Ibrance cleared in US for 'double-positive' breast cancer

Pfizer's Ibrance has become the first CDK4/6 inhibitor to be approved by the FDA for a challenging subtype of breast cancer that is often resistant to current treatment options.

Ibrance (palbociclib) has been cleared for hormone receptor (HR)-positive, HER2-positive breast cancer, sometimes referred to as 'double-positive' or 'triple-positive', as two types of HR (oestrogen and progesterone) are generally expressed on the tumour cells.

It accounts for around 10% of all breast cancer cases, and is typically treated using a combination of HER2-targeted drugs, hormone therapies, and chemotherapy. Ibrance is the first drug in the CDK4/6 inhibitor class to be tested in this subtype in pivotal trials, according to Pfizer.

The green light follows the PATINA trial – reported at the SABC cancer congress in 2024 and published in the New England Journal of Medicine in January – which enrolled patients with advanced double-positive breast cancer with no signs of disease progression after induction therapy with HER2 drugs and chemo. Patients in the study receive maintenance HER2-targeted and endocrine therapies, with or without Ibrance.

It demonstrated a 24% reduction in the risk of disease progression or death with the addition of Ibrance, with a median progression-free survival (PFS) of 44.4 months with the drug versus 29.1 months in the control group, with a trade-off of more toxic effects, mainly neutropenia.

"Resistance to dual anti-HER2 and endocrine therapy remains a central clinical challenge for patients with HR+, HER2+ metastatic breast cancer – even after an excellent response to initial treatment," said Otto Metzger, MD, principal investigator of the PATINA trial for Alliance Foundation Trials (AFT) and a medical oncologist at the Dana-Farber Cancer Institute in the US.

He added that the Ibrance approval gives oncologists "a new treatment option for patients and provides clinicians with another tool to help manage a complex and challenging disease."

The new approval comes as $4 billion-plus blockbuster Ibrance is approaching the end of its patent life in the US in the next few years, and as it faces increasing competition in the CDK6/6 inhibitor category from other drugs like Novartis' Kisqali (ribociclib) and Eli Lilly's Verzenios (abemaciclib).

As the first drug in the class for double-positive tumours, Ibrance now has a niche free of its rivals, as Pfizer works to bring a new-generation candidate, CDK4 inhibitor atirmociclib, through clinical development.

Trodelvy cleared for triple-negative patients

There has also been good news from the FDA for patients with triple-negative breast cancer, after Gilead Sciences' TROP2-directed antibody-drug conjugate (ADC) Trodelvy (sacituzumab govitecan) was given the go-ahead as a first-line monotherapy for patients ineligible for PD-1/PD-L1 inhibitor immunotherapy – almost immediately after the same indication was cleared in the EU – based on the ASCENT-03 trial.

In the US, Trodelvy will compete with AstraZeneca and Daiichi Sankyo's rival TROP2 ADC Datroway (datopotamab deruxtecan), which was approved for the same indication last month.

At the same time, however, the FDA also approved Trodelvy for first-line use in combination with MSD's PD-1 inhibitor Keytruda (pembrolizumab) as a frontline therapy for advanced, PD-L1-positive TNBC on the back of the ASCENT-04 trial, making it the only ADC approved by the FDA for use in patients regardless of their PD-L1 status.