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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