Trastuzumab Deruxtecan May Effectively Treat CNS-Metastatic HER2+ Breast Cancer While Maintaining QOL

Trastuzumab deruxtecan (Enhertu) maintained quality of life in patients with HER2-positive breast cancer with central nervous system (CNS) metastases, according to a secondary end point analysis of the phase 2 TUXEDO-1 trial (NCT04752059).¹

According to the analysis, the treatment did not substantially impair patients’ neurocognitive, physical, emotional, and social functioning, with global European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 health status scores remaining stable during treatment and demonstrating a slope of –0.13 per follow-up visit (P = .95).

“TUXEDO-1 showed maintained quality of life and neurocognitive function during trastuzumab deruxtecan therapy in HER2-positive breast cancer patients [with brain metastases],” investigators wrote.

In the prospective, open-label, single-arm phase 2 study that was reported in Nature Medicine in 2022, the effects of trastuzumab deruxtecan on 15 patients with newly diagnosed or progressive HER2-positive breast cancer with active CNS metastases were examined. With 12 months of follow-up, the overall intracranial response rate per response assessment in neuro-oncology brain metastases (RANO-BM) criteria was 73.3% (95% CI, 48.1%-89.1%), comprised of 2 complete responses (13.3%) and 9 partial responses (60%); an additional 3 patients (20%) had stable disease. The median progression-free survival was 14 months (95% CI, 11-not reached).²

Global QLQ-C30 scores meanwhile were maintained during treatment in all 4 domains. Per follow-up visit, slopes per follow-up visit were 0.52 for physical functioning (P = .36); –0.79 for cognitive functioning (P = .43); –0.24 for emotional functioning (P = .84); and 0.59 for social functioning (P = .65).

Patients were required to have histologically confirmed disease and radiologically documented metastases to be included, as well as an ECOG score lower than 2. One of the enrolled patients was male; the other 14 were female. The median age of the study population was 69 years (range, 30-76 years) and neurologic symptoms were present in 40% of patients (n = 6) at enrollment. The patient population received a median of 2 (range, 1-5) previous systemic therapies for metastatic breast cancer and 60% of patients (n = 9) had received prior local therapy, either whole brain radiotherapy, stereotactic radiotherapy, or neurosurgery. Ten patients (66.7%) had stage IV disease at primary diagnosis, with the remainder having stage I to III disease.

Patients were administered intravenous trastuzumab deruxtecan at 5.4 mg/kg every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Patients completed EORTC QLQ-C30 questionnaires at cycles 1, 3, and 5, and every 9 weeks thereafter. Final assessments occurred at the first survival follow-up 3 months after the end of treatment. Investigators analyzed changes in quality-of-life scores using linear mixed-effects models.

“Our data support first-line systemic therapy with trastuzumab deruxtecan in patients with active brain metastases,” investigators concluded.

Prior investigations into this treatment have included a subgroup analysis of the DESTINY-Breast01 trial (NCT03248492) which also found trastuzumab deruxtecan to be effective and tolerable in patients with CNS-metastatic breast cancer.³ Nonetheless, more comprehensive research will be needed to support this treatment in this patient population.

References

1. Starzer AM, Berghoff ASS, Furtner J, et al. Quality of life and neurocognitive function in patients with active brain metastases of HER2-positive breast cancer treated with trastuzumab-deruxtecan: secondary endpoint analysis of the prospective single-arm phase II TUXEDO-1 trial. Ann Oncol. 2022;33(suppl 7):281MO. doi:10.1016/j.annonc.2022.07.415
2. Bartsch R, Berghoff AS, Furtner J, et al. Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Nat Med. 2022;28(9):1840-1847. doi:10.1038/s41591-022-01935-8
3. Jerusalem GHM, Park YH, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer with brain metastases: A subgroup analysis of the DESTINY-Breast01 trial. J Clin Oncol. 2021;39(suppl 15):526. doi:10.1200/JCO.2021.39.15_suppl.526