Pfizer is moving up the treatment line once again. The FDA just approved the drugmaker's tyrosine kinase inhibitor Tukysa as a part of a new first-line regimen designed to delay progression of HER2-positive breast cancer.
The approval marks Pfizer’s second HER2 first-line approval in less than four months.
Tukysa won the FDA green light Wednesday for U.S. patients with advanced HER2-positive breast cancer that is not amenable to surgery or has metastasized to distant organs. The current standard of care in theses cases is to lead with induction chemotherapy plus Roche’s two HER2 antibody drugs, Herceptin and Perjeta, and follow with a chemo-free maintenance phase using the two Roche drugs. The FDA approval now includes Tukysa as a beneficial addition to the chemo-free maintenance period.
The FDA based its decision on Pfizer’s HER2Climb-05 phase 3 trial, detailed late last year. In that study, the Tukysa combination met its primary endpoint, reducing the risk of disease progression by 35.9% compared to Herceptin and Perjeta alone. Patients in the treatment arm also went 8.6 months longer without their disease worsening, achieving a median progression free survival of 24.9 months. Data on the trial’s secondary endpoint—overall survival—hasn’t been finalized yet.
The new regimen “allows us to target HER2-positive tumors from multiple angles and can help prolong disease control,” said Erika Hamilton, M.D., the principal investigator of HER2Climb-05 and director of breast cancer research for the Sarah Cannon Research Institute (SCRI).
Safety and tolerability of Tukysa in the trial was largely consistent with previous studies, except for a rise in hepatoxicity which affected 3.9% of patients in the treatment arm. The majority of hepatoxicity cases were asymptomatic and reversed by dose modification or discontinuing the treatment, but one patient did experience a fatal drug-induced liver injury.
HER2 is over expressed—and causes poorer prognosis—in 15% to 20% of breast cancer cases, according to Pfizer’s estimates. The first-line approval will open Tukysa up to a larger patient pool that is earlier in their disease course, meaning they could take the drug for a longer interval.
In June, Pfizer secured a similar frontline maintenance approval for its blockbuster CDK4/6 inhibitor Ibrance. The FDA approved the drug as a maintenance option, in combination with Roche’s Herceptin and with or without Perjeta, for hormone receptor-positive, HER2-positive breast cancer. In the phase 3 Patina trial, this combination extended progression free survival by 15.2 months to a median 44.3 months.
The success of both Tukysa and Ibrance in the maintenance phase have created unexpected competition for AstraZeneca and Daichii Sankyo’s antibody drug conjugate Enhertu, which dominates the HER2 treatment landscape. Enhertu together with Roche’s Perjeta scored a coveted first-line approval in late 2025 after it increased progression free survival by 44%, outperforming the traditional induction regimen with chemotherapy.
The Enhertu regimen is intended to be used until patients progress. But reporting from Fierce earlier this year showed that doctors are tempted to transition off of Enhertu after the induction and switch to maintenance strategies using Tukysa and Ibrance. Neither Pfizer study included Enhertu, and there is, so far, no data on this strategy. But if the strategy gains a foothold, Pfizer’s maintenance strategies could intercept significant Enhertu sales.
Pfizer acquired Tukysa in its $43 billion buyout of Seagen in 2023, three years after its initial approval. Initially, analysts projected peak Tukysa sales at $1.2 billion by 2030.
But sales so far under Pfizer have been somewhat soft, with Tukysa global revenue shrinking from $480 million in 2024 to $463 million in 2025. Some experts have argued the drug’s global performance has not yet lived up to its hefty purchase price. But with the first-line label now in hand, a Tukysa rebound may be in store.