Update: On March 8, 2019, the US Food and Drug Administration approved the combination of atezolizumab (Tecentriq®) and nab-paclitaxel (Abraxane®) as a first-line treatment for people with triple-negative breast cancer that expresses the PD-L1 protein and cannot be removed completely with surgery.
Original story: At the annual meeting of the European Society for Medical Oncology, an international team of breast cancer experts reported findings from a large clinical trial. They had tested a combination of immunotherapy and chemotherapy in people with advanced triple-negative breast cancer. The investigators found that many people in the study who had the immunotherapy combination therapy lived longer compared with chemotherapy alone.
Memorial Sloan Kettering medical oncologists Elizabeth Comen and Christopher Klebanoff, both experts in breast cancer immunotherapy, spoke about the findings and the potential impact on the field. Neither Dr. Comen nor Dr. Klebanoff were part of the study, which was published in the New England Journal of Medicine.
A Focus on Triple-Negative Breast Cancer
“Triple negative” means that tumor growth is not driven by any of the three most common proteins known to fuel breast cancer: the estrogen receptor, the progesterone receptor, and the HER2 receptor. Triple-negative breast cancer is also difficult to treat.
“There is a tremendous unmet medical need in this breast cancer subtype,” Dr. Klebanoff says. “We’ve made great progress in recent years in treating other types of breast cancer, but triple-negative breast cancer has not benefitted from many advances.”
“Immunotherapy works best on solid tumors that have large numbers of mutations because mutations put up flags that make the tumors visible to the immune system,” Dr. Comen adds. “It’s long been thought that triple-negative breast cancers might be susceptible to immunotherapy because they tend to have a lot more mutations that the immune system can recognize.”
The trial included 902 people who were treated at 246 hospitals in 41 countries. All of them had locally advanced or metastatic triple-negative breast cancer. The people in this study were given one of three treatments: a standard chemotherapy drug for this type of breast cancer called nab-paclitaxel (Abraxane®); an immunotherapy drug already approved for other cancers called atezolizumab (Tecentriq®), which works against the protein PD-L1; or a combination of the two.
The researchers reported that people with tumors that expressed the PD-L1 protein who received the combination therapy lived 9.5 months longer. About 41% of people in the trial had this protein on their tumors. “This is not a cure, and at every step of the way we’re always looking for that,” Dr. Comen says. “But any incremental benefit to patients’ lives can be significant, and this is a significant benefit.”
“This study dispels the myth that immunotherapy cannot work for breast cancer,” Dr. Klebanoff says. “As we learn more about this approach, we expect to see more and better treatment options for many breast cancer patients.”
“A lot of the early successes in applying immunotherapy to treat solid tumors used a single drug that was able to take advantage of the immune system’s ability to recognize and kill cancer,” Dr. Klebanoff explains. “While this worked well for a few kinds of cancer, like lung cancer and melanoma, for most other types, including breast cancer, the results have been disappointing. Now there’s a second wave of studies. These are looking at combining immunotherapy with other treatments — chemotherapy, targeted therapy, radiation therapy, or even multiple immunotherapies at the same time. We’re learning that there can be a synergistic effect, that the combination treatments produce results that are much greater than their individual parts.”
Effects on the Standard of Care
“For some people with triple-negative breast cancer — those whose tumors express PD-L1 — this study is probably going to change how many of them are treated,” Dr. Comen says. “But we can’t assume a one-size-fits-all approach.”
“We still don’t know much about the side effects that were seen in this trial, and it’s important to learn more,” Dr. Klebanoff says. “Immunotherapies are not without toxicities, so we’ll need to be precise in determining who will truly benefit.”
Immunotherapy Trials for Breast Cancer at MSK
MSK has a robust portfolio of breast cancer clinical trials evaluating the use of immunotherapy, not only triple-negative disease but other types as well. One trial being led by Drs. Comen and Klebanoff is looking at a number of immunotherapy combinations in women with estrogen receptor-positive, HER2-negative tumors. That trial is currently recruiting patients. Another trial being led by Dr. Klebanoff and MSK medical oncologist Shanu Modi is looking at an immunotherapy for women with HER2-positive cancer.
Finally, Dr. Klebanoff is also conducting research on a different kind of immunotherapy: using genetically engineered T cells to track down and kill cancer cells.
“Our trials range from early-stage phase I trials to large phase III trials,” he says. “We’re delighted to see any patient who has an interest in immunotherapy for breast cancer and who wants to find out if a clinical trial makes sense for them.”