Immunotherapy Shows Promise for TNBC Patients
By MELANIE KILGORE-HILL
FDA Approves Tecentriq® as First Immunotherapy Regimen for Breast Cancer
A breakthrough therapy is offering unprecedented hope to women with metastatic triple negative breast cancer (TNBC).
Last month, the FDA granted Genentech, a member of the Roche Group, accelerated approval to Tecentriq® (atezolizumab) plus chemotherapy for the treatment of adults with unresectable locally advanced or metastatic TNBC in people whose tumors express the protein PD-L1. The Tecentriq combination is the first cancer immunotherapy regimen to be approved in breast cancer, which represents a giant step forward in the treatment of a historically difficult-to-treat form of the disease.
Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 271,000 people in the United States will be diagnosed with breast cancer, and more than 42,000 will die from the disease in 2019.
Erika Hamilton, MD
Erika Hamilton, MD, director of the Breast Cancer and Gynecologic Cancer Research Program at Sarah Cannon Research Institute and an IMpassion130 (Tecentriq) study investigator, said triple negative breast cancer, which accounts for 15 to 20 percent of breast cancers, is the most medically challenging to treat, partially because it tends to be more aggressive than more common types of the cancer.
Breast cancer can be diagnosed based on the presence or absence of three receptors - estrogen, progesterone and HER2. These receptors are the drivers for the development and growth of breast cancer. Triple negative breast cancer is diagnosed when a pathology report shows a negative result for all three of the common receptors.
While targeted therapies exist to decrease reoccurrence of hormonally-driven and HER2 breast cancers, patients with TNBC have historically received only chemotherapy. "The tricky thing about triple negative breast cancer is that we haven't had any targeted medications to treat it like we do for other types of breast cancer," Hamilton said.
"Triple negative is the worst prognosis, and women with metastatic TNBC typically have a survival rate of 18 months," she continued. "Biologically, it just tends to be more aggressive, and it's a more heterogeneous breast cancer group since all triple negatives aren't the same. They're a basket of cancers that don't express receptors, so it's been challenging to find a therapy that's effective for a large enough population."
Now, Hamilton and other oncologists are turning to atezolizumab - an immunotherapy already approved for treatment of certain lung and bladder cancers. Immunotherapy is a type of biological therapy that uses targeted drugs to convince the body's immune system to recognize that there is something foreign in the body (cancer) and to attack the cells threatening it.
Technically speaking, Tecentriq is a monoclonal antibody designed to bind with the protein PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells, which are essential for immunity.
During the Phase III IMpassion130 trial, which involved 902 participants, the IV therapy was administered in combination with the common chemotherapy drug nab-paclitaxel with notable results. Progression-free survival increased from 5 to 7.5 months, but what impressed Hamilton was that it translated into overall survival to a more significant degree.
The 41 percent of TNBC patients with the PD‑L1 protein, which helps cells hide from immune attack, extended life expectancy from 15.5 to 25 months. In fact, one TNBC trial participant under Hamilton's care is still working full-time three years after starting atezolizumab and no longer receives chemotherapy.
She said side effects of atezolizumab also make the therapy more appealing over chemo. "Day-to-day, it's tolerated really well, with no nausea or hair loss," Hamilton said, noting that some patients do experience fatigue or symptoms of immune activation, such as low-grade fever or body aches. "Compared to receiving chemo on a day-to-day basis, patients feel very good on it, and it's something you can stay on longer than chemo," she said.
A Genentech spokesperson said the company currently has several other large, ongoing studies of Tecentriq in TNBC, including early and advanced stages of the disease. In addition to Tecentriq, they're also studying the AKT-inhibitor ipatasertib in TNBC.