Recent improvements in overall and progression-free survival for patients with HER2-positive and estrogen receptor–positive breast cancers have not come at the expense of quality of life or symptom management, according to a pair of studies presented at the European Society for Medical Oncology (ESMO) Breast Cancer Congress 2023.^1,2

In the DESTINY-Breast02 trial, the HER2-targeted antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (T-DXd) improved patient-reported outcomes in HER2-positive metastatic breast cancer.¹ The next-generation oral selective estrogen receptor degrader elacestrant, studied in the EMERALD trial, maintained quality of life in patients with estrogen receptor–positive, HER2-negative advanced breast cancer.²

Tanja Fehm, MD

“The patient-reported outcome data, together with the previous efficacy and safety data from DESTINY-Breast03, support the benefit of trastuzumab deruxtecan in patients with T-DM1–resistant, HER2-positive metastatic breast cancer,” said Tanja Fehm, MD, Director of the Gynecological Clinic, Düsseldorf University Hospital, Germany.

DESTINY-Breast02: T-DXd Improved -Patient-Reported Outcomes

The DESTINY-Breast02 trial, a randomized phase III study, evaluated the use of T-DXd in patients with HER2-positive metastatic breast cancer who had previously been treated with ado-trastuzumab emtansine (T-DM1). The primary endpoint was progression-free survival, and key secondary endpoints included overall survival and health economics and outcomes research.

The trial demonstrated a significant improvement in progression-free survival, with a median of 17.8 months with T-DXd compared with 6.9 months with the physician’s choice treatment. Additionally, T-DXd was associated with a significant overall survival benefit of 12.7 months over the physician’s choice treatment.

The trial also assessed quality of life, physical functioning, and pain symptoms using three validated questionnaires. As Dr. Fehm reported, results showed that global health status and health-related quality of life were maintained during treatment with T-DXd.

“For patients treated with trastuzumab deruxtecan, the median time to definitive deterioration in global health status and overall quality of life was more than twice as long as for those treated with physician’s choice,” said Dr. Fehm. “Similarly, patients had nearly three times longer median time to definitive deterioration in physical functioning and more than three times longer median time to definitive deterioration in pain symptoms.”

The overall safety profile of T-DXd was consistent with the established safety summary. The most common drug-related treatment-emergent adverse events associated with discontinuation of T-DXd were pneumonitis (6.2%) and interstitial lung disease (3.2%), compared with palmar-plantar erythrodysesthesia syndrome (1.5%) in the physician’s choice arm. The most common drug-related treatment-emergent adverse events associated with dose reduction were nausea (5.4%) with T-DXd vs palmar-plantar erythrodysesthesia syndrome (23.6%) with physician’s choice treatment.

EMERALD: Quality of Life Maintained With Elacestrant

The phase III EMERALD trial evaluated elacestrant in patients with estrogen receptor–positive, HER2-negative advanced breast cancer who had previously received endocrine therapy and CDK4/6 inhibitor–based therapy. Patients were randomly assigned to receive either elacestrant or -physician’s choice endocrine therapy.

The primary results of the EMERALD trial showed that elacestrant significantly improved progression-free survival in all patients, especially those harboring ESR1 mutations. In patients who had received prior treatment with CDK4/6 inhibitors and had ESR1 mutations, the median progression-free survival was 8.6 months with elacestrant compared with 2 months with the standard of care.

The EMERALD trial also assessed patient-reported outcomes using three tools: the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire), the patient-reported outcome version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and EQ-5D-5L (European Quality of Life 5 Dimensions 5 Level version).

EORTC QLQ-C30 scores were similar for elacestrant and the standard of care. There were no reported differences across all time points for both functional and symptom scales.

For the PRO-CTCAE, which evaluated the frequency, interference, and severity of various symptoms, no significant differences were observed between the treatment arms. Of note, the incidence of severe nausea and vomiting was higher with the standard of care than with elacestrant.

The EQ-5D-5L, a tool measuring self-rated health status, also showed no significant differences between the two treatment arms in aspects such as mobility, self-care, usual activities, pain discomfort, and anxiety or depression.

Javier Cortés, MD, PhD

“This analysis confirmed that quality of life was maintained between treatment groups in the EMERALD trial,” said lead study author Javier Cortés, MD, PhD, Head of the International Breast Cancer Center, Barcelona. “Together with the previously described statistically significant prolonged progression-free survival and manageable safety profile, these patient-reported outcomes provide additional evidence that oral elacestrant is clinically meaningful in this patient population with limited therapeutic options.” 

DISCLOSURE: Dr. Fehm reported financial relationships with Onkowissen, Medconcept, Novartis, Pfizer, Daiichi Sankyo, Roche, Stemlines, MSD, Pierre Fabre, and AstraZeneca. Dr. Cortés reported financial relationships with Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Eli Lilly, Merck Sharp & Dohme, GSK, LEUKO, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead Sciences, Menarini, Zymeworks, Reveal Genomics, Novartis, Pfizer, Samsung Bioepis, ExpreS2ion Biotechnologies, MedSIR, and Nektar Therapeutics.

REFERENCES

1. Fehm TN, Cottone F, Dunton K, et al: Patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of trastuzumab deruxtecan vs treatment of physician’s choice in patients with HER2-positive metastatic breast cancer. ESMO Breast Cancer Congress 2023. Abstract 186O. Presented May 11, 2023.

2. Cortés J, Bidard FC, Bardia A, et al: EMERALD trial analysis of patient-reported outcomes in patients with ER+/HER2– advanced or metastatic breast cancer comparing oral elacestrant vs standard of care endocrine therapy. ESMO Breast Cancer Congress 2023. Abstract 188O. Presented May 11, 2023.