Pfizer's Tukysa greenlit for earlier use in breast cancer

Pfizer has claimed FDA approval for front-line maintenance use of its oral HER2 inhibitor Tukysa in breast cancer, an indication it hopes will unlock the product's growth potential.

The US regulator has cleared Tukysa (tucatinib) – in combination with anti-HER2 antibodies trastuzumab and pertuzumab – for maintenance treatment of locally advanced or metastatic HER2-positive breast cancer that cannot be treated with surgery, after an initial course of induction treatment.

Pfizer acquired Tukysa as part of its $43 billion takeover of Seagen in 2023, three years after the drug first reached the US market as a second-line or later therapy for HER2-positive advanced breast cancer, and on the heels of a second approval in previously-treated, HER2-positive colorectal cancer.

Once billed as a future blockbuster, Tukysa has underperformed commercially, mainly because of strong competition in the breast cancer market from AstraZeneca and Daiichi Sankyo's fast-growing anti-HER2 antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan).

While an extending list of indications has seen Enhertu reach blockbuster status, with sales approaching $3 billion in the first half of this year, Tukysa made $234 million in the same period, only slightly up from the same period of 2025.

It has lagged behind other assets in the Seagen portfolio – namely Padcev (enfortumab vedotin) for bladder cancer and Adcetris (brentuximab vedotin) for blood cancers – which made $967 million and $472 million, respectively, in the first half.

Pfizer is hoping for a new lease of life for Tukysa with the new maintenance approval, noting that it offers "a new chemotherapy-free maintenance treatment option that may help further delay disease progression."

Its filing to extend the label of Tukysa was based on data from the HER2CLIMB-05 study, revealed at the SABCS conference last December, which showed that the combination regimen reduced the risk of disease progression or death by 36% compared to trastuzumab and pertuzumab alone when given to patients after initial induction chemotherapy.

"The treatment landscape for HER2+ metastatic breast cancer has evolved dramatically over the past decade, but many patients still experience disease progression despite initial benefit from therapy," commented Erika Hamilton of the Sarah Cannon Research Institute (SCRI), who was principal investigator for the study.

"The HER2CLIMB-05 findings support Tukysa plus trastuzumab and pertuzumab as a chemotherapy-free maintenance strategy that allows us to target HER2-positive tumours from multiple angles and can help prolong disease control."

The data prompted a sizeable uprating of analysts' peak sales projections for Tukysa, which had been around $500 million at the end of the decade, prior to the HERCLIMB-05 results, but are now in the region of $1.5 billion.

Pfizer is also looking at moving Tukysa into earlier-stage breast cancer with an adjuvant study in high-risk, HER2-positive breast cancer, CompassHER2 RD, which is due to read out in 2028.