOL was longer for patients in the capivasertib/fulvestrant arm. Except for diarrhea, the EORTC QLQ-C30 TTD for functional domains and symptom scales favored capivasertib numerically, including in pain and fatigue. Diarrhea with capivasertib/fulvestrant was grade 1/2 in 63.1% of patients, and the combination led to low rates of dose reductions, interruptions, and discontinuations in 7.9%, 9.9%, and 2.0% of patients, respectively. The TTD also numerically favored capivasertib in the EORTC QLQ-BR23.

Both treatment arms reported that most patients were either “not at all” or “a little bit bothered by adverse events (AEs) from therapy in the Patient Global Impression of Treatment Tolerability assessment. In the first 2 cycles, the treatment differences were the highest, with more patients receiving capivasertib reporting they were “somewhat,” “quite a bit,” or very much” bothered by AEs. However, these differences subsided after cycle 2.

The methods used for assessment of PROs using EORTC QLQ-C30 and EORTC QLQ-BR23 required patients to complete these questionnaires on day 1 of cycle 1 and every 4 weeks until second progression and at the progression or discontinuation visit. For the Patient Global Impression of Treatment Tolerability questionnaire, patients were to complete it on day 1 of cycle 1 and every 2 weeks after, then every 4 weeks after week 12 until discontinuation, and 4 weeks after discontinuation.

In the phase 3, double-blind, randomized CAPItello-291 trial, the overall population of patients with HR-positive, HER2-negative, AI-resistant advanced breast cancer given capivasertib/fulvestrant had a median PFS of 7.2 months vs 3.6 with placebo/fulvestrant (HR, 0.60; 95% CI, 0.51-0.71; P < .001).2 Patients with AKT pathway alterations (69.1%) had a median PFS of 7.3 months vs 3.1 months for capivasertib vs placebo, respectively (HR, 0.50; 95% CI, 0.38-0.65; P < .001).

“In conclusion, together with the clinical efficacy and manageable safety profile of capivasertib plus fulvestrant, the results of this PRO analysis further support positive benefit-risk profile for the combination of capivasertib and fulvestrant in AI-resistant, HR-positive, HER2-negative advanced breast cancer,” Oliveira said.

1. Rugo H, Oliveira M, Howell S, et al. Patient-reported outcomes from the Phase 3 CAPItello-291 trial investigating capivasertib and fulvestrant for patients with aromatase inhibitor-resistant HR-positive/HER2-negative advanced breast cancer. Presented at: San Antonio Breast Cancer Conference; December 5-9, 2023; San Antonio, TX. Abstract PS02-02.
2. Turner NC, Oliveira M, Howell SJ, et al; CAPItello-291 Study Group. Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med. 2023;388(22):2058-2070. doi:10.1056/NEJMoa2214131
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