New Study Shows Effectiveness of HER2 Immunoconjugates in Metastatic Breast Cancer with Ultra-Low Protein Levels

Compilation
Results Destiny-06 Phase 3 Clinical Study demonstrate that the conjugated antibody Trastuzumab deruxtecan (T-DXd) provides better results than traditional chemotherapy in patients with hormone receptor positive (RH+) metastatic breast cancer. low or ultra-low levels of HER2 proteinwho have previously received one or more lines of endocrine therapy, but not chemotherapy for metastatic disease.

In Spain, about 70% of breast tumors are RH+ HER2- type. But the researchers found that among those considered HER2-, there is a spectrum of expression of this protein that is considered low (short) or ultra low(ultra-low). “These tumors can be helped by already approved drugs that have good results in HER2+ tumors.”points to Dr. Cristina SauraHead of the Breast Cancer Unit at the Val d’Hebron University Hospital, Head of the Breast Cancer Group at the Val d’Hebron Institute of Oncology (VHIO) and co-author of the essay published in the journal. New England Journal of Medicine (NEJM).

Median progression-free survival for patients with low and ultra-low HER2 levels who received the immunoconjugate was 13.2 months, compared with 8.1 months for those who received chemotherapy.

There was already a previous study called Destiny-04, also published in 2022 in the journal NEMJ, the results of which led to the approval of the T-DXd immunoconjugate in patients with HR+ metastatic breast cancer and low HER2 expression. Funding for this indication was recently approved in Spain.

“Following these results, we think that more patients considered HER2-negative may benefit from anti-HER2 treatments earlier in their disease treatment.”Saura explains. And then the Destiny-06 study arose to determine whether the immunoconjugate was effective and safe in patients with this type of metastatic breast cancer with low or ultra-low HER2 expression. The study included 866 patients meeting these criteria..

Dr. Saura: “Treatment with T-DXd, which targets the HER2 protein, even at ultra-low levels, may provide a therapeutic advantage over traditional chemotherapy.”

In patients with low HER2 levels treated with T-DXd, Reduced risk of disease progression by 38% compared with those treated with chemotherapy. The median progression-free survival, that is, the time from the start of treatment to tumor regrowth, was 13.2 months in patients treated with conjugated antibody versus 8.1 months in patients receiving chemotherapy. These results were also consistent in the subgroup of patients with ultra-low HER2 levels (153).

“These results are especially relevant because suggest that T-DXd treatment targets the HER2 protein, even at very low levels.may provide a therapeutic advantage over traditional chemotherapy for these patients, expanding the number of people who can benefit from anti-HER2 therapies earlier in the treatment of metastatic breast cancer.” says Dr. Cristina Saura.

The researcher comes to the conclusion that “Although this new treatment indication has not yet received regulatory approval or funding in Spain, the results This study opens the door to new treatment options in the future for patients with metastatic breast cancer with low or ultra-low expression of HER2″.