HER3-Directed Therapy Was Effective and Safe in Breast Cancer Subtype

Patritumab deruxtecan, a HER3-directed antibody drug conjugate, was safe and effective in the treatment of patients with heavily pretreated estrogen receptor (ER)-positive and triple-negative metastatic breast cancers, according to results from a recent study.

Findings from this phase 2 study were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

The overall response rate (the percentage of patients with a partial or complete response to treatment) was 35% and the clinical benefit rate (percentage of patients with a complete response, partial response or stable disease for at least six months) was 43.3%. In heavily pretreated patients, the overall response rate was 35%, the overall clinical benefit rate was 43%, and the duration of response (the time from a therapeutic response to disease progression or all-cause death) was at least six months in about half of those who responded.

“Clinical activity of patritumab deruxtecan was observed across a broad range of HER3 membrane expression levels in patients with heavily pretreated ER-positive and triple-negative breast cancer. This is consistent with emerging data,” Dr. Erika P. Hamilton, director of breast cancer and gynecologic cancer research at Sarah Cannon Research Institute in Nashville, Tennessee, said during the presentation.

Of the patients enrolled, 71.7% were between the ages of 18 and 65 and 98.3% were women. The median lines of prior therapy were three in the metastatic setting. In 21.7% of patients, stage 4 disease was present at diagnosis. It was noted that 3.3% of patients had a BRCA1 mutation and 1.7% had a BRCA2 mutation.

When disease type was investigated, 32% had triple-negative breast cancer and 48% had hormone receptor-positive breast cancer. Additionally, 48% of patients had liver metastases and 32% had lung metastases.

Researchers focused on several outcomes including overall response rate, six-month progression-free survival, safety and tolerability, duration of response and the clinical benefit rate.

Patients must be 18 years or older with an ECOG performance score of 0 (considered fully active with no performance restrictions) or 1 (able to carry out light work but restricted on strenuous physical activity); have locally advanced or metastatic breast cancer with one or more measurable lesions; HER2-negative; or hormone receptor-positive-or-negative.

As of the data cutoff, 35% of patients remained on study treatment and 65% had discontinued. The primary reasons for discontinuation were side effects (13.1%), progressive disease (41.7%), death (3.3%) and physician or patient decision (6.7%). The duration of treatment while on the study was 5.9 months.

The median treatment duration was 5.2 months, and 21 patients continued with treatment at the data cutoff. In total, 43.3% of patients continued receiving patritumab deruxtecan for six months or more. In the overall population, the best overall response was a partial response in 35% of patients, stable disease in 43.3% and progressive disease in 11.7%.

In patients who had HER3 expression of 75% or more and either ER-positive (16 patients) or triple-negative (11 patients) disease, the overall response rate was 37.5% vs 18.2%, the clinical benefit rate was 50% vs 18.2%, and the proportion achieving a duration of response of 6 months or more was 50% vs 50%, respectively.

In patients who had HER3 expression of 25% to 74% and either ER-positive (5 patients) or triple-negative (5 patients) disease, the overall response rate was 60% vs 20%, the clinical benefit rate was 60% vs 40%, and the proportion achieving a duration of response of six months or more was 33.3% vs 0%, respectively.

In patients who had hormone-positive disease (29 patients) and triple-negative breast cancer, the overall response rate was 41.4% vs 21.1%.

Treatment-related side effects were observed in 93% of patients, and 31.7% experienced treatment-related side effects considered severe or worse. The most common severe or worse treatment-related side effects included fatigue (6.7%), diarrhea (5%), neutrophil count decrease (5%) and nausea (3.3%).

Treatment-emergent serious side effects occurred at various rates, with the most common being interstitial lung disease (causes scarring of the lungs), nausea/vomiting, lung inflammation and thrombocytopenia (lower than normal number of platelets in blood). Unrelated serious side effects included shortness of breath, pneumocystis jirovecii pneumonia (a fungal lung infection) and pneumothorax (air outside the lung but within the pleural cavity).

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