The FDA has approved the use of fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of patients with unresectable or metastatic HER2-positive breast cancer who have previously received an anti-HER2 treatment in the metastatic, neoadjuvant, or adjuvant setting followed by disease recurrence during treatment or within 6 months of completing therapy, according to a press release from AstraZeneca.

The approval went through the FDA's Real-Time Oncology Review program, which converted the agent's accelerated approval to a standard approval. This indication now broadens the use of trastuzumab deruxtean plus a taxane therapy in HER2-positive metastatic breast cancer patients in the US.

The approval was based on findings from the phase 3 DESTINY-Breast03 trial (NCT03529110), which highlighted a reduction in risk of disease progression or death by 72% compared with trastuzumab emtansine (T-DM1; Kadcyla; HR, 0.28; 95% CI, 0.22-0.37; 

 <.0001). Findings from the trial were published in 

and indicated that the overall response rate was 79.7% (95% CI, 74.3%-84.4%) vs 34.2% (95% CI, 28.5%-40.3%) in both arms, respectively.

 Additionally, among those in the experimental cohort (n = 261), the 12-month progression-free survival rate was 75.8% (95% CI, 69.8%-80.7%) vs 34.1% (95% CI, 27.7%-40.5%) in the control group (n = 263).

The safety profile was consistent with previous findings, with no grade 4 or grade 5 treatment-related interstitial lung disease events being identified.

“This is an important day for the breast cancer community. With this approval, [trastuzumab] now provides a new treatment option for patients with HER2-positive metastatic breast cancer which can be used earlier in treatment to potentially delay progression of disease,” Catherine Ormerod, executive vice president of strategy and mission at Living Beyond Breast Cancer, said in the press release.

Enhertu approved in the US for patients with HER2-positive metastatic breast cancer treated with a prior anti-HER2-based regimen. News release. AstraZeneca. May 5, 2022. Accessed May 5, 2022. https://bit.ly/3OZHpSs

Cortés J, Kim SB, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. 

. 2022;386(12):1143-1154. doi:10.1056/NEJMoa2115022

Articles

Findings from the phase 3 DESTINY-Breast03 trial have led to the FDA approval of fam-trastuzumab deruxtecan-nxki for the treatment of patients with unresectable or metastatic HER2-positive breast cancer.

Trastuzumab Deruxtecan Receives FDA Approval for Metastatic HER2+ Breast Cancer

Trastuzumab Deruxtecan for HER2-positive Breast Cancer

In an interview with CancerNetwork® Sara Hurvitz, MD, associate professor at the David Geffen School of Medicine, medical director of the Johnson Comprehensive Cancer Center Clinical Research Unit, co-director of the Santa-Monica- University of California Los Angeles (UCLA) Outpatient Oncology Practices, and director of the Breast Cancer Clinical Trials Program at the University of California Los Angeles, spoke about additional clinical trials that are ongoing for the research of patients with or without brain metastases who have had previously treated metastatic HER2-positive breast cancer. Patients will be treated with fam-trastuzumab deruxtecan (T-DXd; Enhertu) with primary end points of objective response rate and progression-free survival.

The data relating to T-DXd for patients who have brain metastases are also exciting. We have a subgroup analysis from the Destiny-Breast03 trial that indicates about 60% of patients can have an intracranial objective response with T-DXd, which is higher than seen with T-DM1. These patients didn’t have progressive brain metastases or symptomatic brain metastases, but the data are nonetheless very intriguing from the [phase 2] TUXEDO-1 study (NCT04752059) which were presented as ESMO Breast further provides support that T-DXd may be active in progressive or untreated brain metastases. I’m really excited to see studies like [the phase 3] DESTINEY-Breast12 [trial; DESTINEY-Breast-12] provide further data in this area of unmet need for HER2-positive disease.

Videos

Sara Hurvitz, MD, spoke about ongoing clinical trials in which trastuzumab deruxtecan is being investigated with the use of brain metastases. 

Sara Hurvitz, MD, Spoke on Efficacy of T-DXd in HER2+ Breast Cancer With Brain Metastases

Sara Hurvitz, MD, associate professor at the David Geffen School of Medicine, medical director of the Johnson Comprehensive Cancer Center Clinical Research Unit, co-director of the Santa-Monica- University of California Los Angeles (UCLA) Outpatient Oncology Practices, and director of the Breast Cancer Clinical Trials Program at the University of California Los Angeles, spoke with CancerNetwork® about improvements in the treatment of HER2-positive breast cancer. She discussed the FDA approval of fam-trastuzumab deruxtecan (T-DXd; Enhertu) for patients with unresectable or metastatic HER2-positive breast cancer who have received prior anti-HER2-based treatments and its impact on the treatment paradigm.

The approval was based on the results of the phase 3 DESTINEY-Breast03 trial (NCT03529110), assessing the use of T-DXd vs ado-trastuzumab emtansine (T-DM1; Kadcyla).

The objective response rate was 79.7% (95% CI, 74.3%-84.4%) in the T-DXd arm vs 34.2% (95% CI, 28.5% vs 40.3%) in the T-DM1 arm.

Although HER2-positive breast cancer is now able to be treated with a number of HER2-targeted therapies, T-DXd is an agent that has demonstrated remarkable anti-tumor activity. HER2-positive breast cancer is a type of disease that is more aggressive biologically and [is] associated with worse outcomes including survival in the absence of HER2 targeted therapies. Although our HER2 targeted therapies are very important and have improved outcomes for patients, [those] diagnosed with metastatic disease that's HER2-positive still are not generally considered to be curable. T-DXd has achieved an impressive objective response, prolonged progression-free survival, and [yielded] a strong trend toward overall survival. All of these are improving outcomes for patients compared with the standard agents we have available for this disease.

Enhertu approved in the US for patients with HER2-positive metastatic breast cancer treated with a prior anti-HER2-based regimen. News release. AstraZeneca. May 5, 2022. Accessed May 20, 2022. https://bit.ly/3OZHpSs

Sara Hurvitz, MD, spoke to the difficulty of treating HER2-positive and advanced HER2-positive breast cancer and how the efficacy of novel agents such as fam-trastuzumab deruxtecan-nxki could make a difference in treating the disease.  



Sara Hurvitz, MD, Speaks to Improvements in Treatment for HER2+ Breast Cancer

During an interview with CancerNetwork®, Sara Hurvitz, MD, associate professor at the David Geffen School of Medicine, medical director at the Johnson Comprehensive Cancer Center Clinical Research Unit, co-director of the Santa Monica University of California Los Angeles (UCLA) Outpatient Oncology Practices, and director of the Breast Cancer Clinical Trials Program at the UCLA, discussed the approval of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for patients with unresectable or metastatic HER2-positive breast cancer who have received prior anti-HER2-based treatments.

The approval was based on the results of the phase 3 DESTINY-Breast03 trial (NCT03529110) which assessed the use of T-DXd vs ado-trastuzumab emtansine (T-DM1; Kadcyla).

 A 72% reduction in the risk of disease progression or death was observed in the T-DXd arm compared with the T-DM1 arm (HR, 0.28; 95% CI, 0.22-0.37; 

T-DXd has been approved now for a couple of years based on an accelerated approval, so patients have already had access to T-DXd. [However], the full approval for patients in the second-line setting and beyond is a great news for patients. We saw data from the DESTINY-Breast03 clinical trial that indicates T-DXd is better in terms of progression-free survival [PFS] and overall survival [OS] than T-DM1 in patients previously treated with at least 1 prior line of therapy. This now makes this drug technically available to our patients in the second-line setting and later, and the responses that we’re seeing with PFS, which was statistically significantly improved with T-DXd, are quite impressive. There’s a strong trend toward an improvement in OS that hasn’t yet met statistical significance but is very exciting and very encouraging. For patients diagnosed with HER2-positive breast cancer, this is big news.

Sara Hurvitz, MD, spoke about to recent approval of fam-trastuzumab deruxtecan-nxki in the second-line setting for patients with HER2-positive breast cancer. 