Roche, hoping to carve out a standard-of-care spot for its PI3K inhibitor Itovebi, now has another leg to stand on with new evidence that shows the drug can extend the lives of certain patients with breast cancer.
Adding Itovebi to Ibrance and Faslodex slashed 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 data, to be presented at the American Society of Clinical Oncology’s (ASCO's) annual meeting, come from Roche’s pivotal phase 3 INAVO120 trial.
In the 325-patient study, Roche’s Itovebi triplet combination kept patients alive for a median of 34 months compared to 27 months for those who took a placebo along with Ibrance and Faslodex.
Itovebi won its FDA approval in the indication based on data from INAVO120 in late 2024, although full overall survival data were immature at the time.
A 33% improvement in overall survival marks a key milestone for the P13KCA-targeting arena, in which no drug before had delivered a statistically significant survival benefit, head of oncology and hematology global product development at Roche’s Genentech, Charlie Fuchs, M.D., explained in an interview with Fierce Pharma.
A 2020 final analysis of Itovebi’s rival PI3K inhibitor, Novartis’ Piqray, for example, failed to show statistical significance in the overall survival measure for patients with PIK3CA-mutated breast cancer.
Roche has long claimed that its offering has best-in-class capabilities due to its specificity in targeting, but the latest data drop drives that point home as the “proof in the pudding,” Fuchs said.
Adding to the pudding, the final overall survival results allow Roche to recalculate Itovebi’s previously reported progression-free survival findings. Previously, the therapy was said to have kept patients alive longer without their disease getting worse for a median of 15 months. That number is now up to 17.2 months, versus the unchanged 7.3 months observed in the placebo group.
On the safety side, serious side effects were seen in both the placebo and treatment groups, with 90.7% of patients who took Itovebi experiencing a grade 3 or 4 adverse event compared to 84.7% in the placebo arm. Hyperglycemia, or high blood sugar, was particularly prevalent in the Itovebi group and impacted 63.4% of patients, versus 13.5% of those on placebo.
Hyperglycemia is a known concern for Piqray as well, but, considering that Roche has a “considerable amount of data” proving the condition isn’t a main driver of treatment discontinuation and doesn’t occur in every Itovebi patient, Fuchs thinks the safety signal is “manageable.” In INAVO120, 6.8% of patients ended treatment due to side effects, as did 0.6% in the placebo arm.
HR-positive, HER2-negative breast cancer is already the most common subtype of breast cancer, comprising 70% of the breast cancers in the U.S., according to ASCO. About 40% of that population has a mutation in the PIK3CA gene, which is often linked to a poor prognosis.
The Itovebi results serve to highlight the importance of genomic testing at the time of diagnosis, so those with the mutations can be quickly identified, ASCO breast cancer expert Jane Lowe Meisel, M.D., pointed out in an ASCO release.
Given the large market it could harness, Roche is confident in Itovebi’s blockbuster potential, as the company’s pharma head Teresa Graham has put its peak sales estimate at 2 billion Swiss francs ($2.3 billion). Over the drug’s first full quarter on the market, it picked up 14 million Swiss francs ($16.8 million) in sales.
The company is currently pitting Itovebi against Piqray in a head-to-head study in the second-line setting for patients with advanced or metastatic breast cancer following CDK4/6-endocrine combination therapy.