Capivasertib-fulvestrant combo helps improve life quality in advanced breast cancer

The addition of capivasertib (C) to fulvestrant (F) results in better health-related quality of life (HRQoL), except for diarrhoea, in patients with aromatase inhibitor-resistant HR-positive/HER2-negative advanced breast cancer when compared to placebo plus F, according to the phase III CAPItello-291 study presented at SABCS 2023.

“Worsening of diarrhoea was observed with C plus F, consistent with the safety profile of C, but events appeared tolerable and did not negatively impact global health status (GHS)/HRQoL,” said the researchers, led by Maflada Oliveira from the Breast Cancer Group, Vall d'Hebron Institute of Oncology, Barcelona, Catalonia, Spain.

“Together with the clinical efficacy and manageable safety profile of C plus F, the patient-reported outcome (PRO) results from the CAPItello-291 trial further support a positive benefit–risk profile of the combination in this population,” they noted.

Oliveira and colleagues randomly assigned 708 patients to receive F (500 mg IM on days 1 and 15 of cycle 1 and day 1 of each subsequent 28-day cycle) with either placebo or C (400 mg BID; 4 days on, 3 days off). Of these, 355 received C plus F and 353 placebo.

The research team assessed PRO measures, including HRQoL, disease-related symptoms, functioning, and patient-reported treatment tolerability, using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), EORTC QLQ Breast Cancer 23 items (EORTC QLQ-BR23), PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and Patient Global Impression of Treatment Tolerability (PGI-TT).

PROs were also analysed at prespecified timepoints. Change from baseline was evaluated using the Mixed Model Repeat Measures (on-treatment scores) for EORTC QLQ-C30 and summarized for EORTC QLQ-BR23. Finally, the researchers assessed time to deterioration (TTD) using the stratified log-rank test for both.

Overall compliance rates with EORTC QLQ-C30 and PGI-TT were 84.5 percent and 80.6 percent in the C plus F arm and 81.8 percent and 81.7 percent in the placebo arm, respectively. At baseline, the corresponding compliance rates were 88.2 percent and 82.8 percent in the C plus F arm, and 87.3 percent and 83.1 percent in the placebo arm, respectively. [SABCS 2023, abstract PS02-02]

Side effects

In the EORTC QLQ-C30 functional and symptom domain scores, mean changes from baseline were sustained with both treatment regimens, apart from diarrhoea in the C plus F group, wherein scores went downhill by >10 points.

In TTD analysis, C plus F trumped placebo in all functional and symptom domain scores, except again for diarrhoea (hazard ratio, 2.75, 95 percent confidence interval [CI], 2.01‒3.81), which favoured the latter. Median diarrhoea TTD was shorter with C plus F compared with placebo plus F, which was consistent with the safety profile of C.

“Diarrhoea with C plus F was generally manageable, and discontinuations due to diarrhoea were low (2.0 percent; n=7/355),” the researchers said.

Additionally, most patients found the treatment tolerable, saying that they were “not at all” or “a little bit” bothered by the side effects of cancer therapy.

“Over the first 6 months, the proportion of patients reporting to be ‘somewhat’, ‘quite a bit’, or ‘very much’ bothered by side effects was higher for C plus F vs placebo plus F, with between-arm differences being highest in the first two cycles,” the researchers said.