As reported in The Lancet Oncology by Oliveira et al, patient-reported outcomes in the phase III CAPItello-291 trial indicate a delay in deterioration of health-related quality of life (HRQOL) with capivasertib/fulvestrant vs placebo/fulvestrant in patients with previously treated hormone receptor–positive, HER2-negative advanced breast cancer. The trial showed that capivasertib/fulvestrant significantly improved progression-free survival vs placebo/fulvestrant in patients with disease progression or relapse during or after aromatase inhibitor treatment.
Study Details
In the international double-blind trial, 708 patients were randomly assigned between June 2020 and October 2021 to receive capivasertib/fulvestrant (n=355) or placebo/fulvestrant (n=353). HRQOL was assessed by the EORTC Quality of Life Questionnaire 30-item core module (QLQ-C30) and breast module (QLQ-BR23), the Patient Global Impression of Treatment Tolerability (PGI-TT) questionnaire, and the patient-reported outcome version of CTCAE (PRO-CTCAE).
Key Findings
QLQ-C30 global health status/quality of life (GHS/QOL) scores were maintained from baseline and were similar between groups during the study period. The difference in mean change from baseline was −2.5 points (95% confidence interval [CI] = −4.5 to −0.6 points) in the capivasertib/fulvestrant group vs −5.6 points (95% CI = −7.9 to −3.4 points) in the placebo/fulvestrant group, yielding a difference of 1 point (95% CI = 0.2 to 6.0 points).
Median time to deterioration in GHS/QOL was 24.9 months (95% CI = 13.8 months to not reached) in the capivasertib/fulvestrant group vs 12.0 months (95% CI = 10.2–15.7 months) in the placebo/fulvestrant group (hazard ratio [HR] = 0.70, 95% CI = 0.53–0.92). Little difference in time to deterioration for all QLQ-C30 and QLQ-BR23 subscale scores was observed between groups; the exception was diarrhea, which was worse in the capivasertib/fulvestrant group (HR = 2.75, 95% CI = 2.01–3.81).
In PRO-CTCAE assessment, the proportion of patients reporting loose and watery stools “frequently” or “almost constantly” was 29% higher at cycle 1, day 15, in the capivasertib/fulvestrant group, with the proportion decreasing over subsequent cycles. Other PRO-CTCAE symptoms were absent or mild in most patients in both groups throughout treatment. PGI-TT analysis indicated that most patients in both groups reported “not at all” or “a little bit” of bother from treatment side effects.
The investigators concluded: “Patient-reported outcomes from CAPItello-291 demonstrated that capivasertib/fulvestrant delayed time to deterioration of GHS/QOL and maintained other dimensions of HRQOL (except symptoms of [diarrhea]) similarly to fulvestrant. With the clinical efficacy and manageable safety profile, these exploratory results further support the positive benefit–risk profile of capivasertib/fulvestrant in this population.”
Mafalda Oliveira, MD, PhD, of the Breast Cancer Unit, Vall d’Hebron Institute of Oncology, Barcelona, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by AstraZeneca. For full disclosure of all study authors, visit thelancet.com.
