Experimental drug doubles 1-year survival rate for pancreatic cancer

An experimental treatment doubles the one-year survival rate for pancreatic cancer, one of the deadliest cancers, a new study reports.

The drug, called elaglusib, targets the protective mesh that pancreatic tumors build around themselves, helping immune molecules and chemotherapy penetrate the tumor. Results from a trial demonstrating the safety and efficacy of elaglusib were published April 14 in the journal Nature Medicine.

“For the first time, we are beginning to see effective drugs outside of the standard chemotherapy that has been used for pancreatic cancer for the past 20 years,” said study co-author Dr. Devalingam Mahalingam, an oncologist at Northwestern University Feinberg School of Medicine.

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A rare victory in pancreatic cancer treatment

Pancreatic cancer has one of the poorest prognoses of all cancers, with newly diagnosed patients having only a 13% chance of surviving five years with the disease. The problem is that pancreatic cancer is often not detected until it is quite advanced.

“Unfortunately, most patients have advanced disease,” Mahalingam told Live Science. “There are no screening tools to detect problems early.”

In addition, the area around the tumor, called the tumor microenvironment, poses problems in the treatment of pancreatic cancer. “They are very dense and fibrous, which reduces the effectiveness of common treatments such as chemotherapy,” he said.

Elraglusib addresses this problem by inhibiting a protein called glycogen synthase kinase 3 beta (GSK-3 beta).

Petri dish studies have previously shown that GSK-3beta helps pancreatic cancer cells survive by increasing the activity of a protein called nuclear factor κB, which helps pancreatic cells resist programmed cell death (essentially the cell’s “self-destruct” button). The drug also inhibits molecules that make tumors resistant to the immune system.

Elraglusib increases survival time

Previous studies have shown elaglusib to be safe for patients with a variety of cancers, but to see if it improves outcomes in pancreatic cancer, Mahalingam and colleagues tested the drug in 286 people who had recently been diagnosed with pancreatic cancer. Patients received chemotherapy with or without elaglusib. Almost all patients in the trial had advanced metastatic disease. This means the cancer had spread beyond the pancreas to other parts of the body.

Half of the patients who received elaglusib and chemotherapy were still alive after 10.1 months, and half of the patients who received chemotherapy alone were alive after 7.2 months. Among patients given elaglusib, 42% survived one year after diagnosis, compared with 22% of patients who received chemotherapy alone.

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Although elaglusib increased overall survival, it did not extend how long patients could live without their cancer growing or spreading to new areas.

The trial’s protocol calls for patients to stop treatment if their disease progresses, and Mahalingam said the trial’s subjects are critically ill, meaning there is a high chance of progression. As a result, some patients were switched to palliative care before the effects of the drugs became clear. Mahalingam speculated that these patients might have lived longer if the trial had continued and given higher doses of the drug.

Future treatment options

In lab dish and animal studies, elaglusib made the environment around tumors more permeable to immune cells and chemotherapy, reducing the ability of tumor cells to fight off immune cells that had infiltrated the tumor.

These abilities, combined with the drug’s safety, could make it a useful complement to other pancreatic cancer treatments, such as immune checkpoint inhibitors, which enhance the immune system’s ability to recognize and kill tumor cells, and KRAS inhibitors, which block mutated proteins that promote tumor growth, Mahalingam said.

Elraglusib could potentially be used in combination with chemotherapy to treat other types of cancer, Mahalingam noted. A decade ago, other GSK-3 beta-targeting drugs were tested in other solid tumor cancers, but they never made it past the early stages of clinical trials. However, while therapeutic doses of these drugs did not reach the tumor, elaglusib overcame that obstacle, Mahalingam said.

This new study is also notable because the drug was developed without the involvement of major pharmaceutical companies.

“Developing a drug from an academic institution is never easy,” he added. “It’s nice to see some things come to fruition.”