Efficacy and Safety of Capivasertib vs. Alpelisib in PIK3CA-aBC

For patients with HR-positive, HER2-negative, PIK3CA-altered advanced breast cancer (aBC) with disease progression following endocrine-based therapy, FDA approved treatments include alpelisib-fulvestrant (PIK3CA-altered only) and capivasertib-fulvestrant (PIK3CA/AKT1/PTEN-altered). In the SOLAR-1 (NCT02437318) and CAPItello-291 (NCT04305496) phase 3 studies, these regimens demonstrated significantly improved progression-free survival (PFS) versus placebo-fulvestrant.

As there are no head-to-head studies between regimens, de Wilt E and the team aimed to assess the relative efficacy and safety of capivasertib-fulvestrant versus alpelisib-fulvestrant for PIK3CA-altered aBC via indirect treatment comparison (ITC).

They performed an inclusive analysis using anchored Bayesian ITCs on investigator-assessed PFS, any grade adverse event (AE) leading to treatment discontinuation, any grade 3 or 4 AE, and relevant individual AEs. The efficacy ITC was conducted on a (log) hazard ratio (HR) scale using published data from PIK3CA-altered subgroups of the SOLAR-1 and CAPItello-291 studies. Safety ITCs were performed on a risk difference (RD) scale using aggregate data from the safety analysis set of each study. HR and RD estimates were calculated alongside 95% credible intervals (95% CrI).

For PFS, the HR for capivasertib-fulvestrant versus alpelisib-fulvestrant was 0.79 (95% CrI 0.52 to 1.18). The Bayesian probability of capivasertib-fulvestrant being more efficacious (HR<1) than alpelisib-fulvestrant was 87%. The safety RD (95% CrI) ITC results suggest nominally significant risk reductions (RD<0.00) for capivasertib-fulvestrant in any AE leading to discontinuation (–0.10: –0.17 to –0.03), any grade 4 AE (–0.07: –0.12 to –0.01), and any grade of hyperglycaemia (–0.43: –0.50 to –0.35), weight decreased (–0.24: –0.30 to –0.18), alopecia (–0.16: –0.22 to –0.11), and stomatitis (–0.08: –0.15 to –0.01), and an increased risk of any grade diarrhoea (0.09: –0.00 to 0.19) versus alpelisib-fulvestrant.

The study concluded that for patients with HR-positive, HER2-negative, PIK3CA-altered aBC, capivasertib-fulvestrant has numerically improved PFS and a high probability of being more efficacious than alpelisib-fulvestrant, along with an overall more favorable safety profile. Results are exploratory and subject to limitations.

The study was sponsored by Novartis Pharmaceuticals & AstraZeneca.

Source: https://www.ispor.org/heor-resources/presentations-database/presentation/intl2024-3900/138705

Clinical Trials: https://clinicaltrials.gov/study/NCT02437318

https://clinicaltrials.gov/study/NCT04305496

de Wilt E, Hettle R, Liljas B, (2024). “Indirect Treatment Comparison of Efficacy and Safety of Capivasertib-Fulvestrant Versus Alpelisib-Fulvestrant for PIK3CA-Altered, HR-Positive, Advanced Breast Cancer after Disease Progression Following Endocrine-Based Therapy.” Presented at ISPOR 2024.