Marking the first time an immunotherapy agent has been approved for the treatment of a form of breast cancer, the U.S. Food and Drug Administration (FDA) has authorized the use of the drug atezolizumab in combination with the chemotherapy drug nab-paclitaxel for patients with advanced triple-negative breast cancer.
The approval was granted on an accelerated basis following publication of the results of an international phase III trial that tested the drug combination in more than 900 women with the disease. The trial found that among participants whose tumor cells carried a particular molecular marker, the combination treatment produced better survival and disease-control rates than chemotherapy alone.
The trial, dubbed Impassion130, is part of a broad effort to determine whether drugs known as immune checkpoint inhibitors, which have had limited success on their own in patients with breast cancer, can be more effective when paired with other therapies. The trial focused on triple-negative breast cancer, an often aggressive disease that doesn’t respond to hormone therapy or to drugs that block the HER2 protein and accounts for about 15% of all breast cancer cases.
What is atezolizumab?
Atezolizumab is a checkpoint inhibitor that targets a protein called PD-L1 on tumor cells. The protein serves to hold back an immune system attack on cancer. By blocking it, drugs like atezolizumab allow such an attack to proceed.
Half of the participants in the trial were randomly assigned to receive atezolizumab in combination with nab-paclitaxel, and half received only nap-paclitaxel plus a placebo. About 41% of the participants had PD-L1 on their immune cells.
The investigators found that women whose tumors tested positive for PD-L1 and received the immunotherapy-chemotherapy combination had a median overall survival of 25 months, compared to 18 months for the chemotherapy-only group. The combination therapy also improved progression-free survival (PFS) — the length of time before the cancer worsened. Median PFS was 7.5 months for the combination group, compared to 5.0 months for the chemotherapy-alone group.
A similar proportion of patients in each group had adverse side effects. The incidence of immune-related toxicities was higher among patients receiving atezolizumab.
FDA approval of the combination therapy for patients with advanced triple-negative breast cancer has been practice-changing at Dana-Farber and other treatment centers.
“We have now started testing tumors of patients with triple-negative breast cancer to see if the cells carry the PD-L1 receptor. This helps us understand if giving immunotherapy is likely to be beneficial for these patients,” says Sara Tolaney, MD, MPH, a breast oncologist and associate director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber.
The results of the Impassion130 trial have spurred an array of trials to explore whether other immunotherapy-chemotherapy combinations work just as well or better than atezolizumab and nab-paclitaxel in this group of patients. These include a phase II trial of the chemotherapy agent carboplatin and the checkpoint inhibitor nivolumab and a trial of the oral chemotherapy agent tesetaxel in combination with atezolizumab, nivolumab, or pembrolizumab.
A patient perspective
First diagnosed in December 2013, Rita McGuire O’Brien’s triple-negative inflammatory breast cancer recurred soon after receiving preoperative chemotherapy and undergoing a mastectomy and six weeks of radiation treatments. The disease then progressed despite receiving two different regimens of chemotherapy.
O’Brien, who lives in Fall River, Mass., says that after the cancer recurred, she felt “depressed and not hopeful.” Then, while being treated at Dana-Farber, she met Tolaney, who told her about a new clinical trial for patients like her. The phase 1 study was testing a combination of immunotherapy and chemotherapy for triple-negative breast cancer. The rationale was that immunotherapy — which hadn’t yet shown effectiveness in breast cancer — might be spurred to greater potency by the addition of chemotherapy.
O’Brien began the combination trial in April of 2015 and is still in treatment. She comes to Dana-Farber once a week for three weeks, receiving nab-paclitaxel (chemotherapy) and atezolizumab, the immunotherapy antibody, and takes one week off.
Now almost four years later, the only remnant of her cancer is a small lymph node in her armpit that shows on scans.
Not everyone in the phase 1 trial she participated in has done as well, but even in this group of patients, with recurrent breast cancer, 39% of patients responded. Those encouraging results led to the phase 3 Impassion130 clinical trial.