Keytruda-Chemo Combo Can ‘Reduce Risk of Death’ in Biliary Tract Cancer


Keytruda plus chemotherapy for patients with locally advanced biliary tract cancer helped increase survival for up to two more years, an expert told CURE®.

FDA Approval: What you need to know

Keytruda plus chemotherapy improved survival in patients with biliary tract cancer.

The Food and Drug Administration (FDA) recently approved the drug combination of Keytruda (pembrolizumab) with chemotherapy drugs, gemcitabine and cisplatin, to treat patients with locally advanced, unresectable or metastatic biliary tract cancer.

The Keytruda-chemotherapy combination was approved following results from the phase 3 KEYNOTE-966 trial that included 1,069 patients to determine improvements regarding overall survival, or the period from diagnosis or the start of treatment when a patient stays alive, according to National Cancer Institute.

Biliary tract cancer is a rare type of cancer that forms in cells in the bile duct lining, gallbladder or ampulla of Vater, which is where the liver and pancreas enter the small intestine, as explained by the National Cancer Institute. This type of cancer is known to grow and spread quickly and is typically diagnosed once it has reached an advanced stage, leading to poorer outcomes.

“Most patients, unfortunately, present with advanced disease (and) that means disease that is not possible to do a curative operation. Surgery is possible in only around 15% of patients, which means that for 85% of patients at the time of diagnosis (it) is too advanced for them to receive that surgery,” Dr. Juan Valle, chief medical officer for the Cholangiocarcinoma Foundation and professor of medical oncology at the University of Manchester, said in an interview with CURE®.

“(Keytruda plus chemotherapy) is specifically for patients with advanced disease. And the … KEYNOTE-966 study was able to show that the addition of immunotherapy reduces the chances of patients dying; it can reduce the risk of death. So, for that reason, it’s now emerging as a new treatment for patients with advanced biliary tract cancer,” he said.

Traditional treatment for about a decade in patients with locally advanced, unresectable or metastatic biliary tract cancer was chemotherapy, specifically gemcitabine and cisplatin, Valle noted.

“One of the challenges is that patients aren’t always so fit to receive treatments. So, sometimes people get just one chemotherapy drug, gemcitabine and so on. But this particular indication from the FDA is specifically for patients who are fit enough to receive combination chemotherapy,” Valle said.

With the recent approval of Keytruda plus chemotherapy, researchers found that adding Keytruda to the treatment regimen also improved the rate of survival for patients, Valle noted.

“We know that with chemotherapy, the benefits are modest. By that, I mean that on average, patients will survive 12 to 13 months with chemotherapy,” he said. “And one of the things is that the addition of (Keytruda) showed that one in four patients could reach two years. That’s important because being alive at that time is clearly a benefit to patients. Having said that, you can probably also hear that there’s a long way to go in terms of improving our treatments, increasing that 25% two-year survival (rate) higher as much as we can.”

Although the new drug combination for this patient population has demonstrated improvements, Valle recognized that there are still some unmet needs that need to be addressed in the future.

“With the addition of immunotherapy, we know that some patients really benefit from treatment, maybe that one in four,” said Valle. “So partly, we need to understand who those patients (are) who derive the benefit. Can we determine that front so that we can personalize the treatment and get immunotherapy to those patients and maybe avoid giving side effects and complications to patients who may not benefit?

“Eventually, once patients have received treatment, that cancer will get worse again, and so there will be the emergence of resistance. And what we need to understand is how patients become resistant. Is there something that we can target with that so that we can be wiser about second-line treatment once patients have failed that first line?”

Because immunotherapy as treatment has been around for a while, Valle said, it has a “fairly well-established” side effect profile.

Normal side effects with this drug combination, Valle stated, included diarrhea, skin rashes and reactions to the liver. He also emphasized that blood tests are important for patients to receive in order to monitor areas, such as the thyroid gland and the liver.

Valle also noted although some of the side effects may seem concerning, doctors “are now very familiar with managing the effects of these (Immune checkpoint) inhibitors.”

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