T-DXd Fails to Receive Recommendation From NICE for HER2-Low Breast Cancer Treatment

The UK’s National Institute for Health and Care Excellence (NICE) has announced that it will not recommend the use of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) for the treatment of patients with HER2-low breast cancer.¹

NICE stated in its final draft guidance that despite the improvement in overall survival (OS) and progression-free survival (PFS) seen with the antibody-drug conjugate (ADC) vs chemotherapy, it is unlikely to be cost-effective due to the price of the agent.

Findings from the pivotal, phase 3 DESTINY-Breast04 (NCT03734029) trial, which were updated with median follow-up of 32.0 months (95% CI, 31.0-32.8) at the 2023 ESMO Congress, demonstrated a 6.1-month improvement in OS (HR, 0.69; 95% CI, 0.55-0.86) and a 4.6-month improvement in PFS (HR, 0.36; 95% CI, 0.29-0.45) with the ADC in the overall population of patients with HER2-low unresectable or metastatic breast cancer treated with 1 to 2 prior lines of chemotherapy in the metastatic setting.²

The respective 24-month PFS and OS rates with T-DXd were 14.5% (95% CI, 10.8%-18.7%) and 47.3% (95% CI, 41.9%-52.4%) vs 0% and 32.0% (95% CI, 24.8%-39.3%) with chemotherapy. At 36 months, 26.2% (95% CI, 20.8%-31.9%) of patients were alive on T-DXd vs 16.3% (95% CI, 10.3%-23.6%) on chemotherapy.²

In the UK, 100 mg of the drug, which is used to create a concentrated solution for infusion, costs approximately £1,455 ($1,852). However, the National Health Service receives the drug from Daiichi Sankyo at an unknown discount. Despite this, NICE contended that the drug’s overall benefits are unlikely to be cost-effective.¹

“Despite accounting for the condition’s severity … and accounting for innovation and uncaptured benefits, the most likely cost-effectiveness estimate [is] above the upper end of the range NICE considers an acceptable use of NHS resources,” the draft document read. “So, trastuzumab deruxtecan is not recommended.”

The ADC received its first indication in the UK in February 2021 for the treatment of patients with unresectable or metastatic HER2-positive breast cancer who have received at least 2 prior lines of HER2-directed therapy.^1,3 In August 2022, the United Kingdom’s Medicines and Healthcare Products Regulatory Agency extended the conditional marketing authorization for T-DXd to patients with unresectable or metastatic HER2-positive breast cancer who have received at least 1 prior HER2-based regimen.⁴

Although the drug will not be available within the National Health Service (NHS) for the HER2-low population, the agent has received the green light for use in this population in other countries including the United States, European Union, Japan, and China.^5,6,7,8

Following the announcement, the patient group Breast Cancer Now has created an online emergency petition calling on the agencies, Daiichi Sankyo and AstraZeneca to “do everything possible to find a solution that makes [T-DXd] available on the NHS.”¹

In a statement, Baroness Delyth Morgan, chief executive at Breast Cancer Now called on NHS England, NICE, Daiichi Sankyo, and AstraZeneca to “come back to the table” and find a solution that “puts women with secondary breast cancer first.”

References

1. UK’s NICE rejects AstraZeneca, Daiichi Sankyo’s Enhertu for NHS use. News release. BioSpace. March 6, 2024. Accessed March 6, 2024. https://www.biospace.com/article/uk-s-nice-rejects-astrazeneca-daiichi-sankyo-s-enhertu-for-nhs-use/?keywords=cancer
2. Modi S, Jacot W, Iwata H, et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): updated survival results of the randomized, phase III DESTINY-Breast04 study. Ann Oncol. 2023;34(suppl 2):S334-S335. doi:10.1016/j.annonc.2023.09.553
3. Enhertu approved in the EU for the treatment of HER2-positive metastatic breast cancer. News release. AstraZeneca. January 20, 2021. Accessed March 6, 2024. https://www.astrazeneca.com/media-centre/press-releases/2021/enhertu-approved-in-the-eu-for-breast-cancer.html#
4. Enhertu (trastuzumab deruxtecan) authorised by the MHRA for the treatment of HER2-positive unresectable or metastatic breast cancer treated with one or more prior anti-HER2-based regimens. News release. Daiichi Sankyo UK, Limited and AstraZeneca UK. August 17, 2022. Accessed March 6, 2024.
5. FDA approves fam-trastuzumab deruxtecan-nxki for HER2-low breast cancer. FDA. August 5, 2022. Accessed March 6, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fam-trastuzumab-deruxtecan-nxki-her2-low-breast-cancer#:~:text=low%20breast%20cancer-,FDA%20approves%20fam%2Dtrastuzumab%20deruxtecan%2Dnxki,for%20HER2%2Dlow%20breast%20cancer&text=On%20August%205%2C%202022%2C%20the,%2C%20Daiichi%20Sankyo%2C%20Inc
6. Enhertu approved in the EU as the first HER2 directed therapy for patients with HER2 low metastatic breast cancer. News release. Daiichi Sankyo. January 26, 2023. Accessed March 6, 2024. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202301/20230126_E.pdf
7. Enhertu® approved in Japan as the first HER2 directed therapy for patients with HER2 low metastatic breast cancer. News release. Daiichi Sankyo. March 27, 2023. Accessed March 6, 2024. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202303/20230327_E.pdf
8. Enhertu approved in China as the first HER2-directed therapy for patients with HER2-low metastatic breast cancer. News release. AstraZeneca. July 12, 2023. Accessed March 6, 2024. https://www.astrazeneca.com/media-centre/press-releases/2023/enhertu-approved-in-china-as-the-first-her2-directed-therapy-for-patients-with-her2-low-metastatic-breast-cancer.html