While immunotherapy has brought an impressive new option to several types of cancer, drugs that harness the immune system to fight cancer haven’t shown a significant benefit in treating breast cancer—until now.
According to a new clinical trial report, published in The New England Journal of Medicine, a combination of chemotherapy and immunotherapy achieved better outcomes than chemotherapy alone in women with advanced triple-negative breast cancer—a particularly hard-to-treat form of the disease. The combination that included the immunotherapy drug improved both progression-free survival and overall survival rates for women with a subtype of previously untreated triple- negative metastatic disease.
Triple-negative breast cancer—which doesn’t respond to drugs that block estrogen, progesterone, or over-expression of the HER2 gene—accounts for about 15 percent of breast cancer cases.
The researchers conducting the Impassion130 trial say that the combination should become a new treatment option for some women with metastatic breast cancer. The specific group of patients who benefited in this trial had so-called PD-L1 positive triple-negative disease, meaning their tumor-infiltrating immune cells were being restrained by the PD-L1 “checkpoint” molecular brake.
The phase 3 clinical trial, whose results were also discussed at the recent meeting of the European Society for Medical Oncology in Munich, included 902 women with this diagnosis. Half were randomly assigned to receive an immunotherapy drug, atezolizumab (Tecentriq), plus a chemotherapy agent, nab-paclitaxel. The other group received only nap-paclitaxel plus a placebo.
Atezolizumab is a checkpoint inhibitor antibody drug that releases a molecular brake on immune cells. This brake suppresses the immune response against cancer. Atezolizumab specifically targets the PD-L1 molecular brake present on immune cells that have infiltrated the breast tumor. In the clinical study patients, about 41 percent were found to have high levels of PD-L1.
Women whose tumors tested positive for PD-1 and received the immunotherapy-chemotherapy combination experienced a median overall survival of 25 months, versus 15.5 months for the chemo-only group.
The immunotherapy-chemotherapy combination also improved progression-free survival (PFS)—the length of time before the cancer worsened. Median PFS in the combination group was 7.3 months versus 5.5 months in the chemo-only patients.
A similar proportion of patients in each treatment group had adverse events. The type and severity of those adverse events were similar in the groups.
The trial was supported by F. Hoffman-La Roche.
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 Sara Tolaney, MD, MPH, a breast oncologist and associate director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber.
Tolaney 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.
More than three years later, the only remnant of her cancer is a small lymph node in her armpit that shows on scans, “and it’s not clear if this has active cancer in it or not at this time,” says Tolaney.
“I’m very grateful, and will never again give up hope,” says O’Brien. In December, it will be five years since her initial diagnosis—a very good outcome for patients with triple-negative breast cancer.
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 percent of patients responded, and the median survival rate was nearly 15 months. Those encouraging results led to the phase 3 Impassion130 clinical trial of nab-paclitaxel and atezolizumab as an upfront, initial therapy in triple-negative breast cancer.
“This regimen will likely receive Food and Drug Administration approval as first-line therapy for some patients with triple-negative breast cancer,” says Tolaney.