Enhertu completes its front-line march
Astra and Daiichi bag FDA approval based on Destiny-Breast09.
Astra and Daiichi bag FDA approval based on Destiny-Breast09.
After more than a decade without changes, the first-line treatment landscape for HER2-positive metastatic breast cancer is shifting. AstraZeneca and Daiichi’s Enhertu has become the first new front-line therapy here in 13 years, after securing FDA approval in combination with Roche's Perjeta, well ahead of its 23 January 2026 PDUFA date.
The decision was backed by results from the phase 3 Destiny-Breast09 trial, unveiled at ASCO, which showed the combo reduced the risk of disease progression or death by 44% versus Perjeta, Herceptin and chemo.
This latest nod follows the HER2-targeting ADC's first approval, on an accelerated basis, in 2019 for HER2-positive disease following two or more prior anti-HER2-based regimens, based on Destiny-Breast01. In 2022, this was converted to full approval, and also expanded to include second-line HER2-positive disease, based on Destiny-Breast03. Later, approvals came in HER2-low and ultralow relapsed settings.
Even earlier
AstraZeneca and Daiichi are now looking to push the drug to even earlier lines, with the adjuvant Destiny-Breast05 and the neoadjuvant Destiny-Breast11 presented at ESMO.
Astra has predicted that Enhertu could make peak sales of over $5bn; first-line is its biggest approved use so far, with around 135,000 addressable patients, according to the company, although this is dwarfed by the approximately 540,000 perioperative patients.
Next in the space could be Pfizer’s Tukysa, which recently showed promise in the first-line maintenance setting. At SABCS, the company reported that in the Her2climb-05 trial, the HER2 inhibitor combined with Herceptin and Perjeta reduced the risk of progression or death by 36% compared with Herceptin and Perjeta alone.
Pfizer has yet to disclose filing plans, but Tukysa could take on Pfizer’s own CDK4/6 inhibitor Ibrance, which showed a similar relative benefit when added to standard of care in the Patina study. However, despite Patina results being presented at last year's SABCS meeting, the company told ApexOnco it was in "ongoing discussions with regulatory authorities" about that trial.
Recent Enhertu readouts in breast cancer
| Trial | Setting | Regimen | Note |
|---|---|---|---|
| Destiny-Breast09 | 1st-line HER2+ve metastatic breast cancer | + Perjeta, vs Herceptin + Perjeta + chemo* | FDA approved Dec 2025, based on 44% reduction in risk of disease progression/death |
| Destiny-Breast05 | Adjuvant HER2+ve early breast cancer (following neoadjuvant therapy) | vs Kadcyla | Data at ESMO 2025: 53% reduction in risk of disease recurrence/death; filing not yet disclosed |
| Destiny-Breast11 | Neoadjuvant HER2+ve early breast cancer | + paclitaxel + Herceptin + Perjeta, vs chemo + paclitaxel + Herceptin + Perjeta | Data at ESMO 2025: pathologic CR 67% vs 53%; PDUFA date 18 May 2026 |
Note: *Also included Enhertu monotherapy arm, data due H2 2026 . Source: OncologyPipeline.
11
