ESMO Congress 2026

Ipatasertib is an oral ATP-competitive AKT inhibitor whose prior randomized evidence sits in two tumor types: the phase 2 LOTUS trial evaluated it with paclitaxel as first-line therapy for metastatic triple-negative breast cancer ^[1]; in metastatic castration-resistant prostate cancer, a randomized phase 2 study showed ipatasertib plus abiraterone prolonged rPFS versus placebo plus abiraterone, with a larger prolongation in PTEN-loss tumors ^[4], leading to the phase 3 IPATential150 ^[3]. Reviews list ipatasertib and capivasertib as the two AKT inhibitors in phase III development ^[5], with phase III trials in HR+ and triple-negative breast cancer underway and predictive biomarkers flagged as an unmet need ^[6].

The Proffered Paper reported at this meeting is FINER (CCTG MA.40): in endocrine-resistant HR+/HER2- metastatic breast cancer after CDK4/6 inhibitor + AI, comparing fulvestrant with or without ipatasertib, with cfDNA-based stratification before treatment. The readout is improved PFS without OS benefit: ITT PFS 5.3 vs 1.9 months (HR 0.68), and HR 0.55 in the AKT pathway-altered cohort (45% of patients); for OS, a post labeled 'Updated OS' gave ITT HR 0.97 (p=0.83) and HR 0.88 in AKT pathway-altered patients, while an earlier post cited OS of 26.7 vs 25.8 months, HR 1.14 (also 1.14 in the AKT-mutant cohort) — official data should prevail. Longer time to subsequent systemic therapy or death was also reported; diarrhea occurred in 93% with fairly high G2/3 rates. Sample size and trial phase were not disclosed.

Relative to prior knowledge, FINER's step forward is bringing AKT inhibition into the post-CDK4/6 inhibitor HR+/HER2- endocrine-resistant setting with randomized PFS benefit, and a larger effect in the AKT pathway-altered cohort (HR 0.55 vs 0.68), consistent with the biomarker-selection direction emphasized in the literature ^[6]. But PFS did not translate into OS — no OS benefit in ITT or AKT pathway-altered cohorts, and the absolute ITT median PFS difference is modest (5.3 vs 1.9 months); one on-site post commented that this class 'keeps failing to deliver OS gains.'

Limitations: all figures come from conference posts; one physician explicitly said the presentation details are awaited to understand why the PFS benefit did not translate into OS; the OS numbers differ across posts; 93% diarrhea with fairly high G2/3 rates point to a tolerability burden; and the 45% pathway-altered proportion and cfDNA stratification details await confirmation from formal data.