Pancreatic Cancer Awareness Month Brings Attention to Growing Incidence and Treatment Advances

During Pancreatic Cancer Awareness Month, which occurs in November each year, Suneel Kamath, MD, took to the OncLive^® X account (formerly Twitter) to shed light on importance of recognizing this disease and share factors that place patients at a higher risk for diagnosis.

Pancreatic cancer remains one of the deadliest cancers in the United States, and its incidence of has been rising annually, Kamath explained in a post. Per the American Cancer Society, 66,440 new diagnoses and 51,750 deaths due to pancreatic cancer are projected for 2024.

“Pancreatic cancer awareness is so important. It's a disease that we've made some progress in over the last 20 to 25 years, but it certainly remains a very deadly disease that we need [to devote] a lot more attention to,” he stated in an interview with OncLive regarding the X Takeover.

In the interview, Kamath, an assistant professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in Ohio, discussed key takeaways from several of his posts, including the rising incidence of this disease in younger adults and ongoing research into new treatment approaches within the pancreatic cancer space.

OncLive: Why is it important to recognize Pancreatic Cancer Awareness Month?

Kamath: Awareness and attention are how we get funding and support for research [in pancreatic cancer]. I've seen with several of the advocacy groups—like the Pancreatic Cancer Action Network—great advocacy and fundraising initiatives. They've turned a lot more attention to this disease and as a result of that, we've had more new treatments and more research into the pathways that [drive] it. That's how we're going to make our way forward to make the treatments for this disease better.

What are some of the key factors contributing to the rising incidence of pancreatic cancer, and how have advances in genetic testing and screening strategies improved early detection and screening of high-risk individuals?

It's alarming how much [pancreatic cancer] has become more and more common over the last 20 to 25 years. I remember when we would look at SEER statistics for this disease from the mid and late 2000s, [new cases] would be [approximately] in the 40000s and low 50000s, and we're [projected to be] up to almost 67000 cases in 2024. At this point, we don't know why that is, and that's part of the difficulty with pancreatic cancer.

Unlike many other tumor types, there aren't a lot of modifiable risk factors for [pancreatic cancer]. It's not strongly associated with smoking; it is maybe a little bit [correlated] with alcohol [consumption]. We know that obesity is a risk factor, but not strongly so. However, at a population level, approximately 70% of the United States is either overweight or obese; therefore, if you have hundreds of millions of people in that situation, you are going to see more cases of this type of cancer. I do think that's part of it, but there's probably some other factors that we haven't identified yet.

[Pancreatic cancer] is a difficult disease as far as screening and detection is concerned, too. There's no predefined screening for an average-risk patient. Unlike with breast or colon cancer, where we have great guidelines and great ways to screen, there are no well-studied, recommended screening strategies.

[Now], we're doing a better job of identifying people who are high risk through genetic testing and in terms of [identifying] precursor lesions that can be tracked called intraductal papillary mucinous neoplasms [IPMNs]. They're often run by gastroenterologists who do an amazing job of monitoring people with imaging every 6 to 12 months. You can catch someone that's converting from benign IPMNs to pancreatic cancer, and in doing so, you can catch those much earlier in a state where we can still [potentially] cure it. As we screen more people in terms of germline genetic testing, the more people we identify that are high risk. We can screen those people and catch [their disease] earlier, or maybe even prevent [the disease] from occurring in the first place.

In the takeover, you also mentioned KRAS mutations, which you referred to as the “once undruggable mutation.” How have treatment strategies targeting these alterations evolved?

We are so excited for KRAS inhibition in gastrointestinal [GI] oncology, especially for pancreatic cancer. These mutations are present in approximately 90% of all [pancreatic cancers]. We have [other targets, such as] NRG1 fusions, microsatellite instability–high [disease], and BRAF alterations, all of which [have a much lower] incidence [in pancreatic cancer]. Even if a drug is extremely effective against [these targets], it's hard to get that excited about it vs a target that is present in 9 out of 10 cases. The possibilities of having an effective therapies for [different KRAS alterations] and how many people we could affect [is exciting].

For right now, [KRAS inhibition] hasn't really changed the standard of care much. I would say [we are] still largely using chemotherapy [with regimens such as] FOLFIRINOX [leucovorin, fluorouracil, irinotecan, and oxaliplatin] and gemcitabine plus nab-paclitaxel [Abraxane]. There are a lot of clinical trials out there and different ways of attacking KRAS alterations, whether it's pan-KRAS or specific targeted agents. KRAS G12D is the most important [target] in this disease, and there are a few things out there that I'm excited by.

What ongoing trials targeting KRAS mutations in pancreatic cancer are you most excited about or closely following?

There are 2 trials that we're going to be participating in at the Cleveland Clinic. One of them is [using the] KRAS G12C inhibitor [olomorasib] developed by Lilly, and the other one is a Pfizer study [evaluating] the pan-KRAS inhibitor [PF-07934040], so we are looking at it a couple different ways. The jury is still out in terms of whether you want something that's a global RAS inhibitor, or if it is better to have a drug targeted toward a specific mutation.

At least early on, it seems like the [selective agents] are helpful. There were [broader] SHIP2 and SOS1 inhibitors [in development], but those haven't quite panned out as much as we had hoped.

I am excited about [olomorasib and PF-07934040] because they're oral drugs with reasonably good safety profiles. These [agents] are still in phase 1 [testing], so there's a lot to learn. A lot of this excitement [is about their] potential, rather than where [the treatment arsenal is] at today. [Overall], the potential impact of [KRAS inhibition] is huge for so many people who need it.

Reference

Key statistics for pancreatic cancer. American Cancer Society. February 5, 2024. Accessed November 26, 2024. https://www.cancer.org/cancer/types/pancreatic-cancer/about/key-statistics.html