CHICAGO, Ill. -- AstraZeneca and MSD, also known as Merck & Co. inside the US and Canada, announced positive data from their phase 3 POLO trial of Lynparza in pancreatic cancer during the ASCO 2019 convention, on Sunday.

The results of the trial are the first positive phase 3 trial of any PARP inhibitor in germline BRCA-mutated (gBRCAm) metastatic pancreatic cancer, a devastating diagnosis with a critical unmet medical need.

Despite the two companies confirming Lynparaza sharply increased progression-free survival (PFS), which was one of its primary endpoints, over the placebo. However, the study showed not much of a significant difference regarding the overall survival (OS) between the two groups.

Korea Biomedical Review exclusively met with Professor Talia Golan, head of Sheba Pancreatic Cancer Center and one of the global investigators for POLO, to see what the results of the trial mean for pancreatic patients and an in-depth explanation into the results of the study.

Question: Can you please explain the importance of the POLO study for pancreatic cancer patients briefly?

Answer: Pancreatic cancer is a very tough disease. What we achieved through the POLO study is that we developed the first biomarker-selected phase 3 clinical study. In the study, we selected a population and gave them platinum-based chemotherapy for a minimum of four months before giving them a maintenance treatment of Lynparza.

In the study, patients were randomized between Lynparza and placebo, and in the patients that received Lynparza, they had a median PFS of 7.4 months versus 3.8 months in the placebo arm.

What’s remarkable is that the median duration of response from the pancreatic cancer patients who responded to the treatment was over two years. Such results are a huge step forward for the patients, and it changes the course of the disease for several patients.

Q: Why is there a four to eight month rest period after the first-line chemotherapy treatment?

A: We have shown as a retrospective data that platinum is an excellent drug for the patients, so we didn’t want to jeopardize them not receiving platinum therapy, but we also didn’t want to over exhaust them with the toxicity profile of the platinum. Although the minimum was four months, the platinum treatments had no limits as long as they responded well to the treatment or were stable. We only moved on to the maintenance therapy if such situations changed.

Q: POLO did manage to increase PFS, but the OS mark showed no significant difference when comparing it to the placebo. Can we call this a win? And if so, why?

A: It’s definitely a win. First of all, the OS data is not yet mature, so we can’t yet maturely interpret that data. The second reason is that a patient who responds to platinum and receives the same treatment again after a resting period ultimately have problems with the toxicity profile of the drug.

We know that platinum is a very good drug for BRCA-related tumors, but the patients cannot go indefinitely with the therapy as the neuropathy accumulates.

The study was designed to develop a maintenance strategy for such patients, and that is why the primary endpoint of the PFS is significant. The research also showed a very ambitious hazard ratio of 0.53, which means that 47 percent of our patients have a PFS interval due to the drug.

I think what the most significant achievement of the trial is that and the POLO trial is the first time a randomized phase 3 study acknowledged the genomic diversity of pancreatic cancer and made it possible for us to focus a specific biological agent, which can be interpreted as precision medicine.

When looking back as other solid tumors we’ve learned in the modern era there is patient, clinical and genomic diversity and we’ve been doing the same thing in breast, lung, and rectal cancer for a decade already.

That is why I think it’s not just about the study results and clinical meaning, but also recognize it as a huge step forward in a disease in which we have not managed to conduct precision medicine on this kind of level.

Q: Is there a reason why pancreatic cancer took longer to achieve such results when compared with the other cancers?

A: Pancreatic cancer is just such a difficult disease to treat. There is no other solid tumor that has such a limited survival. That is why a lot of different clinical trials have been negative in this area.

Q: Do you believe that the good results in the PFS and duration of response will ultimately extend to OS?

A: It’s hard to know. We know patients are also going on to receive additional chemotherapy agents. We can’t know the results, and that’s why we conduct a clinical trial and randomize the clinical trials and not make assumptions and wait for the data. The meaningful parts are that the PFS has statistical value, and in the responding patients, the response goes on for a median of two years.

I have patients that have complete responses, and this is unheard of in treating pancreatic cancer.

So I think it’s significant.

Q: What needs to be confirmed further in this study? Also, what is the research that is being planned in the future?

A: We know that the treatment has activity in other diseases as well and are waiting for some results from combinations with Lynparza in the next year or two. We know that the other genomic alteration in the tumor can have maybe a similar behavior to a g BRCA mutant tumor as well. So those are things that need to be further explored in the clinical and experimental setting.