Enhertu goes even lower
If AstraZeneca and Daiichi’s Enhertu is to become a $5bn-plus drug, as predicted, it needs to keep expanding into new uses, and the companies gained another indication on Monday with approval in HER2-low and ultralow breast cancer. The FDA nod, based on the second-line Destiny-Breast06 trial, wasn’t a dead cert given a lack of mature overall survival data, and toxicity seen with Enhertu. This will now be an issue for doctors, along with questions over the reliability of HER2 testing. This week’s green light expands on a previous HER2-low thumbs up in a later setting, but the partners are already looking to the future. At the recent JP Morgan healthcare conference Astra highlighted several upcoming readouts that could take the HER2-targeting ADC into first-line and periadjuvant breast cancer. Astra’s JP Morgan presentation noted that earlier use could add 84,000 patients to the 17,000 patients worldwide currently addressed by Enhertu in the second line. Other phase 3 Enhertu trials due to yield data in 2025 include Destiny-Gastric04, in second-line gastric cancer, and Destiny-Lung04, in first-line NSCLC. Enhertu already has full approval in gastric cancer, but its NSCLC green light is only in second-line disease, and only on an accelerated basis.
Upcoming Enhertu readouts
| Trial | Setting | Regimen | Note |
|---|---|---|---|
| Destiny-Breast11 | Neoadjuvant HER2+ve early breast cancer | +/- paclitaxel + Herceptin + Perjeta, vs chemo + paclitaxel + Herceptin + Perjeta | Data due H1 2025 |
| Destiny-Breast05 | Adjuvant HER2+ve early breast cancer (following neoadjuvant therapy) | vs Kadcyla | Data due H2 2025 |
| Destiny-Breast09 | 1st-line HER2+ve metastatic breast cancer | +/- Perjeta, vs chemo + Herceptin + Perjeta | Data due H2 2025 |
| Destiny-Gastric04 | 2nd-line HER2+ve gastric or GEJ cancer | vs Cyramza + paclitaxel | Data due H2 2025 |
| Destiny-Lung04 | 1st-line NSCLC with HER2 exon 19 or 20 mutations | vs cisplatin or carboplatin + Keytruda + pemetrexed | Data due H2 2025 |
Source: OncologyPipeline & AstraZeneca JP Morgan presentation, Jan 2025.
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