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Treatment with Enhertu showed favorable outcomes regarding health-related quality of life in patients with HER2-positive breast cancer, regardless of brain metastases.
A phase 3b/4 trial evaluated health-related quality of life in patients with HER2-positive breast cancer, regardless of the presence of brain metastases.
In patients with HER2-positive metastatic breast cancer, health-related quality of life (HRQOL) and neurological function data were relative to the efficacy and safety profile of Enhertu (fam-trastuzumab deruxtecan-nxki) regardless of the presence of stable or active brain metastases, according to findings from a phase 3b/4 trial.
The DESTINY-Breast12 trial, which was presented during the 2024 San Antonio Breast Cancer (SABCS), deterioration-free rates were evaluated. This included cognitive, emotional, physical, role and social functioning abilities.
At the February 8, 2024, data cutoff, the estimated 12-month deterioration-free rate in terms of global health status (GHS)/QOL was 40.3% among 146 evaluable patients with brain metastases. The estimated 12-month deterioration-free rates in terms of cognitive (119 patients), emotional (92 patients), physical (113 patients), role (135 patients) and social functioning (118 patients) were 53.5%, 63.3%, 56.8%, 44.5% and 54.3%, respectively. The estimated 12-month rates regarding pain (113 patients), fatigue (152 patients) and nausea or vomiting (137 patients) were 53.4%, 40.2% and 46.2%, respectively.
Health-related quality of life (HRQOL): physical and mental well-being over time.
Progression-free survival (PFS): time without cancer progression.
Overall response rate (ORR): percentage of patients showing any tumor reduction.
Central nervous system PFS: time without cancer progression in the brain or spinal cord.
Patients with stable brain metastases (87 patients) experienced an estimated 12-month deterioration-free rate of 41% in terms of GHS/QOL. The estimated 12-month deterioration-free rates in terms of cognitive (71 patients), emotional (59 patients), physical (65 patients), role (79 patients and social functioning (72 patients) were 55.3%, 59.3%, 58.4%, 44.3% and 52%, respectively. The estimated 12-month rates regarding pain (67 patients), fatigue (89 patients) and nausea or vomiting (78 patients) were 52.8%, 40.3% and 49.5%, respectively.
Patients with active brain metastases (59 patients) had an estimated 12-month deterioration-free rate of 39.2% in terms of GHS and QOL. The estimated 12-month deterioration-free rates in terms of cognitive (48 patients), emotional (33 patients), physical (48 patients), role (56 patients) and social functioning (46 patients) were 50.9%, 70.1%, 54.6%, 45% and 57.8%, respectively. The estimated 12-month rates in terms of pain (46 patients), fatigue (63 patients) and nausea or vomiting (59 patients) were 54.2%, 39.7% and 41.3%, respectively.
The median treatment duration among all patients with brain metastases (263 patients) was 11.5 months, and 118 patients were still receiving Enhertu at the data cutoff.
“Estimated deterioration-free rates at 12-months were above 50% for cognitive, emotional, physical, and social functioning, [as well as] pain scores, regardless of the presence or absence of stable/active baseline brain metastases; further, the majority of patients had neurological stability at first score post baseline [86.6%], which was maintained throughout treatment in 55.1% of patients in the baseline brain metastases cohort and 72.9% of patients without baseline brain metastases,” Dr. Nadia Harbeck and coauthors wrote in a poster presentation of the data.
Harbeck is the director of the Breast Center, as well as the chair for Conservative Oncology and the head of the Oncological Therapy & Clinical Trials Unit in the Department of OB&GYN at LMU University Hospital in Munich, Germany.
In December 2019, the FDA granted accelerated approval to Enhertu for the treatment of patients with unresectable or metastatic HER2-positive breast cancer following 2 or more prior anti-HER2–based regimens in the metastatic setting. The approval was supported by findings from the phase 2 DESTINY-Breast01. The agent then received full approval in May 2022 for adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received an anti-HER2–based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within 6 months of therapy completion. That approval was based on findings from the phase 3 DESTINY-Breast03 trial.
DESTINY-Breast12 was a study that examined Enhertu in adult patients with HER2-positive metastatic breast cancer with or without baseline brain metastases.To be eligible, patients were allowed to receive up to two prior lines of therapy for metastatic brain cancer, excluding Tukysa (tucatinib). Other key inclusion criteria consisted of disease progression on prior HER2-directed regimens, an ECOG performance status of 1 or less, and no known or suspected leptomeningeal metastases.
Patients were divided into two cohorts: those with baseline brain metastases and those without (241 patients). Both cohorts received intravenous Enhertu at a dose of 5.4 milligram per kilogram every three weeks.
The primary end points were progression-free survival (PFS) in the brain metastases cohort and objective response rate (ORR). Secondary end points included central nervous system (CNS) PFS, time to progression, duration of response, overall survival, safety, HRQOL and neurological function.
Primary findings from DESTINY-Breast12 demonstrated that the 12-month PFS rates among all patients with brain metastases (263 patients), those with stable brain metastases (157 patients), and those with active brain metastases (106 patients), were 61.6%, 62.9% and 59.6%, respectively. The median PFS in the overall population was 17.3 months. The 12-month CNS PFS rates were 58.9%, 57.8% and 60.1%, for all patients with brain metastases, patients with stable brain metastases, and patients with active brain metastases, respectively. The respective confirmed ORRs were 51.7%, 49.7% and 54.7%.
Additional findings from the QOL analysis showed that the estimated 12-month deterioration-free rate in terms of GHS/QOL was 44.3% in evaluable patients without baseline brain metastases (128 patients).The estimated 12-month deterioration-free rates in terms of cognitive (112 patients), emotional (74 patients), physical (101 patients), role (128 patients) and social functioning (112 patients) were 54.9%, 69.1%, 61.3%, 45.3% and 51.1%, respectively. The estimated 12-month rates regarding pain (94 patients), fatigue (142 patients) and nausea/vomiting (143 patients) were 61.2%, 38.3% and 38.6%, respectively. The median treatment duration in the cohort of patients without brain metastases was 12 months.
Most patients without brain metastases (91.9%) had neuroglial stability at first score post baseline. Neuroglial stability was maintained throughout treatment in 72.9% of patients.
“Effects of trastuzumab deruxtecan (Enhertu ) on health-related quality of life (HRQOL) & neurological function in patients (pts) w/ HER2+ advanced/metastatic breast cancer (mBC) with or without brain metastases (BM): DESTINY-Breast12(DB-12) results” by Nadia Harbeck, et al. Presented at: San Antonio Breast Cancer Conference; December 10-13, 2024; San Antonio, TX. Abstract PS14-10.
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