FDA Grants Accelerated Approval to Immunotherapy for Advanced Triple-Negative Breast Cancer

Atezolizumab lengthened the time before cancer grew in first positive trial results for immunotherapy in breast cancer
Breast Cancer News
April 3, 2019
Eric Fitzsimmons, Copy Editor and Content Coordinator
Reviewed By: 
Rita Nanda, MD

The Food and Drug Administrationinfo-icon granted accelerated approval for atezolizumab (Tecentriq) to treat people with metastaticinfo-icon triple-negative breast cancerinfo-icon and stageinfo-icon III triple-negative breast cancer that can’t be removed with surgeryinfo-icon. The cancer must test positive for the PD-L1 proteininfo-icon. The approval was announced by atezolizumab’s maker, Genentech, on March 8.

The approval was based on a randomized, phase III study published in October 2018, in the New England Journal of Medicineinfo-icon. When atezolizumab was added to treatment with the chemotherapyinfo-icon nab-paclitaxelinfo-icon (Abraxaneinfo-icon), atezolizumab, on average, kept the cancer from growing for a longer time. Atezolizumab is the first PD-L1 targeting medicine approved for breast cancer.


Triple-negative breast cancer is a type of breast cancer type that does not grow in response to the hormones estrogeninfo-icon or progesteroneinfo-icon and does not express too much of the HER2 protein. Because of this, there are currently no targeted therapies available to treat triple-negative breast cancer. Until now, the only approved treatment was chemotherapy.

Atezolizumab is an immunotherapyinfo-icon. It works by blocking the PD-L1 protein. PD-L1 expression in a tumorinfo-icon can cause certain immune cells that attack cancer, known as T cells, to become inactive. Atezolizumab can help to “switch on” these cells. Atezolizumab is already approved by the FDAinfo-icon to treat a type of bladder cancer and non-small cellinfo-icon lung cancer.

The IMpassion130 Trial

The phase III IMpassion130 trial compared the combination of atezolizumab and nab-paclitaxel chemotherapy to chemotherapy alone. Researchers wanted to see if adding atezolizumab to standard treatment would allow people with metastatic and certain stage III triple-negative breast cancers that can’t be treated with surgery to go longer without the cancer growing.

Researchers also looked at whether people taking atezolizumab would live longer overall. Researchers found that participants who had tumors that expressed the PD-L1 protein were the ones who benefited from adding atezolizumab to chemotherapy. Those whose tumors did not express the PD-L1 protein did not appear to benefit from the addition of atezolizumab to chemotherapy.

IMpassion130 randomly assigned 902 people, some with metastatic triple-negative breast cancer and some with stage III TNBC that could not be removed with surgery, to be given either

  • atezolizumab and nab-paclitaxel, or
  • placeboinfo-icon and nab-paclitaxel

No participants had chemotherapy or targeted therapyinfo-icon to treat metastatic or advanced breast cancer before the study. They were allowed to have had chemotherapy and radiationinfo-icon for early-stage breast cancerinfo-icon, but only if they had completed treatment at least 1 year before joining the study. Participants stayed on their assigned treatment until the breast cancer grew or they experienced unacceptable side effects. 

Researchers measured the success of atezolizumab by how long people went after treatment started without the cancer growing, called progression-free survivalinfo-icon, and how long they lived after the start of treatment, called overall survival.

Progression-Free Survival

Adding atezolizumab improved progression-free survival. The result was statistically significantinfo-icon, meaning it was not likely to be the result of chance. The average time people went without the cancer growing was

  • 7.2 months if they were given nab-paclitaxel with atezolizumab
  • 5.5 months if they were given nab-paclitaxel with a placebo

The study also looked specifically at the progression-free survival of trial participants with cancer that tested PD-L1 positive. Of all participants, 40.9 percent had cancer that tested positive for the PD-L1 protein. The progression-free survival in this PD-L1-positive subgroup was also significantly longer with atezolizumab treatment compared to those given placebo. The medianinfo-icon was

  • 7.5 months for people given nab-paclitaxel and atezolizumab
  • 5.0 months for people given nab-paclitaxel and placebo

Overall Survival

The study findings also included the first analysis of overall survival, how long people lived after enrolling in the study. The average overall survival was longer in the atezolizumab group than in the placebo group, but it was not statistically significant. This means the result was not different enough between groups or there wasn’t enough data to prove the difference wasn’t by chance.

For people with cancer that tested PD-L1-positive, researchers found that adding atezolizumab appeared to help them live longer:

  • People in the atezolizumab group had a median overall survival of 25 months.
  • People in the placebo group had a median overall survival of 15.5 months.

Side Effects

The atezolizumab group had more reports of nauseainfo-icon, cough, low white blood cellinfo-icon counts and hypothyroidism, a conditioninfo-icon where the thyroid doesn’t make enough of a certain hormoneinfo-icon, than the chemotherapy alone group. People in the atezolizumab group were also more likely to have side effects severe enough to interfere with daily activities:

  • 48.7 percent of people in the atezolizumab group reported severe effects
  • 42.2 percent of people in the placebo group reported severe side effects

PD-L1 and the San Antonio Breast Cancer Symposium

Further results from this trial were shared in December at the 2018 San Antonio Breast Cancer Symposium. These findings focused on looking at PD-L1 expression on immune cells within the tumor to tell who might benefit from adding atezolizumab to treatment. The analysis found that PD-L1 expression on those immune cells was the best way to predict if atezolizumab would improve the effect of treatment. People with cancer that tested PD-L1 positive went longer without cancer growing and appeared to live longer overall. Breast cancer that did not express PD-L1 saw no change from the addition of atezolizumab.

What This Means for You

The approval of a new treatment is exciting for people with triple-negative breast cancer, a subtype that has few treatment options outside of chemotherapy. The FDA announced in November that it granted atezolizumab priority review based on the results from IMpassion130 and granted it accelerated approval in March. These FDA approval programs are for medicines that seem to significantly improve the treatment of a serious condition and allow the drug applications to get an approval decision more quickly than they would under the standard FDA schedule. Accelerated approval makes atezolizumab available to the public faster than the normal approval process would take. It was granted because trials show the medicine is safe and helps people go longer without the cancer getting worse. The approval makes atezolizumab available for treatment, but it will continue to be studied in trials to see if it improves overall survival, how long people live after starting treatment.

This is the first approval for atezolizumab in breast cancer, so depending on the details of your diagnosisinfo-icon, it may not be an option for you right now. This approval is also the first in breast cancer that uses PD-L1 as a target for treatment. If you think you may be eligible for atezolizumab, your doctor will have to test for PD-L1 expression.

Genentech, has several other studies ongoing to find other cases where atezolizumab can be used in early-stage and metastatic triple-negative breast cancer.


Schmid, P, Adams, S, Rugo, H, et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. New England Journal of Medicine. November 29, 2018; 379:2108-2121. DOI: 10.1056/NEJMoa1809615

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