Enhertu May Further Improve Survival Versus Xeloda Regimens in HER2-Positive Breast Cancer

Patients with advanced HER2-positive unresectable and/or metastatic breast cancer who were previously treated had a 34% reduction in death a 13-month average increase in survival when treated with Enhertu (fam-trastuzumab-deruxtecan-nxki) versus a Xeloda (capecitabine)-based regimen, according to recent trial results.

Results from the phase 3 DESTINY-Breast02 trial were presented at the 2022 San Antonio Breast Cancer Symposium.

In an interview with CURE®, study author Dr. Ian Krop, a chief clinical research officer at the Yale Cancer Center in New Haven, Connecticut, discussed how Enhertu targetsHER2-positive breast cancer and the important role the study has played in confirming the efficacy of Enhertu for patients with this subset of breast cancer.

How Enhertu Targets Cancer Cells

Krop explained that Enhertu is an antibody-drug conjugate, which is “a drug that is built on an antibody, which is a synthetic protein that’s very specific for one thing. We make these antibodies against something on the surface of a cancer cell.”

He added that in this case, the antibody is made against HER2, a protein that is on HER2 positive breast cancer. “If you inject (Enhertu) into the blood of a patient, the antibody is going to go through the bloodstream, find all the HER2 on the cancer cells, stick to it, and not touch anything else,” Krop said.

Krop added that the antibody is linked to a potent chemotherapy drug before the injection, which aids in its selective treatment approach.

“(It’s) like a guided-missile approach,” he said. “The advantage here is by delivering the chemo right to the cancer cell, you’re able to cut down some of the side effects of the chemotherapy because the chemo is going right to the cancer cell and hopefully not hurting normal tissue.”

Comparing Enhertu With Xeloda

In the trial, 608 patients with metastatic breast cancer who had previously received two lines of treatment with Kadcyla (trastuzumab emtansine) received Enhertu alone or a combination of Xeloda with either Herceptin (trastuzumab) or Tykerb (lapatinib). In particular, 406 patients received Enhertu whereas 202 patients received a Xeloda combination.

During the presentation, Krop said that the median progression-free survival (median time the patient lives with the cancer without the disease worsening) was 17.8 months for patients with Enhertu compared with 6.9 months for patients treated with the Xeloda combination, demonstrating a 64% reduction in the risk for disease progression or death.

Findings from the trial also demonstrated that after two years, 42% of patients who received Enhertu did not have more advanced disease compared to 13.9% of patients who received the Xeloda combination.

After one year, 89.4% of patients in the Enhertu group were alive compared with 74.7% of patients in the Xeloda group. Patients in the Enhertu arm survived a median 39 months and while patients in the Xeloda arm survived a median 26.5 months. Krop explained that there was a 34% reduction in the risk of death with Enhertu compared to the Xeloda combination.

Looking to the Future

Krop said that while this was a confirmatory study that does not currently change standard of care, the results leave him optimistic for the future of targeted therapy for breast cancer.

“From a big-picture standpoint, for patients with HER2-positive breast cancer, these data just confirm that there’s a number of very effective drugs available for them, and that really hasn’t changed with the results of this trial,” Krop said.

He noted that Enhertu was also recently approved for patients in the newly designated subtype of HER2-low breast cancer. Approvals like those highlight the importance of patients speaking with their providers about their cancer subtype.

“It’s important for patients to understand what their tumor looks like, is it HER2-positive, which is about 15% to 20% of breast cancers, or is it HER2-low which is actually more like 60% of breast cancers,” Krop explained. “(Enhertu) works in both, but exactly when you use it differs between those two groups.”

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