Alex Trebek's Pancreatic Cancer Diagnoses Focuses Attention on the Tough-to-Treat Disease

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Alex Trebek, 78, host of TV game show “Jeopardy” announced yesterday that he had been diagnosed with stage 4 pancreatic cancer. In the video posted to the show’s YouTube channel, Trebek said, “Now, normally, the prognosis for this is not very encouraging, but I’m going to fight this. And I’m going to keep working and with the love and support of my family and friends—and with the help of your prayers also—I plan to beat the low survival rate statistics for this disease.”

In late August 2018, famed singer Aretha Franklin died from a neuroendocrine tumor of the pancreas, which brought attention to the disease as well. Apple founder Steve Jobs also died from neuroendocrine tumors of the pancreas, which are the rare type of pancreatic cancer.

Like cancer in general, pancreatic cancer is not a single disease. According to the National Cancer Institute (NCI), about 55,440 cases of pancreatic cancer are diagnosed annually, representing about 3.2 percent of new cancer cases. Annually, 44,330 Americans die from the disease, which is about 7.3 percent off new cancer deaths. It is currently the third-leading cause of cancer death in the U.S. But it’s also a deadly cancer, with only 8.5 percent surviving for five years.

But the specific type of cancer diagnosed, which Trebek has not specified, makes a significant difference in prognosis. Anirban Maitra, scientific director of the Sheikh Ahmed Pancreatic Cancer Research Center at the University of Texas MD Anderson Cancer Center, told Forbes in August, “The first thing to do if somebody gets a diagnosis of pancreatic cancer is to know what they are dealing with. Because everything they deal with will change dramatically based on that.”

A Novartis drug, Afinitor, has been shown to help patients whose neuroendocrine tumors have spread outside the pancreas. The more common type of pancreatic cancer is adenocarcinoma, which has an even worse prognosis. This is the type of pancreatic cancer that caused the deaths of Dirty Dancing actor Patrick Swayze and opera singer Luciano Pavarotti.

For these types of cancers, there are typically two chemotherapy regimens, one a combination of Gemzar and Abraxane, and the other a mixture of drugs called FOLFIRINOX. In the average patient they extend survival from about four months to nine months.

Surgical removal of the tumor when it’s small gives the best odds of survival. The problem is that pancreatic cancer is typically diagnosed rather late based on symptoms that include abdominal pain, jaundice, and weight loss. By that time, the cancer has often spread and surgery is not an option. Diagnosis is performed using a CT scan or an invasive procedure like a needle biopsy and invasive ultrasound.

Nicole Fawcett, writing for the University of Michigan Health Lab Blog, says, “It grows in an unusual pattern in which tentacles extend into the nerves and blood vessels. This creates challenges for surgeons and radiation oncologists who must work around these critical structures. It’s one reason only 20 percent of patients can have surgery.”

There are currently about 1,000 ongoing clinical trials for pancreatic cancer. Some pancreatic cancer news of note include:

In February, AstraZeneca and its research partner Merck & Co. announced positive data from their Phase III POLO trial of Lynparza in pancreatic cancer. The companies said that the trial showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) as first-line maintenance therapy alone in patients with germline BRCA-mutated (gBRCAm) metastatic adenocarcinoma of the pancreas in patients who haven’t responded to platinum-based chemotherapy. The trial compared Lynparza (olaparib) to placebo.

Also in February, Researchers at Zhenjiang University in China published research in the Journal of Oral Microbiology describing how differences in bacteria living on the tongue may be able to diagnose early-stage pancreatic cancer. 

“If an association between the discriminatory bacteria and pancreatic cancer is confirmed in larger studies, this could potentially lead to the development of new microbiome-based early diagnostic or preventive tools for the disease,” stated lead author Lanjuan Li.

In September 2018, the FDA granted FibroGen Fast Track designation for pamrevlumab, an anti-CTGF antibody for the treatment of idiopathic pulmonary fibrosis (IPF). The company also expects Phase III trials in IPF and pancreatic cancer to start in 2019.

One biotech startup, Nivien Therapeutics, which spun out of Harvard University research, is working on an approach to treating the disease based on a biochemical system called Hippo. Hippo controls a group of proteins, including CDA and ABCG2, that are involved in cancer metabolism and removal of chemotherapy agents inside the cell.

Another biotech company, which came out of stealth mode in June 2017, is Vivace Therapeutics, which is also working on the Hippo-YAP signaling pathways. It is working on novel therapeutic antibodies called BINSpecific antibodies, that bind in an almost irreversible and cell-type specific manner to target cells.

And Halozyme Therapeutics is working on developing PEGPH20, which breaks through the stroma to allow chemotherapy into the tumor. The technology the company uses is ENHANZE drug-delivery, based on a patented recombinant human hyaluronidase enzyme (rHuPH20). The gist of the technology is that it allows cancer drugs better access to cancers that tend to have structures that prevent chemical access.