Sarah Donahue Highlights Destiny-Breast04 Trial Takeaways for Patients With HR+, HER2-Low Metastatic Breast Cancer


Sarah Donahue, MPH, NP, AOCNP, explains the trial design of the pivotal DESTINY-Breast04 trial and discusses how the promising performance of trastuzumab deruxtecan might impact patients with unresectable or metastatic HER2-low breast cancer.

For this episode of The VitalsOncology Nursing News® met with Sarah Donahue, MPH, NP, AOCNP, a nurse practitioner at the University of California San Francisco Health, to discuss findings from the findings of DESTINY-Breast04 trial (NCT03734029).

DESTINY-Breast04, a phase 3, open-label pivotal trial, randomly assigned patients with unresectable or metastatic HER2-low breast cancer to receive the fam-trastuzumab deruxtecan-nxki (Enhertu) at 5.4 mg/kg every 3 weeks (n = 373) or physician’s choice chemotherapy at locally approved dosing (n = 184). All enrolled patients had already received at last 1 prior line of therapy in the metastatic setting.1,2

The primary end point was progression-free survival (PFS) in patients with hormone receptor–positive breast cancer. The median PFS in the primary end point population was 10.1 months (95% CI, 9.5-11.5) with the antibody-drug conjugate vs 5.4 months (95% CI, 4.4-7.1) with standard of care (HR, 0.51; 95% CI, 0.40-0.64; P < .0001). The median overall survival was 23.9 months (95% CI, 20.8-24.8) vs 17.5 months (95% CI, 15.2-22.4), respectively (HR, 0.64; 95% CI, 0.48-0.86; P = .003).1,2

These findings, according to Donahue, will result in the addition of another therapy that patients with unresectable or metastatic HER2-low breast cancer can benefit greatly from.

“One significant part [of] this trial is that included such a large population of patients,” Donahue says. “It really captured most patients with metastatic breast cancer—[there were] patients with liver metastases, lung metastases, and brain metastases that were stable. It really covered a very large representative group of patients.”

Further, Donahue adds, “The data that were presented at the [2022 ASCO Annual Meeting] showed that the patients that received the trials trastuzumab deruxtecan had a much [improved] PFS compared with those patients that were on the physician’s choice of chemotherapy. [Investigators] found that they could increase the median PFS from 5 months to about 10 months, so they could double it,” Donahue explains. “It was similar with the patients with hormone [receptor]–positive diseases, as with the entire population. It did not matter what the hormone receptor status was for these patients, [they all] received that benefit.”

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  1. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): results of DESTINY-Breast04, a randomized, phase 3 study. J Clin Oncol. 2022;40(suppl 17):LBA3. doi:10.1200/JCO.2022.40.17_suppl.LBA3
  2. Modi S, Jacot W, Yamashita T, et al; DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690

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