Roche’s blockbuster vision for phosphoinositide 3-kinase (PI3K inhibitor) Itovebi (inavolisib) has been dealt a boost after the drug demonstrated further positive overall survival (OS) data in a common subtype of breast cancer.
In combination with Pfizer’s CDK4/6 inhibitor Ibrance (palbociclib) and anti-oestrogen drug Faslodex (fulvestrant), Itovebi reduced the risk of death by 33% in patients with PIK3CA-mutated, HR-positive, HER2-negative locally advanced or metastatic breast cancer that has grown during or after hormone therapy treatment.
The new OS results came from the Phase III INAVO120 study (NCT05646862) evaluating the triple therapy compared to Ibrance and Faslodex alone. Roche published an abstract containing the data ahead of a presentation at the American Society of Clinical Oncology (ASCO) 2025 meeting taking place from 30 May to 3 June in Chicago, Illinois.
Itovebi won US Food and Drug Administration (FDA) approval in this breast cancer indication based on INAVO120’s data late last year, although full analysis of the OS has only been completed by Roche now.
The study, which enrolled 325 patients, saw Roche’s Itovebi combination led to a median OS of 34 months compared to 27 months for those who took a placebo along with Ibrance and Faslodex. The median follow-up was just under three years.
The results consolidate previous data that showed adding Itovebi to the treatment regimen more than doubled progression-free survival (PFS) to 15 months. With the full analysis now available, Roche has updated this to 17.2 months, compared to the 7.3 months in the comparator arm.
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By GlobalDataCoupled with the OS data, the results are a landmark moment in the P13KCA landscape. No other pharma company has developed a candidate that reaches the 33% Itovebi has achieved. For example, rival PI3K inhibitor Piqray developed by Novartis, failed to produce a statistically significant difference in OS in breast cancer patients with a PIK3CA mutation. Piqray is FDA-approved as a second-line therapy option, whereas Itovebi is a first-line treatment.
HR-positive, HER2-negative breast cancer is the most common subtype of breast cancer. About 40% of these patients have a mutation in the PIK3CA gene.
PI3K inhibitors have long been troubled by safety concerns. Roche’s Itovebi is no different, with 90.7% of patients experiencing Grade 3 or 4 adverse events (AEs). However, a high rate was also seen in the placebo/Ibrance/Faslodex arm – 84.7%. Hyperglycaemia was an AE singled out in the analysis, being particularly prevalent in the Itovebi group at 63.4%, versus 13.5% in the other arm.
Backed by previous survival data, Roche has high hopes for Itovebi, forecasting peak sales of $2.3bn. Analysis by GlobalData, which goes up to 2031, has forecast peak sales of $1.4bn.
GlobalData is the parent company of Pharmaceutical Technology and Clinical Trials Arena.
“The INAVO120 trial has identified a targeted treatment regimen that meaningfully improves survival in patients with untreated PIK3CA-mutated hormone receptor-positive metastatic breast cancer – a big step forward for these patients,” said Jane Lowe Meisel, co-director of Breast Medical Oncology at the Winship Cancer Institute of Emory University School of Medicine, and an ASCO Expert in breast cancer.
“This study illustrates the importance of genomic testing at the time of diagnosis of hormone receptor-positive metastatic breast cancer so that patients with PIK3CA mutations who qualify for this approach can be readily identified.”
