FDA Grants Accelerated Approval to Tecentriq-Abraxane Combo for Some TNBC

FDA Grants Accelerated Approval to Tecentriq-Abraxane Combo for Some TNBC

The U.S. Food and Drug Administration has granted accelerated approval to a combination of Tecentriq (atezolizumab) and the chemotherapy Abraxane (nab-paclitaxel) for patients with advanced triple-negative breast cancer, making this the first immunotherapy regimen approved specifically for breast cancer.

The approval, which is for patients whose tumors produce the PD-L1 factor and are unable to receive surgery, was based on data from the IMpassion130 Phase 3 trial (NCT02425891), where the combination cut the risk of death or disease worsening by 40% compared to Abraxane only.

Continued approval of this Tecentriq combination, like most accelerated approvals, is contingent on additional data confirming that the approach also brings overall survival benefits.

The agency also approved the Ventana PD-L1 Assay as a companion diagnostic device for selecting triple-negative breast cancer eligible for the combination treatment.

“The FDA approval of this Tecentriq combination is an important treatment advance for people with PD-L1-positive, metastatic triple-negative breast cancer, a disease with high unmet medical need,” Sandra Horning, MD, chief medical officer and head of global product development, said in a press release. “This Tecentriq combination is the first cancer immunotherapy regimen to be approved in breast cancer, representing a meaningful step forward in the understanding of this disease.”

Tecentriq, developed by Genentech, is an immune checkpoint inhibitor meant to block signals from cancer cells that impair the immune system from doing its job. It binds to the PD-L1, produced by cancer cells, and prevents its binding to the PD-1 receptor on immune cells. It is approved for some patients with bladder or non-small cell lung cancer.

Abraxane is a kind of injectable nanoparticle in which the chemotherapy paclitaxel is bound to the protein albumin, which works as a delivery vehicle. The approach is a standard chemotherapy for patients with metastatic breast cancer, also approved for metastatic non-small cell lung cancer and pancreatic cancer.

The combination of both treatments was tested in IMpassion130, an international, multi-center, randomized, double-blind Phase 3 study. The study included 902 patients across 41 European countries, the United States, Canada, Asia, Latin America, and Australia.

Participants were randomly assigned Tecentriq or a placebo — given every two weeks — along with weekly Abraxane chemotherapy at a schedule of three weeks on, one week off. Treatment was administered until patients experienced signs of disease progression or toxicity.

IMpassion130’s main goals were to determine whether Tecentriq extended overall survival and delayed disease progression or death both in the overall population and in the subset of patients whose tumors produced the PD-L1 factor — a predictor of response to Tecentriq.

Secondary measures included overall response rate, duration of response, and time to quality of life deterioration.

In the entire study population, Tecentriq extended the median time to disease progression or death from 5.5 to 7.2 months. The combination also prolonged median overall survival from 17.6 to 21.3 months, but the difference did not reach statistical significance.

The treatment, however, showed particularly better survival outcomes in patients with PD-L1-positive tumors. In this subgroup, patients on Tecentriq lived without disease worsening for a median of 7.5 months, compared to five months on Abraxane only. Similarly, the median survival was 25 months, nearly 10 more months that those on chemotherapy only.

The Tecentriq combination also led to a higher number of patients showing tumor shrinkage compared to the control group — 56.0% vs. 45.9%.

Again, this effect was more pronounced in the PD-L1-positive group, where 58.9% of patients given Tecentriq saw their tumors shrink, compared to 42.6% in the Abraxane group.

The combo treatment was well-tolerated without any unexpected adverse effects, researchers said. Serious adverse effects were detected at similar rates between the Tecentriq (23%) and the Abraxane groups (18%), and included mostly low levels of certain blood cells, tingling sensation in the hands or feet, fatigue, low potassium, pneumonia, and higher levels of liver enzymes.

These side effects were consistent with the toxic effects of Tecentriq and Abraxane known from prior studies.

“The Tecentriq regimen is an exciting new treatment option for certain people living with metastatic triple-negative breast cancer, a difficult-to-treat form of the disease,” said Hayley Dinerman, executive director of the Triple Negative Breast Cancer Foundation. “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.”