Metastasis-Directed Therapy Shows Benefits in Some Pancreatic Cancer

Adding metastasis-directed therapy to chemotherapy showed some benefit in patients with oligometastatic pancreatic cancer, according to data from a phase 2 study.

In the phase 2 study, published in the Journal of Clinical Oncology, metastasis-directed therapy describes local therapy that was added to chemotherapy. This form of metastasis-directed therapy included high-dose radiation therapy or external beam radiation, to target approximately 95% of lesions, said lead study author Dr. Ethan Ludmir.

Ludmir is an assistant professor in the Department of Gastrointestinal Radiation Oncology at The University of Texas MD Anderson Cancer Center in Houston.

He also explained in an interview with CURE® that oligometastatic cancer is when there are only a few sites where the cancer has metastasized (spread), compared with metastatic cancer, which may have many sites of metastases.

“It is possible that by adding local therapy — metastasis-directed therapy — with radiation or another technique, [doctors] could improve outcomes for these patients [with oligometastatic pancreatic cancer],” Ludmir explained. “So, this has really been the subject of not only this trial, but many others that have been done and are being done to really move the needle for patients with metastatic cancer.”

Metastasis-Directed Therapy in Oligometastatic Pancreatic Cancer

In the study, Ludmir and fellow researchers included 40 patients, who were randomly assigned to receive either metastasis-directed therapy with chemotherapy (19 patients) or chemotherapy alone (21 patients). All 40 patients were evaluated for progression-free survival (PFS; patients living without signs of their disease worsening or spreading).

At a median follow-up of 17 months, the median PFS time was 10.3 months in the metastasis-directed therapy group and 2.5 months in the chemotherapy alone group, the study noted. The researchers found that adding metastasis-directed therapy to chemotherapy significantly improved PFS.

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Based on these results, Ludmir noted that radiation plus chemotherapy helps the immune system realize cancer is present, especially because cancer typically hides well from the immune system.

“I think one of the most interesting findings is that we had patients give blood samples as they went through the treatment course. When we worked with our basic scientist colleagues, we wanted to know whether there were changes in the immune system as a result of either getting the radiation or not getting the radiation,” Ludmir said. “What was really interesting is that the patients who got radiation had an impressive activation of their systemic immune profile, which is to say they had increased levels of inflammatory cytokines, circulating activated T cells and an overall portfolio that suggested that the immune system might be revved up and potentially educated as to potentially how to target cancer cells elsewhere in the body.”

Ludmir explained that using high-dose radiation would be “effectively blowing up cancer cells.”

“[This exposes] the immune system to those cancer neoantigens — those cancer proteins —that the cancer was otherwise doing a pretty good job of hiding from the immune system,” Ludmir said. “We know that pancreas cancer has been a pretty tough nut to crack in terms of getting it to respond to immunotherapy. This now raises the possibility that by doing radiation, we're kind of taking two shots on goal. We're both treating the cancer we can see and letting the immune system now have a chance to really identify and control the cancer we cannot see: the microscopic disease.

“So the future is very bright as we think about potential roles for radiation to augment immune surveillance for pancreas cancer.”

The Future of Metastasis-Directed Therapy for Oligometastatic Pancreatic Cancer

As of now, metastasis-directed therapy still has to be studied more, Ludmir emphasized.

“Unfortunately, moving the needle has been exceedingly hard [for pancreatic cancer],” he said. “In the last 15 years or so, we've seen some incremental improvements in systemic therapy, but realistically, metastatic pancreas cancer remains an exceedingly challenging disease to treat.”

Soon, Ludmir said, a phase 3 portion of the trial will open to help identify whether this therapy will one day become a treatment option for patients with oligometastatic pancreatic cancer.

“Typically, this metastasis-directed therapy of radiation is fairly brief,” he explained. “Typically, the radiation courses that we’ve given folks are between one and two weeks long, and the goal is to deliver, using fairly sophisticated radiation techniques like stereotactic body radiation, to deliver high-dose radiation over a short amount of time, which carries several benefits.

“Number one, the radiation is typically very well tolerated by patients, and that was born out in this clinical trial data report that we have here in the Journal of Clinical Oncology. Secondly, it also minimizes patients being taken off of chemotherapy and minimizes downtime. Pancreas cancer is the sort of thing where you really don't want to give it a break too much off of chemo, because we know once the cancer is metastatic, we don't want to give it the chance to grow during any interval of systemic therapy.”

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