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Bekaii-Saab Highlights Emerging Agents in Pancreatic Cancer Pipeline

Danielle Bucco
Published: Friday, Mar 30, 2018

Tanios Bekaii-Saab, MD
Tanios Bekaii-Saab, MD
The increasing incidence of pancreatic cancer could make the malignancy the second-leading cause of cancer-related death in the United States, making it imperative to find new treatment options, explains Tanios Bekaii-Saab, MD.

PARP inhibitors are one of the treatment strategies being developed for patients with BRCA1/2-mutated pancreatic cancer, as those mutations are known to be sensitive to PARP inhibition across several cancer types. Three PARP inhibitors currently being investigated include veliparib (ABT-888), olaparib (Lynparza), and rucaparib (Rubraca), particularly in the maintenance setting.

Other approaches are also being explored, noted Saab, pointing to ongoing studies of PEGPH20 and stemness inhibitors.

In an interview during the 2018 OncLive® State of the Science Summit™ on Gastrointestinal Cancers, Bekaii-Saab, a professor of medicine at Mayo Clinic, discussed emerging treatments offering hope to patients with pancreatic cancer.

OncLive: Please discuss the current state of pancreatic cancer treatment.

Bekaii-Saab: Pancreatic cancer is leading the trend in terms of increasing incidence. The mortality of pancreatic cancer continues to be on the rise. In fact, if nothing is done to change this, it will be the second cancer killer in the United States, creating an urgency to find new treatments. 

Over the last few years, we have developed new strategies to extend survival for our patients. Half of the patients are crossing the 1-year survival line, with 25% crossing the 2-year survival line. We have patients who survive 3, 4, and 5 years, but it is less than 5% of patients. However, this would be unheard of 5 or 6 years ago, so we are doing better. We are on the right path to ultimately bring pancreatic cancer into the mainstream.

The key in treating pancreatic cancer is to make sure that we have a strategy. The nihilism that surrounds this cancer and its high mortality has left many physicians to overlook sequencing. The thought was to find the best treatment first and figure out the rest later. Like other cancers, we need to start thinking about sequencing. 

There are 2 main pathways for this cancer. My preferred sequence is to start with gemcitabine and nab-paclitaxel (Abraxane), typically biweekly, as it preserves the outcome and seems to significantly improve the toxicity profile. Patients are less likely to tolerate this with a different dose. When patients fail gemcitabine and nab-paclitaxel, then they can receive 5-fluorouracil (5-FU) and MM-398 (irinotecan liposome injection; Onivyde) based on the NAPOLI-1 trial. Then in the third-line setting, we move to a platinum-based regimen such as FOLFOX (5-FU, leucovorin, and oxaliplatin) or cisplatin. 

The reason why FOLFOX has been pushed further down the line is because there were 2 conflicting studies; 1 was from Canada and 1 was from Europe. One showed some benefit, whereas the other showed detriment. I do not buy the detriment study, but it shows that there is no benefit.

We published a meta-analysis that showed all of the experience with phase III studies of oxaliplatin and irinotecan. What was found was that the irinotecan class of compounds tends to improve outcomes with progression-free survival (PFS) and overall survival (OS). The oxaliplatin-based regimens improved PFS, but did not improve OS. They are less likely to benefit patients. 

Overall, the sequence in that group is gemcitabine and nab-paclitaxel, 5-FU, and if patients get to the third-line, oxaliplatin. However, if there is a clinical trial, that takes precedence. 

The other way to treat patients is to start with FOLFIRINOX (5-FU, leucovorin, irinotecan, and oxaliplatin). That is an aggressive regimen. Even for the younger and more performant patients, I argue that you should always consider 1 strategy or the other because we do not have any trial that has compared the 2.

Also, the toxicities can be quite tough and cumbersome on patients. However, if you choose to go down that path with FOLFIRNOX in the first-line setting, the second-line setting is more obscure because there are not a lot of data. We need to take inference from smaller studies. Gemcitabine and nab-paclitaxel could be an option for some patients if they do not have the stamina, but gemcitabine as a single agent does not have much activity.

In the third-line space, there are not many options left. That is assuming the patients have a performance status of 1. If the patient has a performance status of 2 and above, those patients do not seem to benefit from any therapy and seem to be candidates for best supportive care and hospice.




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