NHS Scotland Grants Trastuzumab Deruxtecan Approval for Use in Pretreated HER2+ Metastatic Breast Cancer

The Scottish Medicines Consortium (SMC) has accepted fam-trastuzumab deruxtecan-nxki (Enhertu) as a treatment option for adult patients with HER2-positive unresectable or metastatic breast cancer who have received 1 prior anti–HER2-based therapy.¹

“We are delighted with this decision by the SMC. Scotland is currently developing a new cancer strategy, and we look forward to partnering with the Scottish Government to set a new ambition for cancer. Part of that ambition must be for rapid access to innovate cancer treatments, empowering the SMC to continue making positive decisions for Scottish patients like the one we’ve seen today,” Tom Keith-Roach, president of AstraZeneca UK, stated in a news release.

Previously, the SMC accepted trastuzumab deruxtecan for use in patients with HER2-positive unresectable or metastatic breast cancer who have previously received 2 or more anti–HER2-based therapies.²

The advice is based on findings from the pivotal phase 3 DESTINY-Breast03 trial (NCT03529110), in which trastuzumab deruxtecan led to a 12-month progression-free survival (PFS) rate of 75.8% (95% CI, 69.8%-80.7%) vs 34.1% (95% CI, 27.7%-40.5%) with ado-trastuzumab emtansine (T-DM1; Kadcyla) assessed by blinded independent central review (BICR) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab (Herceptin) and a taxane (HR, 0.28; 95% CI, 0.22-0.37; P < .001).¹

The primary end point of the trial was PFS based on BICR. Secondary end points were overall survival (OS), objective response rate (ORR), duration of response, PFS based on investigator assessment, and safety.

At the second interim analysis for OS, trastuzumab deruxtecan achieved a statistically significant improvement in OS compared with T-DM1 (HR, 0.64; 95% CI, 0.47-0.87; P = .0037). Additionally, the confirmed ORR with trastuzumab deruxtecan was more than double that with T-DM1, at 79.7% (95% CI, 74.3%-84.4%) vs 34.2% (95% CI, 28.5%-40.3%), respectively. In addition, investigator-assessed median PFS was 25.1 months (95% CI, 22.1–not evaluable) with trastuzumab deruxtecan vs 7.2 months (95% CI, 6.8-8.3) with T-DM1 (HR, 0.26; 95% CI, 0.20-0.35; P < .001).

“Today’s SMC acceptance is another significant milestone for the people in Scotland living with HER2-positive metastatic breast cancer,” said Jo Taylor from METUPUK, a charity for people living with metastatic breast cancer. “There is still a significant unmet need within metastatic breast cancer, and earlier treatment options, as well as equity of treatment across the whole of the UK for fair access, are crucial in tackling the disease burden.

Safety was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least one 5.4 mg/kg dose of trastuzumab deruxtecan in the trial.

The most common adverse effects occurring in at least 20% of patients were blood and lymphatic system disorders including decreased platelet count, decreased white blood cell count, and anemia; gastrointestinal disorders including nausea, vomiting, constipation, and diarrhea; and general disorders including fatigue, and headache. Decreased neutrophil count, decreased appetite, weight decrease, and skin and subcutaneous disorders also occurred.

Of the 39 events (15%) of interstitial lung disease (ILD), less than 1% were characterized as Common Terminology Criteria for Adverse Events grade 3 events. No grade 4 or grade 5 ILD or pneumonitis events were determined to be drug related.

In England, trastuzumab deruxtecan was accepted by the National Institute for Health and Care Excellence (NICE) for use within the Cancer Drugs Fund in December 2022 as a treatment option for HER2-positive unresectable or metastatic breast cancer after at least 1 prior anti-HER2 treatment in adults. Trastuzumab deruxtecan has also been accepted in Wales and Northern Ireland in line with the NICE recommendation.

References

1. ENHERTU (trastuzumab deruxtecan) accepted for use within NHS Scotland earlier in the treatment pathway for HER2-positive metastatic breast cancer. News release. Daiichi Sankyo UK Ltd and AstraZeneca UK; April 12, 2023. Accessed April 12, 2023.
2. ENHERTU (trastuzumab deruxtecan) accepted for use within NHS Scotland for the treatment of HER2 positive metastatic breast cancer. News release. Daiichi Sankyo UK Ltd and AstraZeneca UK; January 17, 2022. Accessed April 12, 2023.