LBA5 - Capivasertib (C) + fulvestrant (F) for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2– advanced breast cancer (ABC): Phase III CAPItello-291 trial Chinese cohort

Background

The global phase 3 CAPItello-291 trial of AI-resistant, HR+/HER2– ABC, C (a potent pan-AKT inhibitor) + F showed significant, clinically meaningful improvement in the dual primary endpoints of PFS in the overall and PIK3CA/AKT1/PTEN-altered population vs placebo (P) + F (Turner, NEJM 2023). Here we report outcomes from pts from the global population (n=24) plus an extended Chinese cohort.

Methods

Pts were randomised 1:1 to F (500 mg IM on days 1 and 15 of cycle 1, and day 1 of each subsequent 28-day cycle) with P or C (400 mg BID; 4 days on, 3 days off) using the same entry criteria as the global study. PIK3CA, AKT1, or PTEN alterations in pts from mainland China were determined using NGS in tumour tissue (OncoScreen Plus assay, Burning Rock Biotech). PFS was investigator-assessed.

Results

134 pts from mainland China (n=118) and NMPA-certified sites in Taiwan (n=16) (C + F n=71, P + F n=63) were enrolled; 34.3% had PIK3CA/AKT1/PTEN-altered tumours. Baseline characteristics were broadly comparable in the Chinese cohort vs Global population, including pre/perimenopausal status (29.9% vs 21.8%) and liver metastases (45.5% vs 43.2%). Fewer pts had ECOG PS 0 (49.3% vs 65.7%) or had a CDK4/6 inhibitor (38.8% vs 70.1%); more pts had prior chemotherapy for ABC (29.9% vs 18.2%). Consistent with the Global population, PFS benefit in the Chinese cohort was observed in the overall population (median PFS 6.9 mo with C + F vs 2.8 mo with P + F; HR 0.51, 95% CI: 0.34–0.76) and in the PIK3CA/AKT1/PTEN-altered population (5.7 vs 1.9 mo; HR 0.41, 95% CI: 0.19–0.85). PFS benefit in subgroups, including by PIK3CA/AKT1/PTEN alteration status, and will be presented. The most frequent AEs with C + F were diarrhoea (60.6% vs 11.3% P + F) and hyperglycaemia (57.7% vs 17.7%); the most frequent grade ≥3 AEs were rash maculopapular (8.5% vs 0%), rash and diarrhoea (both 7.0% vs 0%); grade ≥3 hyperglycaemia was 1.4% vs 0%. AEs leading to C/F discontinuation were reported in 11.3% for C + F vs 3.2% for P + F.

Conclusions

Similar to the Global population, the benefit–risk profile of C + F in the Chinese cohort appears favourable; no new safety concerns with C + F were identified.

Clinical trial identification

NCT04305496.

Editorial acknowledgement

Medical writing support was provided by Suzanne Patel, Ph.D., from BOLDSCIENCE Inc.

Legal entity responsible for the study

Capivasertib was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).

Funding

AstraZeneca.

Disclosure

Y. Lu: Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, MSD, Roche, Pfizer, AstraZeneca, Eisai, Daiichi Sankyo, Gilead; Financial Interests, Personal, Invited Speaker: Novartis, Eli Lilly, MSD, Roche, Pfizer, AstraZeneca, Eisai, Daiichi Sankyo, Gilead; Financial Interests, Institutional, Local PI: Novartis, Roche, Pfizer, MSD, Eli Lily, Eisai, AstraZeneca, Gilead, Jellox; Non-Financial Interests, Personal, Leadership Role, Chair or co-chair of steering committee of clinical trials: Novartis; Non-Financial Interests, Personal, Advisory Role: AstraZeneca. E. Fan, L. Jiang, X. Zeng: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. N. Turner: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Novartis, Pfizer, Roche/Genentech, GlaxoSmithKline, Zentalis pharmaceuticals, Repare therapeutics, GlaxoSmithKline, Relay therapeutics, Gilead, Inivata, Guardant, Exact Sciences; Financial Interests, Institutional, Funding: AstraZeneca, Pfizer, Roche/Genentech, Merck Sharpe and Dohme, Invitae, Inivata, Personalis, Natera; Financial Interests, Institutional, Other, provision of materials: BioRad; Financial Interests, Institutional, Other, Provision of assays: Guardant Health. All other authors have declared no conflicts of interest.