Tecentriq (atezolizumab) is an immunotherapy approved by the U.S. Food and Drug Administration (FDA) in combination with nab-paclitaxel for people with locally advanced or metastatic triple-negative breast cancer (TNBC). The treatment combo, approved in March 2019, is used for patients whose tumors are positive for the programmed cell death-ligand 1 (PD-L1) protein, and cannot be removed surgically by doctors.
The combination therapy is the first regimen that the FDA approved for breast cancer to include an immunotherapy. The European Commission (EC) also approved the combination therapy, in August 2019, for the same subset of patients in the EU.
How does Tecentriq work?
The active component of Tecentriq is a fully humanized, genetically engineered monoclonal antibody against the PD-L1 protein. The antibody binds to PD-L1, which is highly expressed on a subset of breast cancer cells in TNBC. PD-L1 prevents immune cells called T cells from killing cancer cells by interacting with the PD-1 protein on T cells.
By blocking the interaction between PD-1 on T cells and PD-L1 on breast cancer cells, Tecentriq makes breast cancer cells more susceptible to being killed by T cells. That action, in turn, can slow or stop cancer cell growth and reduce the spread of cancer to other parts of the body, called metastasis.
Tecentriq in clinical trials
Researchers conducted a Phase 3, multicenter, double-blind, randomized trial (NCT02425891) involving TNBC patients with unresectable (not surgically removable) locally advanced or metastatic disease. Their aim was to determine the safety and efficacy of Tecentriq plus nab-paclitaxel.
The participants received treatment until they experienced disease progression or unacceptable levels of toxicity. The primary endpoints were progression-free survival (PFS) and overall survival (OS), as well as the number of patients who showed treatment-related adverse events.
The study’s results were reported in the New England Journal of Medicine. The median PFS for Tecentriq plus nab-paclitaxel was 7.2 months, compared with 5.5 months for the placebo plus nab-paclitaxel group. Similarly, the median OS for Tecentriq plus nab-paclitaxel was 21.3 months. It was 17.6 months for the placebo plus nab-paclitaxel group.
In patients with PD-L1–positive tumors, the median progression-free survival for those receiving Tecentriq plus nab-paclitaxel was 7.5 months, compared with five months for those receiving placebo plus nab-paclitaxel. Moreover, the median overall survival for patients with PD-L1-positive tumors was 25 months for those receiving Tecentriq plus nab-paclitaxel versus 15.5 months for those receiving placebo plus nab-paclitaxel.
The adverse events in both groups were similar. They included alopecia (hair loss), peripheral neuropathy (nerve problems), fatigue, nausea, diarrhea, anemia, constipation, cough, headache, neutropenia (low neutrophil counts), vomiting, and decreased appetite.
Treatment discontinuation because of adverse events occurred in 15.9% of the patients receiving Tecentriq plus nab-paclitaxel. It was 8.2% in those who received a placebo plus nab-paclitaxel.
Overall, Tecentriq plus nab-paclitaxel treatment showed an acceptable safety profile and significant improvement in PFS and OS. These results led to the FDA approval.
Ongoing clinical trials
There are many ongoing Phase 3 studies investigating Tecentriq in TNBC, including ones testing the medicine in early and advanced stages of the disease, and others assessing it with different combinatorial therapies.
One study, called IMpassion031 (NCT03197935), is investigating the use of Tecentriq plus nab-paclitaxel, followed by doxorubicin and cyclophosphamide, prior to surgery to remove tumors in people with early stage TNBC. Involving an estimated 324 patients, that trial is comparing the treatment group — which receives Tecentriq — with a placebo group that is given other treatments without Tecentriq. The goal of the study is to investigate the percentage of patients who reach pathological complete response (pCR), or no signs of cancer when they go for their surgery.
Genentech released information from the trial in July 2020. The data showed that more patients in the Tecentriq-treatment group achieved pCR in contrast with the placebo group. This was the case regardless of whether or not the tumor cells contained PD-L1.
Another study, called IMpassion131 (NCT03125902), is investigating the combination of Tecentriq plus paclitaxel, a different formulation than nab-paclitaxel, in patients with PD-L1-positive metastatic TNBC. Researchers in this study are comparing Tecentriq plus paclitaxel with placebo plus paclitaxel in roughly 600 patients.
An initial analysis found no significant difference between the groups in progression-free survival. The FDA released a statement on Sept. 8, 2020, saying that the results of the study show that paclitaxel is not a substitute for nab-paclitaxel in the treatment of PD-L1-positive metastatic TNBC and that the interim results actually show a negative effect of Tecentriq plus paclitaxel in overall survival compared with the placebo plus paclitaxel. The alert said health care professionals should not replace paclitaxel protein-bound with paclitaxel in clinical practice.
Doctors also can also use Tecentriq to treat patients with advanced-stage urothelial carcinoma, a type of bladder cancer, and non-small cell lung cancer (NSCLC) whose disease has spread and cannot be removed by surgery.
Last updated: Sept. 18, 2020
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