UK’s MHRA Extends Conditional Marketing Authorization for Trastuzumab Deruxtecan to Select HER2+ Metastatic Breast Cancer

The United Kingdom Medicines and Healthcare Products Regulatory Agency has extended the conditional marketing authorization of fam-trastuzumab deruxtecan-nxki for single-agent use in adult patients in Great Britain who have HER2-positive unresectable or metastatic breast cancer and have received 1 or more prior HER2-based regimens.

The United Kingdom (UK)’s Medicines and Healthcare Products Regulatory Agency (MHRA) has extended the conditional marketing authorization of fam-trastuzumab deruxtecan-nxki (Enhertu) for single-agent use in adult patients in Great Britain who have HER2-positive unresectable or metastatic breast cancer and have received 1 or more prior HER2-based regimens.1

The regulatory decision is supported by findings from the phase 3 DESTINY-Breast03 trial (NCT03529110), which showed that treatment with trastuzumab deruxtecan resulted in a 72% reduction in the relative risk of disease progression or death vs ado-trastuzumab emtansine (T-DM1; Kadcyla) in those with HER2-positive, unresectable and/or metastatic breast cancer who received prior trastuzumab (Herceptin) and a taxane (HR, 0.28; 95% CI, 0.22-0.37; P < .001).2

“Today’s decision from the MHRA is significant news for patients with HER2-positive metastatic breast cancer. The DESTINY-Breast03 trial results demonstrated a substantial improvement with trastuzumab deruxtecan compared with the previous standards,” Professor Peter Schmid, FRCP, MD, PhD, of Barts Cancer Institute, stated in a press release. “The license extension is a significant step forward in ensuring patients in the UK have access to trastuzumab deruxtecan earlier in their treatment.”

The multicenter, open-label, phase 3 trial enrolled patients with HER2-positive, unresectable or metastatic breast cancer that had progressed during or following treatment with trastuzumab or a taxane in the context of advanced or metastatic disease, or that had progressed within 6 months following neoadjuvant or adjuvant treatment involving trastuzumab or a taxane.

Study participants were randomly assigned 1:1 to intravenous (IV) trastuzumab deruxtecan given at 5.4 mg/kg every 3 weeks (n = 261) or IV trastuzumab emtansine given at 3.6 mg/kg every 3 weeks (n = 263). Key stratification factors included hormone receptor status (positive vs negative), prior treatment with pertuzumab (Perjeta; yes vs no), and history of visceral disease (yes vs no).

The primary end point of the trial was progression-free survival (PFS) per blinded independent central review (BICR), and overall survival served as a key secondary end point. Other secondary end points comprised overall response rate (ORR) per BICR, investigator-assessed PFS, and safety.

Demographic and baseline disease characteristics were noted to be comparable between the 2 treatment arms and to be largely representative of the overall population of patients with HER2-positive disease.

Notably, 49.8% of patients in the investigative arm vs 46.8% of those in the control arm received 1 prior line of therapy in the context of metastatic disease, and 62.1% and 60.1% of patients, respectively, received prior pertuzumab. Moreover, 23.8% of those who received trastuzumab deruxtecan had stable brain metastases vs 19.8% of those who were given trastuzumab emtansine.

Additional data from the trial published in the New England Journal of Medicine showed that the median PFS had not yet been reached in the investigative arm vs 6.8 months (95% CI, 5.6-8.2) in the control arm. At 12 months, the percentages of patients alive and without progressive disease per BICR assessment in the investigative and control arms were 75.8% (95% CI, 69.8%-80.7%) and 34.1% (95% CI, 27.7%-40.5%), respectively.

The investigator-assessed median PFS was 25.1 months (95% CI, 22.1–not estimable) with trastuzumab deruxtecan vs 7.2 months (95% CI, 6.8-8.3) with trastuzumab emtansine (HR, 0.26; 95% CI, 0.20-0.35; P < .001).

Moreover, trastuzumab deruxtecan elicited an ORR of 79.7% (95% CI, 74.3%-84.4%) vs 34.2% (95% CI, 28.5%-40.3%) with trastuzumab emtansine. In the investigative and control arms, the complete response rates achieved were 16.1% and 8.7%, respectively.

A total of 257 patients who received at least 1 dose of trastuzumab deruxtecan in DESTINY-Breast03 were evaluated for safety. The most common toxicities reported with the agent, occurring in at least 20% of patients, included laboratory abnormalities, nausea, decreased white blood cell count, decreased neutrophil count, increased aspartate and alanine aminotransferase, decreased hemoglobin, decreased lymphocyte count, decreased platelet count, fatigue, and vomiting, among others.

“Today’s MHRA announcement signals a new chapter for trastuzumab deruxtecan, offering another treatment option for patients with HER2-positive metastatic breast cancer earlier in the treatment pathway,” Arun Kishna, head of oncology at AstraZeneca UK, stated in a press release. “The decision not only validates our investment in further evaluating HER2-targetable cancers but also reinforces our commitment to the breast cancer community and continued alignment to the National Health Service Long-Term Plan for Cancer. Our focus now is to work with National Institute for Health and Care Excellence to ensure reimbursement of trastuzumab deruxtecan.”

References

  1. 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 August 18, 2022.
  2. Cortés J, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386(12):1143-1154. doi:10.1056/NEJMoa2115022