FDA Approves Pembrolizumab for Pancreatic Cancers with Mismatch Repair Deficiency

Dr. Bert Vogelstein, Pancreatic Cancer Researcher
Bert Vogelstein, M.D. (PRNewsfoto/The Lustgarten Foundation for P)
In an unprecedented, fast-tracked review, the Food and Drug Administration (FDA) approved the use of pembrolizumab (anti-PDI) immunotherapy for patients with advanced pancreatic cancers who have a defect in their capacity to repair DNA.

Support from the Lustgarten Foundation was critical to the success of the clinical trial that demonstrated the efficacy of pembrolizumab to the FDA. In addition to supporting the research, the Foundation has been encouraging and covering the cost for pancreatic cancer patients to receive mismatch repair deficiency (MMR) testing in an effort to increase enrollment in the clinical trial.

Bert Vogelstein, M.D., co-director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center and a Lustgarten Foundation Distinguished Scholar who helped direct this study, said, “It is the first example of ‘personalized immunotherapy.’  A specific immune treatment can now be recommended for patients based exclusively on the genetic characteristics of their tumor.  If the tumor shows a repair defect, then it is very likely that it will respond to this drug, regardless of how advanced the cancer is at the time of treatment.”

It is estimated that approximately 1 in 50 advanced pancreatic cancer patients have MMR in their tumors that make them candidates for this type of therapy. Pembrolizumab (anti-PDI) is the first cancer drug based on a predictive cancer marker, rather than tumor type, to be approved by the FDA.

A study conducted at the Johns Hopkins Bloomberg-Kimmel Institute, funded in part by the Lustgarten Foundation, demonstrated that a small group of patients with advanced cancers had a significant response to pembrolizumab (anti-PD1) immunotherapy. The responsive tumors had a mismatch repair deficiency, resulting in a large number of genetic mutations that stimulate an immune response. However, this native immune response is too weak to reject the tumor. Treatment with pembrolizumab energized this response, resulting in dramatic tumor shrinkages with minimal side effects relative to traditional chemotherapy.

“This is an incredibly important step forward and we are delighted to have had a key role in its success,” said David Tuveson, M.D, Ph.D., Director of Research for the Lustgarten Foundation. “Patients have responded very well to this drug. This is the beginning of personalized medicine for pancreatic cancer patients.”

John Shinnick was diagnosed with pancreatic cancer at age 72 and didn’t think he’d survive the three months of chemotherapy originally recommended to him. After getting a second opinion and a Whipple procedure to remove a portion of his pancreas, John sought treatment at the Johns Hopkins Bloomberg-Kimmel Institute, where he tested positive for MMR and was put in the clinical trial for pembrolizumab in June of 2016. John is still in the trial and doing well.

“Being diagnosed with pancreatic cancer was terrifying.  I am grateful to be receiving the best possible treatment,” John said. “I have a very high quality of life. I don’t feel sick; I feel good.”

The Lustgarten Foundation encourages all patients to get screened for microsatellite instability.  If the test is positive, patients should ask to be treated with pembrolizumab.


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