SABCS 2014: Immunotherapy Shows Early Promise for Triple-negative Breast Cancer Patients

After making great strides for some patients with melanoma and lung cancer, immunotherapy drugs are starting to offer hope for women with a very challenging form of breast cancer—triple-negative breast cancer.

Data presented Dec. 10 at the San Antonio Breast Cancer Symposium showed that the PD-1 inhibitor pembrolizumab (Keytruda) was well tolerated by women with recurrent or metastatic triple-negative breast cancer and showed early signs of effectiveness. The PD-L1 inhibitor MPDL3280A was also found to be safe and tolerable for women with metastatic triple-negative breast cancer, with tumor shrinkage in some women.

Pembrolizumab Trial

Rita Nanda, MD, speaks about a phase I trial of pembrolizumab in patients with advanced triple-negative breast cancer during a news conference Dec. 10 at the San Antonio Breast Cancer Symposium. Photo by Scott Morgan.
Rita Nanda, MD, speaks about a phase I trial of pembrolizumab in patients with advanced triple-negative breast cancer during a news conference Dec. 10 at the San Antonio Breast Cancer Symposium. Photo by Scott Morgan.

This phase I, nonrandomized multicenter trial involved 32 patients from 29 to 72 years old who had heavily pretreated recurrent or metastatic triple-negative breast cancer. Patients received intravenous infusions of pembrolizumab every two weeks. Safety and tolerability of the drug—the standard endpoints of a phase I trial—were assessed, as well as antitumor activity.

Of the 27 patients with sufficient data for analyses, one patient had a complete response (CR), four had a partial response (PR), seven had stable disease, and 12 had progressive disease. Three patients discontinued therapy as their tumors progressed. One patient with a CR and two patients with a PR continue to be treated with pembrolizumab.

“The promising activity of pembrolizumab seen in PD-L1-expressing triple-negative breast cancer is very exciting and certainly worthy of further investigation,” says oncologist and lead investigator Rita Nanda, MD, who is an assistant professor of medicine and the associate director of the Breast Medical Oncology Program at the University of Chicago.

MPDL3280A Trial

In a multicenter phase I trial testing MPDL3280A, triple-negative breast cancer patients from 29 to 72 years old whose tumors were found to have the PD-L1 protein were enrolled. Of the 12 patients who received the drug and for whom there were sufficient data for analysis of safety, most had received at least two prior therapies. Patients received intravenous injections of MPDL3280A every three weeks for up to one year.

Of the nine patients who could be evaluated for efficacy, one patient had a CR and two had a PR. One patient had stable disease. All of these responses occurred within six weeks of receiving the first dose of the drug.

How Drugs Targeting PD-1 Work

Our immune system is naturally capable of defending us against cancer. However, cancer cells play many tricks to escape an immune system attack. For example, when proteins called programmed death-ligands 1 and 2 (PD-L1 and PD-L2) are present on tumor cells and bind to the programmed death-1 (PD-1) protein that is present on some immune cells, called T cells, “brakes” are applied on these T cells that prevent them from attacking the tumor cell.

The two drugs discussed here are designed to release these brakes: Pembrolizumab binds to PD-1 on T cells and prevents its interaction with PD-L1 present on the tumor cells. MPDL3280A binds to PD-L1 and prevents its interaction with PD-1 on T cells. With the brakes released, the T cells can eliminate the tumor cells.

The U.S. Food and Drug Administration approved pembrolizumab in September 2014 for the treatment of certain patients with metastatic melanoma, the most deadly form of skin cancer. This drug is also being tested for non–small cell lung cancer in early clinical trials.

Identifying the Right Patients Is Key

While these studies shows promise, identifying the right breast cancer patients for immunotherapy is key, notes breast cancer specialist and AACR President Carlos L. Arteaga, MD, co-chair of the meeting and director of the Breast Cancer Program at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. “The data with these early trials are promising, but there are some challenges. We still don’t know whom to treat,” says Arteaga, who was not involved in either of the clinical trials. “As we make progress in identifying breast cancer patients who are going to benefit from immunotherapy, we will have an entirely new type of treatment approach added to the armamentarium of breast cancer therapies.”

A study published in Nature in November showed that MPDL3280A was effective against a variety of cancer types that manage to suppress an immune attack via the PD-1/PD-L1 mechanism. With information accumulating on better ways to identify patients who might benefit from immunotherapy, we seem to be heading in the direction Arteaga hopes for.

“Triple-negative breast cancer is an area of active research,” says Nanda. “We are learning more about the different subtypes and are working hard to develop targeted approaches for patients with all forms of this disease. I would encourage patients with triple-negative breast cancer to consider enrolling in clinical trials if possible, so that together we can advance our understanding of these tumors and improve outcomes for women with this form of breast cancer.”

Breast cancer survivor and advocate Carol Simmons says, “It was nice to learn that the researchers are looking beyond the regular treatment regimens for breast cancer for possibilities.” She adds, “What better way to fight cancer than using your own immune system?”

After extensively researching her diagnosis of late-stage breast cancer in 2007 and her treatment plan, Simmons says she decided to start advocating for better care and new treatments for breast cancer patients. “I expect to learn a great deal at the symposium that will inform my work with the UCSF Breast Science Advocacy Core and researchers,” she adds.

This post is adapted from an article on the website of Cancer Today, a quarterly magazine for cancer patients, survivors, and caregivers published by the AACR. Read all of Cancer Today’s SABCS coverage.

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