Pfizer's oncology portfolio has produced a second positive phase 3 trial in HER2-positive breast cancer in the span of about a year.
This time, the drug that delivered the positive readout is Tukysa, a HER2-targeted tyrosine kinase inhibitor that Pfizer picked up in its $43 billion acquisition of Seagen.
When used as a first-line maintenance therapy in patients with HER2-positive metastatic breast cancer who’ve responded to standard induction therapy, Tukysa significantly prolonged the time before cancer progression or death compared with placebo, Pfizer said Tuesday. Both Tukysa and placebo were given in combination with the standard maintenance regimen of Roche’s Herceptin and Perjeta.
The statistically significant and clinically meaningful improvement in progression-free survival means that the phase 3 HER2CLIMB-05 trial has met its primary endpoint, Pfizer said.
The positive phase 3 results, “combined with Tukysa’s known safety profile in later-line settings, underscore its potential to play a meaningful role in front-line maintenance, where it may benefit a broader population of patients with HER2+ disease,” Johanna Bendell, M.D., Pfizer’s oncology chief development officer, said in an Oct. 14 release.
Since its FDA approval in 2020, Tukysa has been a key treatment option for second-line HER2+ breast cancer, especially for patients with brain metastases. The positive HER2CLIMB-05 result could potentially move the drug into the earlier, first-line maintenance setting.
The New York pharma said it will discuss the results with regulatory authorities and present the findings at a future medical meeting. The company’s Oct. 14 release did not include any description of overall survival, a key secondary endpoint of HER2CLIMB-05.
The first-line standard-of-care maintenance treatment for patients with HER2-positive breast cancer has remained unchanged since 2012, according to Pfizer.
Meanwhile, changes may be coming for a subset of patients after the cancer research organization Alliance Foundation Trials reported positive results from the phase 3 Patina trial last year. In that study, the addition of Pfizer’s CDK4/6 inhibitor Ibrance to standard anti-HER2 and endocrine therapy significantly reduced the risk of progression or death by 26% in patients with HR-positive, HER2-positive breast cancer who had responded to induction therapy.
A Pfizer spokesperson told Fierce Pharma on Tuesday that conversations with regulatory authorities regarding the Patina results are ongoing.
HR+/HER2+ breast cancer, also known as double-positive breast cancer, constitutes about 10% of all breast cancer cases.
Now, the HER2CLIMB-05 trial holds promise to reshape the broader HER2+ market, especially for those with HR-negative disease, who make up about 70% of breast cancer cases.
The HER2+ breast cancer field is getting more complicated lately, thanks to the rise of antibody-drug conjugates led by AstraZeneca and Daiichi Sankyo’s Enhertu. At the American Society of Clinical Oncology annual meeting in June, the pair trotted out phase 3 data showing a combination of Enhertu and Perjeta significantly improved progression-free survival by 44% compared to the traditional Herceptin-Perjeta-chemo combo in first-line HER2+ breast cancer.
During the discussion session for that trial, ASCO-invited expert Claudine Issacs, M.D., from Georgetown University, suggested that doctors may be tempted to try a sans-Enhertu maintenance treatment based on Patina for the HR+ subset of patients, even though the AZ/Daiichi trial tested the Enhertu-based regimen until disease progression. At that time, Daiichi’s head of global oncology business, Ken Keller, said the company would follow doctors’ treatment patterns closely. Now, depending on its detailed data, HER2CLIMB-05 may invite the same question for HR-negative patients, as well.