Jan. 29, 2018:

Breast cancer researchers have made great strides in recent years, identifying distinct molecular subtypes of the disease and potential novel treatment approaches. One such approach involves a type of immunotherapy, called an immune checkpoint inhibitor, that can help the immune system recognize and kill cancer cells.

Pictured from left: Kim Hirshfield, MD, PhD; Deborah Toppmeyer, MD; Nancy Chan, MD

Immune checkpoint inhibitors have shown promising results in a variety of research studies, and have been approved by the U.S. Food and Drug Administration to treat a variety of other cancers.

In breast cancer research, much attention has been focused on triple-negative disease, or cancers in which the three most common receptors that fuel breast cancer growth – estrogen receptor, progesterone receptor, and the HER2/neu gene – are not present. A number of studies are now testing checkpoint inhibitors in triple negative breast cancer.

“But sometimes we get so focused on one subgroup, that we forget about the hormone-positive breast cancers,” said Deborah L. Toppmeyer, MD, of the Rutgers Cancer Institute of New Jersey. Toppmeyer noted there is data that suggests checkpoint inhibitors could be potentially useful in hormone receptor positive (HR+) breast cancers as well.

To test this hypothesis, researchers at the Rutgers Cancer Institute of New Jersey are leading a new Big Ten Cancer Research Consortium study testing the immune checkpoint inhibitor pembrolizumab with fulvestrant, a type of hormone therapy called an estrogen receptor downregulator, in patients with advanced or metastatic HR-positive, HER2-negative breast cancer. Toppmeyer is co-investigator on the study, along with co-principal investigators Nancy Chan, MD, and Kim M. Hirshfield, MD, PhD, also of the Rutgers Cancer Institute of New Jersey.

“The objective of the study is to first make sure the combination of pembrolizumab with fulvestrant is safe. Both drugs are already FDA-approved, but the combination of the two has not been studied yet,” said Dr. Chan. “And secondly, we’re looking at whether the combination improves progression-free survival. Are we making a difference in these patients’ lives? Are we able to give them a longer period of time without cancer?”

The single arm, phase II study, known as BTCRC-BRE16-042, will enroll up to 47 subjects who have received no more than two lines of prior hormonal therapy or two lines of prior chemotherapy for advanced/metastatic disease. All participants will receive pembrolizumab every 21 days plus fulvestrant every 28 days.

About the Study Drugs

An important job of the immune system is to distinguish between normal cells in the body and those it sees as “foreign.” This tells the immune system to attack the foreign cells while leaving the normal cells alone.

PD-1 is a checkpoint protein on immune cells called T cells. It normally acts as an “off switch” that keeps the T cells from attacking other cells in the body. PD-1 attaches to another protein called PD-L1 found on some normal (and cancer) cells. When this happens, it tells the T cells to leave the other cell alone. Some cancer cells have lots of PD-L1, which helps them avoid an immune attack.

Pembrolizumab is an immunotherapy that blocks the PD-1 pathway. By blocking PD-1, it allows the immune system to recognize and kill cancer cells.

Many breast cancers have estrogen receptors and the growth of the tumors can be fueled by estrogen. Fulvestrant is a drug that blocks the estrogen receptor site. This prevents tumor growth and reproduction.

Pembrolizumab (also known as Keytruda®) is approved the FDA to treat multiple cancers, but not approved to treat breast cancer. Fulvestrant (also known as Faslodex®) is approved by the FDA to treat hormone receptor positive metastatic breast cancer. Combining pembrolizumab and fulvestrant is considered investigational. “Investigational” means that the FDA has not approved this combination of drugs for this type of cancer.

BTCRC-BRE16-042 is now open to accrual at the Rutgers Cancer Institute of New Jersey, Michigan State University, and Fred & Pamela Buffett Cancer Center (University of Nebraska).

Funding support for this research study is provided by Merck Sharpe & Dohme Corp.

For more information about this study, including full eligibility requirements, visit www.clinicaltrials.gov (study #NCT03393845).


About the Big Ten Cancer Research Consortium: The Big Ten Cancer Research Consortium was created in 2013 to transform the conduct of cancer research through collaborative, hypothesis-driven, highly translational oncology trials that leverage the scientific and clinical expertise of Big Ten universities. The goal of the Big Ten Cancer Research Consortium is to create a unique team-research culture to drive science rapidly from ideas to new approaches to cancer treatment. Within this innovative environment, today’s research leaders collaborate with and mentor the research leaders of tomorrow with the unified goal of improving the lives of all patients with cancer.

About the Big Ten Conference: The Big Ten Conference is an association of world-class universities whose member institutions share a common mission of research, graduate, professional and undergraduate teaching and public service. Founded in 1896, the Big Ten has sustained a comprehensive set of shared practices and policies that enforce the priority of academics in the lives of students competing in intercollegiate athletics and emphasize the values of integrity, fairness and competitiveness. The broad-based programs of the 14 Big Ten institutions will provide over $200 million in direct financial support to almost 9,500 students for more than 11,000 participation opportunities on 350 teams in 42 different sports. The Big Ten sponsors 28 official conference sports, 14 for men and 14 for women, including the addition of men’s ice hockey and men’s and women’s lacrosse since 2013. For more information, visit www.bigten.org.