by Dr. C.H. Weaver M.D. updated 6/2019
The US Food and Drug Administration granted accelerated approval to Tecentriq (atezolizumzb) in combination with Abraxane (nab-paclitaxel) for the first-line treatment of unresectable locally advanced or metastatic triple-negative breast cancer. (TNBC).
Tecentriq is the first immunotherapy to be approved for breast cancer.
The combination of Tecentriq immunotherapy and chemotherapy improve survival of women with TNBC as evidenced by the results from the IMpassion 130 clinical trial which were shared at the European Society for Medical Oncology (ESMO) 2018 Congress, published in the New England Journal of Medicine, and updated at the American Society of Clinical Oncology ASCO) meeting in June 2019.(1-3)
Approximately 15 percent of breast cancers are referred to as TNBC. Triple negative breast cancers are both hormone-negative, and HER2-negative. Hormone-negative breast cancer refers to a type of breast cancer that is both estrogen- and progesterone-receptor negative. This means that this type of cancer is not stimulated to grow from exposure to the female hormone estrogen and/or progesterone.
Breast cancers are referred to as human epidermal growth factor receptor (HER) 2-negative when they don't express HER2 receptors. HER2-positve cancers have a gene mutation that causes extra HER2 receptors to be present on the cell surface. Since the HER2 pathway is involved in cellular growth and replication, excessive HER2 receptors result in uncontrolled replication and spread of the HER2-positive cancer cells. HER2-negative breast cancer refers to cancer that does not have a mutated HER2 pathway, and therefore, is not stimulated to replicate and spread through the activity of excessive HER2 receptors.
Standard treatment for TNBC typically consists of surgery, chemotherapy and/or radiation therapy. However, optimal chemotherapy regimens for TNBC have not been determined.
About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death-ligand 1), which is expressed on cancer cells and cancer-infiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this interaction, Tecentriq enables the activation of T cells, restoring their ability to effectively detect and attack cancer cells.
Over 900 women with previously untreated advanced TNBC were enrolled on the IMpassion130 clinical trial and treated with Nab Paclitaxel chemotherapy with or without Tecentriq immunotherapy and directly compared.(1)
Overall the addition of Tecentriq improved the “progression free survival” by 20%. When the researchers looked at a subgroup of patients who were PD-L1+, the addition of Tecentriq improved PFS by 38% and increased overall survival by the same percentage, offering patients an additional 10 months of life over those who received chemotherapy alone.
ASCO 2019 Update Confirms Tecentriq Benefit in TNBC
Findings from the 2nd interim analyses were presented at the 2019 ASCO Annual Meeting and confirmed the clinically meaningful overall survival benefit for Tecentriq plus nab-paclitaxel in treatment-naïve patients with PD-L1–positive, metastatic triple-negative breast cancer.
Dr Schmid and his co-investigators confirmed there is a 10 month improvement in the average overall survival in PD-L1–positive patients. In 451 women with metastatic TNBC and PD-L1–positive cancers, the median overall survival was 25 months among patients with PD-L1–positive tumors compared to 15.5 months for treatment with Nab Paclitaxel alone.(2,3)
Other studies have suggested that PD-L1 may be a suitable target in TNBC as the protein can inhibit anti-cancer immune responses and it is expressed on tumor-infiltrating immune cells in patients with the disease.
According to the study authors in order “to improve the results of IMpassion130 further, the patient population needs to be better selected for those who are likely to benefit from immunotherapy the most. This means not just looking at PD-L1 expression, but also surrogates of immune response, tumor mutation burden, and microsatellite instability status, all of which have been observed to be altered in triple negative breast cancer patients.”
- European Society for Medical Oncology (ESMO) 2018 Congress. Presented October 20, 2018. Abstract LBA1.
- N Engl J Med. Published on October 20, 2018. Abstract
- Schmid P, Adams S, Rugo HS, et al. IMpassion130: updated overall survival (OS) from a global, randomized, double-blind, placebo-controlled, Phase III study of atezolizumab (atezo) + nab-paclitaxel (nP) in previously untreated locally advanced or metastatic triple-negative breast cancer (mTNBC). Presented at: the 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 1003.