Dato-DXd May Be Better Tolerated Than Chemo in HR+/HER2– Breast Cancer

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Safety data further support datopotamab deruxtecan as a new treatment option in metastatic hormone receptor–positive, HER2-negative breast cancer.

Patients with previously treated, inoperable or metastatic, hormone receptor (HR)–positive, HER2-negative breast cancer experienced fewer side effects when treated with datopotamab deruxtecan (dato-DXd)versus those treated with chemotherapy, according to recent findings.

Safety analysis from the phase 3 TROPION-Breast01 trial was presented at the 2024 European Society for Medical Oncology (ESMO) Breast Cancer Annual Congress.

Study Highlights:

  • Dato-DXd is an antibody-drug conjugate, a type of treatment designed to deliver a payload of cancer-killing drugs directly to tumor cells, thereby intended to spare healthy cells.
  • Dato-DXd is being studied as a treatment for patients with previously treated, inoperable or metastatic, hormone receptor-positive, HER2-negative breast cancer. In a recent study, patients with this type of breast cancer who received Dato-DXd experienced fewer side effects than those treated with chemotherapy.
  • The study found that the rates of grade 3 or higher (severe or worse) treatment-related side effects was 20.8% in the Dato-DXd group, versus 44.7% in the chemotherapy group.
  • Dato-DXd is still being studied and is not currently a standard treatment for breast cancer.

With a median treatment duration of 6.7 months and 4.1 months with dato-DXd and investigator’s choice of chemotherapy, respectively, the rates of grade 3 or higher (severe or worse) treatment-related side effects was 20.8% in the dato-DXd group versus 44.7% in the chemotherapy group. Additionally, 20.8% and 30.2% of patients from each respective arm had a dose reduction following side effects, and toxicity leading to dose interruptions occurred in 11.9% and 24.5%.

“These data further support dato-DXd as a potential new therapeutic option for patients with previously treated, inoperable or metastatic HR–positive, HER2-negative breast cancer,” Dr. Komal Jhaveri, section head of the Endocrine Therapy Research Program, clinical director of Early Drug Development Service, and the Patricia and James Cayne Chair for Junior Faculty at Memorial Sloan Kettering Cancer Center in New York, said in a presentation of these data.

Dato-DXd is an antibody-drug conjugate, a type of treatment designed to deliver cancer-killing drugs directly to tumor cells, thereby intended to spare healthy cells. Research presented in December 2023 showed that the drug may improve outcomes in HR-positive, HER2-negative inoperable or metastatic breast cancer.

About TROPION-Breast01

In the phase 3 TROPION-Breast01 trial, 365 patients were randomly assigned to receive dato-DXd while 367 were assigned to receive investigator’s choice of chemotherapy. Treatment choices in the chemotherapy arm included eribulin mesylate, vinorelbine, gemcitabine or capecitabine.

The trial’s dual primary end points were progression-free survival (the time patients live without their disease spreading or worsening) and overall survival (the time patients live, regardless of disease status). Secondary end points included objective response rate (the percentage of patients who responded partially or completely to treatment) and safety.

Patients with HR-positive, HER2-negative breast cancer who received one or two prior lines of chemotherapy in the inoperable or metastatic setting were eligible for enrollment on the trial. Other eligibility criteria included having disease progression on endocrine therapy and an ECOG performance status of 0 or 1 (meaning patients could perform daily tasks but may be restricted in strenuous physical activity).

Dato-DXd Side Effects

Additional analysis showed that side effects of special interest — including oral mucositis or stomatitis (inflammation or sores in the mouth), damage to the eye’s surface and adjudicated drug-related interstitial lung disease (ILD; inflammation and scarring of the lung) — were found to be low grade and manageable in the dato-DXd arm.

Oral mucositis and stomatitis, according to the American Cancer Society, refer to mouth sores that result from damage caused by cancer treatment to the cells that line the mouth, throat and gastrointestinal tract.

Any-grade treatment-related mucositis or stomatitis affected 55.6% of patients in the dato-DXd arm, with grade 3 (severe) events reported in 6.9%; the median time to onset was 22 days, and the median time to resolution was 36.5 days. Additionally, 13.3%, 1.4%, and 0.3% of patients had dose reductions, interruptions and discontinuations following these toxicities, respectively. Investigators managed these toxicities by using a steroid-containing mouthwash as well as preventative cryotherapy — which, according to the American Cancer Society, involves the paient sucking on ice chips before, during and after infusions of chemotherapy treatments.

Any-grade and grade 3 ocular surface events (damage to the surface of the eye), respectively, occurred in 40% and 0.8% of patients who received dato-DXd. The median time to onset was 65 days, and the median time to resolution was 67 days. Rates of dose reduction and/or interruption and dose discontinuation due to this toxicity were 3.3% and 0.3%, respectively. Based on toxicity management guidelines, investigators mitigated these ocular surface events by using artificial tears daily and recommending that patients avoid contact lenses.

Regarding adjudicated drug-related ILD, any-grade and grade 3 or higher events were reported in 3.3% and 0.8% of patients, respectively, in the dato-DXd arm. The median time to onset was 84.5 days, and these events resolved at a median of 28 days. Events leading to dose reductions, interruptions and discontinuation, respectively, occurred in 0.3%, 0.8%, and 1.4% of patients.

Any-grade hematological (blood-related) toxicities of interest in the dato-DXd arm and chemotherapy arms, respectively, included neutropenia (low count of neutrophils, a type of white blood cell; 10.8% versus 42.5%), anemia (low red blood cells; 11.1% versus 19.7%) and leukopenia (low white blood cell count; 7.2% versus 17.1%). Of note, grade 3 or higher neutropenia occurred in 30.8% of those in the chemotherapy arm. Investigators administered granulocyte colony stimulating factor (G-CSF) to 2.7% of patients in the dato-DXd arm compared with 22.1% of those who received chemotherapy. G-CSF is a protein that stimulates white blood cell growth in the bone marrow.

Other any-grade treatment-related side effects of interest in patients who received dato-DXd and chemotherapy, respectively, were nausea (51.1% versus 23.6%), diarrhea (7.5% versus 12.3%), alopecia (hair loss; 36.4% vs 20.5%) and peripheral neuropathy (pain, numbness or tingling in the hands and feet, 3.6% versus 13.7%). These toxicities were mitigated with anti-emetic agents (medications used to manage nausea and vomiting) given before dato-DXd infusion and on subsequent days whenever necessary.

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