The addition of the targeted therapy onartuzumab to Taxol® (paclitaxel) with or without Avastin® (bevacizumab) does not appear to help control disease or improve survival in patients with metastatic triple-negative breast cancer. These findings were published in the Annals of Oncology.
The majority of breast cancers are hormone receptor-positive, meaning that the cancer cells are stimulated to grow from exposure to the female hormones estrogen and/or progesterone. Other breast cancers are referred to as HER2-positive, which means that they overexpress the human epidermal growth factor receptor 2, a biologic pathway that is involved in replication and growth of a cell.
Breast cancers, on the other hand, that are not stimulated to grow from exposure to estrogen or progesterone and do not overexpress HER2 (HER2 negative) are called triple-negative breast cancers. Triple-negative breast cancers tend to be more aggressive than other breast cancers and have fewer treatment options because hormonal therapies that target hormone receptors or HER2 are ineffective.
Because patients with triple-negative breast cancer have limited treatment options, finding effective therapies is an important area of research. In a recent study, researchers tested the combination of the investigational drug onartuzumab and the chemotherapy agent Taxol with or without the targeted therapy Avastin as treatment for triple-negative breast cancer. Onartuzumab is designed to target and inhibit a protein known as MET, which is associated with growth and spread of triple-negative breast cancer.
In a Phase II clinical trial, researchers tested the effectiveness of onartuzumab plus Taxol with or without Avastin in patients with metastatic triple-negative breast cancer. They enrolled 185 women in the study and divided them into three treatment groups: 60 patients received onartuzumab plus a placebo plus weekly Taxol; 63 patients received Avastin plus onartuzumab plus Taxol; and 62 patients received placebo plus Avastin plus Taxol.
The researchers’ main focus was to compare progression-free survival among the three treatment groups. They also measured overall survival, partial and complete response, and safety.
The addition of onartuzumab to treatment did not appear to benefit patients. Patients who received onartuzumab with Avastin plus Taxol did not have an improvement in progression-free survival. In addition, patients on onartuzumab plus weekly Taxol (without Avastin) had a higher risk that disease would get worse or progress than patients on Avastin and Taxol with onartuzumab. Patients who received Avastin (with onartuzumab and Taxol or with Taxol alone) had a higher rate of partial and complete responses. Patients who received onartuzumab plus Taxol with or without Avastin had a shorter median overall survival than patients in the Avastin-plus-Taxol (no onartuzumab) group.
The researchers also found that majority of patients in the study—88%—did not have tumors that expressed the protein MET. As onartuzumab targets MET, this may explain why the drug didn’t improve progression-free survival among study participants.
When it came to safety, researchers measured rates of peripheral edema (an accumulation of fluid that causes swelling, usually in the lower limbs). Patients who received onartuzumab (both with Avastin and Taxol or Taxol alone) had a higher incidence of peripheral edema than patients who received Avastin and Taxol without onartuzumab.
Based on these findings, the addition of onartuzumab to Taxol alone or Taxol plus Avastin does not appear to improve survival for patients with triple-negative breast cancer that doesn’t express MET. Furthermore, the addition of onartuzumab appeared to raise the risk of peripheral edema.
Reference: Diéras V, Campone M, Yardley DA, et al. Randomized, phase II, placebo-controlled trial of onartuzumab and/or bevacizumab in combination with weekly paclitaxel in patients with metastatic triple-negative breast cancer. Annals of Oncology. 2015 September;26(9):1904-10. doi: 10.1093/annonc/mdv263.