breast cancer

Enhertu is poised to dominate first-line HER2+ breast cancer

Equinox Group’s analysis of the Enhertu + Perjeta combination in first-line HER2+ breast cancer predicts a peak-year patient share of 46% in that setting. Our finding is based on initial results from the Destiny-Breast09[1] trial and the expected competitive environment. FDA approval in first-line is likely by the end of 2025[2].

The core of our analysis compares the net clinical improvement of the Enhertu regimen vs. the current standard of care, Perjeta + Herceptin + paclitaxel. Using our rigorous, data-driven methodology, we find that the Enhertu regimen reduces medical need by 14.6%.

History shows that drugs with a 10% or greater reduction in need typically go on to dominate their segment. Enhertu’s improvement in this population is similar to Tagrisso’s advantage in first-line EGFR+ NSCLC.

The graphic quantifies that net clinical improvement, and shows the contribution of each clinical attribute. The biggest driver is efficacy, primarily progression-free survival (40.7 months for the Enhertu regimen vs. 26.9 months for the SOC). Because the median overall survival data is not yet mature, we have made a conservative assumption about that value for Enhertu. Moreover, the Enhertu regimen spares patients paclitaxel, greatly reducing the frequency of neutropenia and offering a cleaner side effect profile. While the Enhertu regimen costs more, that modest disadvantage is overwhelmed by the clinical benefits.  

[1] Tolaney et al. 2025

[2] Daiichi Sankyo Press Release, July 2025

Enhertu: A New Leader in Later-Line Breast Cancer

Conclusion: Enhertu achieves an impressive clinical innovation score for its substantial efficacy improvements over the current SOC (trastuzumab + capecitabine) for adults with HER2+ metastatic breast cancer who have failed multiple prior therapies.

Enhertu (trastuzumab deruxtecan, Daiichi-Sankyo and AstraZeneca) was approved in December 2019 for HER2+ unresectable or metastatic breast cancer patients who have received multiple prior anti-HER2 treatments. It boasts a significant increase in progression-free survival compared to the current standard of care (SOC), trastuzumab + capecitabine (16.4 vs. 5.6 months), as well as a notable improvement in overall response rate (60.9% vs. 22.8%). While survival data is not yet mature, even the most conservative of estimates sees Enhertu winning the day for HER2+ patients eligible for a third or later line of treatment.

The waterfall chart below shows that Enhertu’s improvements in efficacy far outweigh its higher cost and slightly worse side effect profile when compared to the current SOC. The jump in efficacy, as well as its trickle-down effect on mortality and morbidity, deliver a strong clinical innovation score of 26%.

drivers correct.JPG

We expect Enhertu to dominate treatment in this setting within two years. Analysts’ estimates of peak sales around $2.5 billion are reasonable.