While treatment with trastuzumab is the standard of care for HER2-positive locally advanced or metastatic breast cancer and gastric cancer, data on long-term use of the biologic are lacking, and cardiac risk related to trastuzumab has posed concerns.
While treatment with trastuzumab is the standard of care for HER2-positive locally advanced or metastatic breast cancer and gastric cancer, data on long-term use of the biologic are lacking, and cardiac risk related to trastuzumab has posed concerns. In a new study in BMC Cancer, researchers reported findings from the Rollover Protocol Study that collected safety data on long-term trastuzumab therapy (5 or more years in patients with HER2-positive breast cancer and 3 or more years in patients with gastric cancer).
In total, 19 patients with breast cancer and 6 patients with gastric cancer who had stable disease received long-term trastuzumab therapy during the study. The patients previously treated with trastuzumab continued to receive the drug at a loading dose of 4 mg/kg followed by weekly 2-mg/kg maintenance doses beginning 3 weeks after the loading dose. Therapy continued until progression, lack of treatment benefit, toxicity, patient decision, or patient death.
All patients discontinued treatment by the study’s end, due to adverse events (AEs), insufficient response, a switch to commercially available trastuzumab or subcutaneous trastuzumab outside the study context, patient decision, investigator decision, or sponsor request. The median duration of treatment in the breast cancer group was 8 years and 7 months (range, 5 years and 4 months to 13 years and 11 months). In the gastric cancer group, the median duration of treatment was 5 years and 2 months (range, 3 years and 4 months to 7 years and 4 months).
While the risk of cardiac AEs is a concern with trastuzumab treatment, in the 20 patients who had left ventricular ejection fraction (LVEF) measurements available, the cardiac status of these patients remained stable over time; no marked changes in LVEF were observed.
Of the total group, 7 patients (28.0%) reported serious AEs (SAEs), none of which were considered related to trastuzumab treatment. Reported SAEs were pain, septic arthritis, erysipelas, lung cancer, fibula fracture, urinary tract infection, and a broken leg. There were no reports of cardiac SAEs, and there were no deaths during the study period.
The authors conclude that, in patients who received long-term treatment for their HER2-positive disease, trastuzumab had an acceptable safety profile and was well tolerated. “Stable LVEF outcomes and the absence of cardiac SAEs suggest that long-term [trastuzumab] therapy is feasible and without any additional cardiac safety risk, particularly with continued patient care and monitoring according to standard practice,” write the authors.
Müller V, Clemens M, Jassem J, et al. Long-term trastuzumab (Herceptin®) treatment in a continuation study of patients with HER2-positive breast cancer or HER2-positive gastric cancer. BMC Cancer. 2018;18:295. doi: 10.1186/s12885-018-4183-2.