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Alex Trebek, Harry Reid and Their Pancreatic Cancer Treatment

— Exploring a 'triangle offense' against the disease

MedpageToday
Photos of Alex Trebek and Harry Reid

Just two days before his 80th birthday, "Jeopardy!" host Alex Trebek (GMA) to announce the publication of his book The Answer Is...: Reflections on My Life, and to give fans an update on his pancreatic cancer battle.

Trebek had been diagnosed with stage 4 pancreatic cancer in February 2019 and made the diagnosis public the next month. He seemed to be responding to his chemotherapy regimen, and by June he told GMA's Robin Roberts that he was in "near remission." But the treatment was not without a toll, as he admitted that the chemotherapy had left him tired and occasionally depressed. After another round of chemotherapy, he was cleared to switch to immunotherapy.

By September 2019, things were not going as well -- he had lost 12 pounds, and his "numbers went sky high." Doctors put him back on chemotherapy. In his most recent GMA interview, Trebek was candid about the difficult moments he has had over the past several months, dealing with fatigue, depression, and pain that keeps him up at night. But he says it's his love for his show that keeps him going: "It's something that I can't explain intellectually. At a gut level, without even thinking about it, it just happens. I suddenly wake up and I'm able to perform and handle the show because I like it."

Currently, Trebek is undergoing an experimental immunotherapy treatment also used by former U.S. Sen. Harry Reid (D-Nev.).

Reid was diagnosed with pancreatic cancer in May 2018. He underwent surgery at Johns Hopkins University, followed by chemotherapy and radiation treatments. However, his cancer worsened. Fearing he was near death, he got in touch with , inventor of the protein-bound paclitaxel suspension sold as Abraxane. Soon-Shiong was working on a combination treatment that he refers to as a "triangle offense" for refractory metastatic cancers such as breast, lung, and pancreas. Reid became one of four patients in his compassionate use program. Reid travelled from his home near Las Vegas to Soon-Shiong's office in Los Angeles. After six months of treatment, no evidence of cancer was found on Reid's scans. A confirms that Reid is still in remission, nearly two years after his diagnosis.

Trebek also seems to be on the regimen. "They do a blood test to see what my CA-19 numbers are," Trebek explained. "And the CA-19 numbers are an indicator of how your pancreatic cancer is progressing. Eight weeks ago, the numbers were at about 3,500. Now, they're below 100. So I'm going in the right direction. The doctors have said they have never seen a chart like mine because there are peaks. I said, 'What do you mean -- you don't -- you haven't -- you don't see that often? What do you usually see?' They usually see it going up. I'm a bit of an anomaly."

CA-19 (cancer antigen 19-9) is frequently used to monitor pancreatic cancer and cancer treatment.

Although Trebek doesn't want to get ahead of himself, he is feeling a bit more optimistic. "So there's something in the back of my mind that says, 'Woah, hold on a second, host, breathe. Maybe you're gonna be around for a little while longer,'" Trebek added. "And that would be so nice."

What is the 'Triangle Offense'?

Conceptually, Soon-Shiong's "triangle offense" is a combination therapy consisting of multiple drugs with different mechanisms of action, with an emphasis on harnessing and stimulating the immune system to kill cancer cells.

One component of the combination therapy is the experimental biologic N-803 (previously known as ALT-803). N-803 is a laboratory manufactured fusion protein that mimics the effect of interleukin 15 (IL-15). IL-15 is a naturally occurring cytokine that induces the proliferation and action of the immune cells that attack cancer, such as natural killer (NK) cells and cytotoxic T-cells.

Another component of the therapy is haNK CD-16 NK cells. These cells are derived from a cell line originally isolated from a patient with non-Hodgkin lymphoma and subsequently engineered to express IL‐2 and the high affinity CD16 allele. Studies that NK cells, when combined with an immune checkpoint inhibitor such as the anti-PD-L1 antibody avelumab (Bavencio), can mediate antibody-dependent cell-mediated cytotoxicity of tumor cells.

For more details on this approach, please see the . As of July 27, 2020, this study is currently recruiting new patients.

Michele R. Berman, MD, and Mark S. Boguski, MD, PhD, are a wife and husband team of physicians who have trained and taught at some of the top medical schools in the country, including Harvard, Johns Hopkins, and Washington University in St. Louis. Their mission is both a journalistic and educational one: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.