Patient-Reported Outcomes Support Use of Trastuzumab Deruxtecan in HR+/HER2-Negative Breast Cancer

Naoto T. Ueno, MD, PhD, FACP

Fam-trastuzumab deruxtecan-nxki (Enhertu) preserved quality of life vs physicians choice of treatment in patients with advanced, hormone receptor (HR)–positive/HER2-low metastatic breast cancer, according to patient-reported outcome (PRO) data from the DESTINY-Breast04 (NCT03734029) trial.¹

In findings presented at the 2022 ESMO Congress, investigators found that the antibody-drug conjugate delayed deterioration of global health status in this cohort. Furthermore, trastuzumab deruxtecan also maintained global health status and quality of life for HR-positive throughout the treatment period.

“This PRO data gives more of a confidence to physicians, as patient-reported outcomes are always important,” said lead author Naoto T. Ueno, MD, PhD. “In the DESTINY-Breast04 trial, the treatment was able to have similar outcomes in both the high and low-HER2 populations.”

In an interview with OncLive^®, Ueno, a faculty member in the Department of Breast Medical Oncology, Division of Cancer Medicine, at the University of Texas MD Anderson Cancer Center, discusses how the patient-reported outcomes from the DESTINY-Breast04 trial will impact future research in patients with HER2-low breast cancer.

OncLive^®: Can you give us some background on the pivotal DESTINY-Breast04 trial?

Ueno: The DESTINY-Breast04 trial targets HER2-low metastatic breast cancer with 1 or more prior lines of chemotherapy. Moreover, HER2-low is defined as immunohistochemical staining 1+ or 2+ with a FISH being negative.

This is a phase 3 study comparing trastuzumab deruxtecan vs physician choices of treatment. The outcomes were discussed at the 2022 ASCO Annual meeting by Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center. These data proved that there is a significant improvement of progression-free survival [PFS; with trastuzumab deruxtecan], which is the primary end point of the trial. Moreover, the secondary end point of overall survival was proven to be statistically significant.

This study had an additional evaluation of economic impact, as well as a patient-reported outcome quality of life assessment. This was part of a planned analysis that if the efficacy was significant, researchers would study the HR-positive quality of life assessment.

What was unique about these patients?

The important part to understand is that in this landscape, 70% of patients were exposed to CDK4/6 inhibitors. This is a first line treatment for the HR-positive, HER2-negative metastatic breast cancer.

What methods did you use to evaluate quality of life?

To study the quality of life, researchers used 3 different validated surveys or questionnaires. The questionnaire had cancer specific, breast cancer specific, or general questions. These questionnaires were tested at the baseline, through the entire treatment, and even after the treatment.

What did you find?

We have shown that the global health status, which is part of the questionnaire, is well maintained throughout the course of treatment trastuzumab deruxtecan. Treatments lasted up to 27 cycles, and yet there was no deterioration. A similar result was noted with the treatment of physicians choice therapy, proving that general quality of life is well maintained.

Investigators also examined detailed symptoms such as fatigue, nausea, and pain. When looking at those data, the fatigue was well [controlled]. Pain was significantly improved by treatment [with] trastuzumab deruxtecan compared with treatment with physician’s choice therapy. The nausea was one of the issues [in the experimental arm], as nausea is known to be more prominent with trastuzumab deruxtecan compared to regular chemotherapy.

It was noticed in cycle 2 and in cycle 5 that there was a deterioration of the patient-reported outcomes. However, this was quickly corrected, and it was reduced over the course of the trial. There was no accumulated effect, and it was stable over the course of the entire treatment.

Were there any surprises to note in these findings?

There were no surprises. However, it was impressive in terms of the overall quality of life improvement, including overall functionality and symptoms. Most of the hazard ratios were ranging from 0.4 to 0.72. The only thing that was on the opposite side was the nausea.

Other than the nausea, everything improved. That’s quite impressive considering that this is a metastatic breast cancer treatment.

What did your findings mean for this patient population?

We know the efficacy of this treatment, as that’s already well known, and we know the adverse effects. The point is that from the, finding the balance between the efficacy and safety, it proves that patient have a reasonable and good quality of life by receiving this treatment. Additionally, it does prolong the deterioration from reaching a deterioration condition due to the disease progression, so it was quite impressive.

What do these results add to what is already known about trastuzumab deruxtecan in this setting?

This PRO data gives more of a confidence to physicians, as patient-reported outcomes are always important. In the DESTINY-Breast04 trial, the treatment was able to have similar outcomes in both the high and low-HER2 populations.

In terms of efficacy and toxicity, even with the best efficacy, this doesn’t mean the patient appreciates the treatment, due to the toxicity. However, with a full confidence in the metastatic breast cancer setting, this treatment is really impacting the quality of life, which is a good thing for the patients.

What would you like your colleagues to know about this research?

The main takeaway message revolves around a few things. First, the quality of life will be maintained [with trastuzumab deruxtecan]. However, the nausea is something that researchers must pay attention to. Overall, in early course of the treatment, the nausea is prominent than in the regular chemotherapy.

Most of us know how to manage the nausea, but this data does suggest that we must be very aggressive about managing nausea, because nausea could contribute to a very poor quality of life. Symptomatically, the focus should be more nausea than anything else.

Reference

1. Ueno NT, Jacot W, Yamashita T, et al. Patient-reported outcomes (PROs) from DESTINY-Breast04, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2-low metastatic breast cancer (MBC). Ann Oncol. 2022;33(suppl 7):S88-S121. doi: 10.1016/annonc/annonc1040