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Data from the phase 3 DESTINY-Breast06 trial were presented during the 2024 San Antonio Breast Cancer Symposium.
Patients with hormone receptor (HR)-positive, HER2-low/-ultralow metastatic breast cancer experienced improvements to progression-free survival (PFS) from treatment with Enhertu (fam-trastuzumab deruxtecan-nxki) when compared with treatment of physician’s choice (TPC), no matter the time to progression (TTP) on frontline endocrine therapy with CDK4/6 inhibition and the type of endocrine resistance, study results have shown.
Data from the phase 3 DESTINY-Breast06 trial were presented during the 2024 San Antonio Breast Cancer Symposium.
In the population of patients who had a TTP of less than six months, the median PFS was 14 months with Enhertu versus 6.5 months with TPC. Patients with a TTP between 6 and 12 months had a median PFS of 13.2 months with Enhertu versus 6.9 months with TPC. Patients who went more than 12 months before progressing on frontline therapy experienced a median PFS of 12.9 months with Enhertu versus 8.2 months with TPC.
Progression-free survival (PFS): the time a patient lives without their disease spreading or worsening.
Objective response rate (ORR): patients who responded partially or completely to treatment.
Duration of response (DOR): how long a patient responds to treatment.
Time to second progression: the time until a second disease progression.
Moreover, the median PFS was 12.4 months with Enhertu versus 6.6 months with TPC in patients with primary endocrine resistance. Patients with secondary endocrine resistance achieved a median PFS of 13.2 months with Enhertu versus 9.5 months with TPC.
“[Enhertu] demonstrated a clinically meaningful efficacy benefit versus TPC regardless of time to progression on frontline endocrine therapy plus CDK4/6 inhibition, as well as efficacy regardless of disease burden,” Dr. Aditya Bardia, lead study author and professor in the Department of Medicine, Division of Hematology/Oncology at UCLA Health’s Jonsson Comprehensive Cancer Center in Los Angeles, California, said in a presentation of the data.
The multi-center, open-label DESTINY-Breast06 trial enrolled patients with hormone receptor-positive metastatic breast cancer with HER2-low or HER2-ultralow expression. Patients could not have received prior chemotherapy and must have had at least two prior lines of endocrine therapy with or without targeted therapy for metastatic disease or received one line of therapy for metastatic disease and developed progression within six months of starting frontline endocrine therapy with a CDK4/6 inhibitor or developed recurrence within 24 months of starting adjuvant endocrine therapy.
Patients were randomly assigned evenly to 5.4 milligrams per kilogram (mg/kg) of Enhertu every 3 weeks (436 patients) or TPC (430 patients), which consisted of Xeloda (capecitabine; 59.8%), Abraxane (nab-paclitaxel; 24.4%) or paclitaxel (15.8%).
The study had previously met its primary end point, demonstrating an improvement in PFS in the HER2-low population. A key secondary end point of PFS in the HER2-low/-ultralow population was also met.
“The objectives of this analysis were to investigate the benefit of Enhertu in patients with different responses to endocrine therapy, assess the efficacy of subsequent therapies post progression on Enhertu/TPC and understand the benefit of Enhertu in patients with varying disease burdens,” Bardia said.
Investigators also found that Enhertu improved the objective response rate (ORR) and duration of response (DOR) versus TPC across all TTP subgroups and in patients with primary and secondary endocrine resistance. The confirmed ORRs with Enhertu and TPC, respectively, were 67.7% and 25.4% in patients with a TTP of less than six months; 60% and 28.8% in patients with a TTP between six and 12 months; and 59.5% and 33.1% in patients with a TTP greater than 12 months.
The confirmed ORRs were 57.8% and 25.7% with Enhertu and TPC, respectively, in patients with primary endocrine resistance; and 57.1% and 34.0%, respectively, in those with secondary endocrine resistance.
The median DOR with Enhertu and TPC, respectively, in patients with a TTP of less than six months, between six and 12 months, and greater than 12 months were as follows: 11.1 months versus 7.3 months; 13.7 months versus 11.5 months and 15.7 months versus 11.1 months. The median DOR was 11.1 months with Enhertu versus 7.3 months with TPC in patients with primary endocrine resistance and 15.4 months versus 10.1 months in those with secondary endocrine resistance.
Time to second progression (PFS2), which served as a secondary end point of the trial, was also presented in the intention-to-treat population (866 patients). Findings showed that the median PFS2 was 20.3 months with Enhertu versus 14.7 months with TPC. Bardia stated that PFS2 was clinically meaningful in favor of Enhertu across all TTP subgroups. Patients with a TTP of less than six months had a median PFS2 of 18.9 months with Enhertu versus 15.2 months with TPC. Patients with a TTP between six and 12 months had a median PFS2 of 17.1 months with Enhertu versus 13.7 months with TPC. Patients with a TTP greater than 12 months had a median PFS2 of 20 months with Enhertu versus 14.3 months with TPC.
“PFS benefit with [Enhertu] was [also] observed regardless of disease burden, with notable efficacy in patients with lower disease burden,” Bardia said. In patients with less than three local or metastatic sites at baseline the median PFS was 15.3 months with Enhertu versus 8.4 months with TPC. Among patients with at least three local or metastatic sites at baseline the median PFS was 11.4 months with Enhertu versus 7.2 months with TPC.
Enhertu also improved PFS versus TPC in patients with and without liver metastases, a baseline tumor size greater and lower than the median and those with and without visceral disease.
With respect to safety, Bardia explained that the safety profiles for Enhertu and TPC in the TTP and disease burden subgroups were consistent with the overall population.
Reference
“Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) by pace of disease progression on prior endocrine-based therapy: additional analysis from DESTINY-Breast06” by Dr. Aditya Bardia et al., presented at: San Antonio Breast Cancer Conference; December 10-13, 2024; San Antonio, Texas.
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