Big News for PARP Inhibitors: They Can Work in Pancreatic Cancer, Too

A study presented at the American Society of Clinical Oncology (ASCO) Annual Meeting today revealed that one of these PARP inhibitor drugs, called olaparib (Lynparza), extended the amount of time that patients with advanced stages of pancreatic cancer who had mutations of the BRCA gene could live without the cancer getting any worse (a measurement doctors call "progression-free survival")

The results were based on a phase III clinical trial called POLO, which enrolled 154 participants total. Everyone in the clinical trial received chemotherapy at first. Then after the chemo, people in one group of the trial were given Lynparza as maintenance therapy (meaning after chemo, to keep the cancer from repairing itself). People in the other group were given a placebo (which is kind of like a drug placeholder, used so that neither group knew whether they were or weren't being given the actual drug).

Ultimately, those in the Lynparza group lived an average of four months longer without their pancreatic cancer getting any worse than the placebo group did. And overall, the addition of Lynparza after chemo decreased the likelihood of the cancer coming back by 47 percent.

One year later, researchers followed up to find that 34 percent of those in the Lynparza group had not shown any signs that their cancer was coming back, compared with 15 percent of those who got the placebo. Then two years later, these numbers were 22 percent and 10 percent, respectively.

The results are encouragingnot only because advanced pancreatic cancer is particularly difficult to treat, but also because this is the first time a PARP inhibitor has been shown to work this way in pancreatic cancer at all.

One caveat worth noting is that the chance of experiencing side effects was much higher for those given Lynzpara (40 percent) than it was for those who were just treated with the chemo followed by a placebo (20 percent). The severity depends on the individual and the cancer, but often, the side effects for PARP inhibitors include anemia, gastrointestinal discomfort like nausea and vomiting, and fatigue.

It's also important to pay attention to the genetic makeup of the pancreatic cancers for those who benefitted from Lynzpara; for the outcomes to improve, it was essential that tumors had BRCA mutations.

"What a BRCA mutation is is a defect in your ability to repair a double strand break," Dr. Rebecca Arend, assistant professor in gynecologic oncology at the University of Birmingham in Alabama, previously explained to SurvivorNet. "If you have a PARP inhibitor [like Lynparza], then you can’t repair that single strand break."

Dr. Arend explained this phenomenon to us in the context of ovarian cancer treatment, but it works the same way in pancreatic cancer, according to the news presented today.

So to summarize, the chemo drugs kill the cancer cells by damaging their DNA. Then afterward, when they would normally start repairing their DNA, the PARP inhibitor drug swoops in and, with the help of the specific BRCA defect, halts the repair process.

Because having a BRCA mutation may mean you're eligible for this new type of treatment, it's important to talk to your oncologist about getting genetic testing done as soon as your initial diagnosis.

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