Trastuzumab Deruxtecan vs. Herceptin: How Do These Breast Cancer Drugs Compare?

The Food and Drug Administration has granted priority review for trastuzumab deruxtecan for the treatment of human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer. If approved, the experimental drug, a joint effort from AstraZeneca and Daiichi Sankyo, would compete with longstanding HER2+ drug trastuzumab, marketed as Herceptin and manufactured by Roche.

Study Outcomes: Trastuzumab Deruxtecan

Two reports published this year detailed outcomes associated with trastuzumab deruxtecan; both appeared in The Lancet Oncology, and one reported phase 1 trial results in HER2+ advanced-stage breast cancer patients previously treated with trastuzumab emtansine who received trastuzumab deruxtecan. Patients received the recommended doses for expansion of 5.4 mg/kg or 6.4 mg/kg trastuzumab deruxtecan intravenously once every three weeks. Patients were treated until study withdrawal, unacceptable toxicity, or progressive disease. The main outcome measures were safety and preliminary activity. Over about a three-year period, 115 of 118 HER2+ breast cancer patients received at least one dose of trastuzumab deruxtecan at the recommended doses for expansion. At least one treatment-related adverse event (AE) occurred in all patients. The most common grade 3 or worse AEs were anemia (17%) and decreased neutrophil (14%), white blood cell (9%), and platelet (8%) counts; 19% of patients had at least serious treated-related AE. Twenty cases of interstitial lung disease, pneumonitis, or organizing pneumonia were reported; this included one grade 3 event and two treatment-related deaths as a result of pneumonitis. One death occurred that was not related to the study. An objective response was confirmed in 59.5% of patients.

The DESTINY-Breast01 trial is a phase 2 study that, according to a press release, achieved similar outcomes to those seen in the phase 1 trial data. Results from this study will be presented in December at the San Antonio Breast Cancer Symposium.

Study Outcomes: Trastuzumab

A 2017 study published in The Lancet reported 11-year outcomes for women with HER2+ early breast cancer taking trastuzumab. The trial included 5,102 women from hospitals spanning 39 countries. Women were randomized 1:1:1, after completing primary therapy (surgery, chemotherapy, and/or surgery), either to receive trastuzumab for one year (once at 8 mg/kg of bodyweight intravenously, then 6 mg/kg once every three weeks) or for two years (with the same dose schedule), or to the observation group. The main outcome measure was disease-free survival. The final analysis included 5,099 patients randomized to the observation (n = 1,697), one-year trastuzumab (n = 1,702), and two-year trastuzumab (n = 1,700) groups. Median follow-up time was 11 years. Patients assigned to the one-year trastuzumab group, compared to the observation group, had a significantly lower risk of a disease-free survival event (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.68–0.86) and death (HR 0.74, 95% CI 0.64–0.86). compared to the one-year group, two years of add-on trastuzumab was not associated with improved disease-free survival (HR 1.02, 95% CI 0.89–1.17). Ten-year disease-free survival rates were 63% in the observation group and 69% in both trastuzumab groups. More than half (52%) of the observation group switched to a treatment group. Cardiac toxicity was most frequent during the treatment phase but low in all three groups; secondary cardiac endpoint incidence rates were 7.3% in the two-year trastuzumab group, 4.4% in the one-year trastuzumab group, and 0.9% in the observation group.

According to the Herceptin website, the treatment is indicated for use in HER2+ metastatic breast cancer patients in conjunction with another therapy, or alone after other therapies have been attempted.

According to drugs.com, 150 mg Herceptin intravenous powder for injection costs about $1,636.49.

Kaitlyn D’Onofrio is a digital medical writer. She is interested in musculoskeletal health, the effect of exercise on health, and mental health awareness. When she’s not writing for DocWire, Kaitlyn is teaching yoga classes in her community, promoting wellness to her students.