ESMO Congress 2026

Ipatasertib is an oral AKT inhibitor whose established clinical evidence to date has not been in HR+/HER2- breast cancer: the LOTUS phase 2 trial explored the combination with paclitaxel in first-line triple-negative breast cancer ^[1], and reviews noted that PI3K/AKT pathway aberrations are common across breast cancer subtypes, making AKT a viable target ^[2][6]; in metastatic castration-resistant prostate cancer, a phase Ib/II study with abiraterone showed prolonged rPFS with greater benefit in PTEN-loss tumours ^[4], and the phase 3 IPATential150 with abiraterone has been published ^[3]; per reviews at the time, phase III trials of the two AKT inhibitors ipatasertib and capivasertib were under way in HR+ and triple-negative breast cancer ^[5][6]. In other words, mature data for this drug in the endocrine-resistant, CDK4/6 inhibitor-pretreated HR+/HER2- population were previously lacking.

The ESMO26 oral presentation delivered exactly this readout: CCTG MA.40/FINER compared ipatasertib + fulvestrant versus placebo + fulvestrant in HR+/HER2- metastatic breast cancer after a CDK4/6 inhibitor + AI, with stratification by cfDNA before treatment, presented by Andrew Redfern. The PFS benefit was maintained: 5.3 vs 1.9 months in the ITT population, HR 0.68, and HR 0.55 in the AKT pathway-altered cohort, with 45% of patients pathway-altered. However, there was no OS benefit: ITT OS was 26.68 vs 25.76 months, HR 0.97 (p=0.83), and HR 0.88 in the AKT pathway-altered subgroup, also not significant. Field posts also noted longer time to subsequent systemic therapy or death; on safety, diarrhea occurred in 93% of patients with fairly high rates of grade 2/3.

The site news independently covered the same result, listing it among four HR+/HER2- advanced breast cancer LBAs at ESMO 2026 (spanning endocrine combinations, ADCs and immunotherapy), consistent with the field posts: the PFS improvement with ipatasertib plus fulvestrant did not translate into an OS benefit; the news widened the lens to the broader treatment landscape of this tumour type but added no specific numbers beyond the field posts.

In terms of advancing existing knowledge, FINER solidified the PFS benefit of AKT inhibition in the post-CDK4/6i HR+/HER2- population at both the ITT and AKT pathway-altered levels, echoing the pathway-inhibition sensitivity suggested by earlier studies such as LOTUS ^[1][2]; yet the absence of an OS benefit perpetuates this class's long-standing problem, with field commentators likewise lamenting that AKT inhibitors struggle to translate into OS gains. Limitations are equally clear: both OS HRs hover around 1, the subgroup HR 0.88 was not significant, the 93% diarrhea rate and high grade 2/3 toxicity pose tolerability challenges for the combination, and details of the oral presentation remain to be disclosed.