The Food and Drug Administration (FDA) has approved the checkpoint blocker Tecentriq (atezolizumab) in combination with Abraxane (nab-paclitaxel) as a first-line treatment for people with locally advanced or metastatic triple-negative breast cancer who test positive for a response biomarker known as PD-L1.

“Chemotherapy alone has been the mainstay of treatment for many years, so it’s encouraging to now have an immunotherapy combination available for people with PD-L1-positive disease,” Hayley Dinerman of the Triple Negative Breast Cancer Foundation said in a Genentech press release.

This accelerated approval was based on by findings from the Phase III IMpassion130 trial, which showed that the combination improved progression-free survival, meaning patients were still alive without worsening of disease, by about two months. Most of the benefit appeared in the subgroup with PD-L1 positive tumors. Overall survival also may be longer with Tecentriq, but these data are still immature.

Tecentriq is a PD-L1 checkpoint inhibitor, a type of immunotherapy that unleashes T cells to attack cancer. It was previously approved for bladder and non-small-cell lung cancer. Tecentriq is given by IV infusion on days 1 and 15 of a monthly cycle. For breast cancer, it should be combined with Abraxane, a protein-bound formulation of the widely used chemotherapy drug paclitaxel that is less likely to cause hypersensitivity reactions.

PD-1 is an immune checkpoint, a receptor on T cells that plays a role in regulating immune function. Some tumors can hijack PD-1 to turn off immune responses against them. Drugs that block the interaction between PD-1 and PD-L1, its binding partner, can release the brakes and restore T-cell activity. This kind of immunotherapy works best against “hot” tumors that attract T cells. Checkpoint blockers alone have not shown much activity against “cold” breast tumors, but combining them with chemotherapy shows greater promise.

The IMpassion130 study included 902 participants—including a few men—with triple-negative breast cancer (TNBC). A majority of breast cancer carries estrogen or progesterone receptors, making it susceptible to hormone therapy. Other tumors express HER2 and can be treated with targeted drugs like Herceptin (trastuzumab). TNBC doesn’t express any of these receptors and is more difficult to treat. Accounting for about 15 percent of breast cancers, TNBC is more aggressive and is more common among young women, Black women and people with BRCA mutations.

Study participants had either locally advanced disease that could not be surgically removed or metastatic cancer that had spread elsewhere in the body, most often the lungs, bones or liver. They had not yet been treated for advanced cancer, though many had previously received presurgery (neoadjuvant) or postsurgery (adjuvant) therapy for earlier-stage breast cancer. Just over 40 percent were classified as PD-L1 positive, meaning at least 1 percent PD-L1 expression. They were randomly assigned to receive either Tecentriq or a placebo in combination with Abraxane.

The study results were presented at the European Society for Medical Oncology Congress last October and published in The New England Journal of Medicine.

Researchers reported that the overall response rate, meaning complete or partial tumor shrinkage, was 56 percent in the Tecentriq group and 46 percent in the placebo group; about 7 percent and 2 percent, respectively, had complete remission. Among people with PD-L1 positive tumors, the corresponding response rates were 59 percent and 43 percent.

In entire study population, the median progression-free survival (PFS) was 7.2 months with Tecentriq and 5.5 months with the placebo—a 20 percent reduction in the risk of disease progression or death. In the subgroup with PD-L1 positive tumors, the difference was 7.5 versus 5.0 months—a 38 percent improvement. In this group, 29 percent of Tecentriq recipients and 16 percent of placebo recipients were alive without disease progression after one year.

Overall survival results are preliminary because a majority of patients were still alive. The interim median overall survival was 21.3 months in the Tecentriq group and 17.6 months in the placebo group. For PD-L1 positive people, the difference was 25.0 versus 15.5 months.

“Immune therapy on top of standard chemotherapy prolonged survival by 10 months in patients with tumors expressing PD-L1,” lead researcher Peter Schmid, MD, PhD of Queen Mary University of London concluded. “This combination should become a new treatment option for patients with metastatic triple negative breast cancer.”

 

But other experts expressed skepticism.

 

“I have always believed that improvements in progression-free survival can have independent value for patients, even when there is not an overall survival benefit,” said Kathy Miller, MD, of Indiana University Simon Cancer Center in Indianapolis. “But for me, a two-month improvement in PFS with the cost and toxicity associated with immunotherapy isn’t worthwhile.”

 

Tecentriq plus Abraxane was found to be generally safe, but it often causes side effects. The most common adverse events include hair loss, peripheral neuropathy (nerve damage), fatigue, gastrointestinal symptoms, decreased appetite and neutropenia (loss of white blood cells that can raise infection risk). Checkpoint inhibitors can cause an overactive immune response that harms healthy organs including the lungs, liver, intestines and hormone-producing endocrine glands.

The study is ongoing and Genentech said more results will be presented at an upcoming conference. This FDA can withdraw approval if follow-up findings fail to show clinical benefits over the longer term.

Click here to read a Genentech press release about the approval.

Click here for full prescribing information for Tecentriq.