Pfizer has rolled out detailed trial data suggesting Tukysa could be part of a new first-line treatment to delay the progression of HER2-positive breast cancer.
The current standard of care for the disease includes induction chemotherapy in combination with Roche’s Herceptin and Perjeta, followed by a chemo-free maintenance phase with the two HER2 antibody drugs. Now, Pfizer has shown that adding Tukysa during the maintenance stage can improve patient outcomes.
Specifically, addition of Tukysa to first-line maintenance therapy significantly reduced the risk of progression or death by 35.9%, according to investigator-assessed results from the phase 3 HER2CLIMB-05 trial, which were presented at the San Antonio Breast Cancer Symposium. Patients who received the Pfizer small molecule went 8.6 months longer without tumor progression, reaching 24.9 months at the median.
The drug’s progression-free survival (PFS) benefit was observed across all prespecified treatment subgroups, but its effect appears to be more pronounced in patients who have HR-negative cancer than HR-positive tumors. The magnitude of Tukysa’s PFS improvement was 44.6% and 27.5% in those two subgroups, respectively.
That means Tukysa could likely play a bigger role in the HR-negative subtype of HER2-positive breast cancer in the first-line setting. Previously, in the phase 3 Patina trial, another Pfizer drug, CDK4/6 inhibitor Ibrance, showed a 26% PFS improvement when added to anti-HER2 and endocrine therapy in patients with HR-positive, HER2-positive breast cancer who responded to induction therapy.
Patina’s subjects are likely different from the HR-positive subgroup of HER2CLIMB-05, Erika Hamilton, M.D., from the Sarah Cannon Research Institute and principal investigator of HER2CLIMB-05, said during a press briefing on Dec. 10. In the Tukysa trial, the median PFS for the HR-positive population in the control arm was 18 months, versus 29 months in Patina patients treated with anti-HER2 therapy plus endocrine therapy alone, she pointed out.
“I think this population had a little bit more aggressive disease, a little bit less indolent disease,” Hamilton said.
While the majority of patients were still alive at HER2CLIMB-05's data cutoff of Sept. 5, 2025, Tukysa also showed a promising trend toward prolonging patients’ lives, with a numerical 46.1% reduction in the risk of death. Only 7.8% of patients in the 654-subject trial have died at the time of the analysis.
Investigators described the Tukysa regimen’s safety profile as “manageable,” with diarrhea, nausea and elevated liver enzymes being the most common adverse events, mostly at low grades. All told, 42.3% of patients in the Tukysa arm, versus 24.4% in the control group, experienced treatment-emergent adverse events (TEAEs) at grade 3 or above. There was one TEAE leading to death in both arms.
Pfizer’s HER2CLIMB-05 regimen could further complicate the outlook for AstraZeneca and Daiichi Sankyo’s star HER2-directed antibody-drug conjugate Enhertu in its proposed first-line breast cancer indication.
Recent phase 3 data from the Destiny-Breast09 trial linked the Enhertu-Perjeta combo to a 44% PFS improvement compared with current first-line standard of care. But even though Enhertu is meant to be dosed until progression, questions were raised about doctors potentially switching to the Patina regimen during maintenance for patients with HR-positive tumors, effectively shortening the treatment length—and potential the revenue—of Enhertu. Now, the Tukysa data could raise the same question for HR-negative patients.
“I think the hesitation we’re hearing around [Destiny-Breast09] is really that continuing [Enhertu] indefinitely” means patients could end up taking the HER2 ADC for several years, Hamilton explained.
The HER2CLIMB-05 investigator acknowledged that post-Enhertu maintenance remained a data-free zone. “But I think that even if people are using DB-09, that there’s still going to be a desire for a maintenance strategy, whether that’s Patina or HER2CLIMB-05, as I don’t think that there’s going to be an appetite to continue [Enhertu] indefinitely for patients.”
As Enhertu has become a dominant second-line treatment for HER2-positive breast cancer, Tukysa is mostly used for patients with brain metastases or following progression on Enhertu. In the first nine months of 2025, Tukysa’s sales shrank to $344 million from $351 million during the same period last year.
In HER2CLIMB-05, Tukysa showed similar results with the same 36% PFS improvement in both patients with and without brain metastases at baseline.
Editor's note: This story was updated at 9:10 a.m. ET on Dec. 10 to include comments from Erika Hamilton, M.D., during a press conference.