Expert Highlights Progress and Next Steps in Early Pancreatic Cancer

Allyson Ocean, MD

Recent strides have been made in the treatment of patients with early or locally advanced pancreatic cancer, according to Allyson Ocean, MD, with the emergence of several novel strategies resulting in significant survival gains for patients.

For example, the pivotal phase III PRODIGE 24/CCTG PA.6 trial showed that adjuvant treatment with modified FOLFIRINOX led to significantly longer survival compared with gemcitabine in patients with resected pancreatic cancer, with a median overall survival (OS) of 54.4 months and 35.0 months, respectively, leading to a 36% reduction in the risk of death (HR, 0.64; 95% CI, 0.48-0.86; P = .003).1 Based on these data, modified FOLFIRINOX became the new standard of care in this setting.

“This definitely was a game changer for patients with pancreatic cancer,” said Ocean. “We now have a treatment regimen that has been shown to extend life significantly. For patients who are able to receive FOLFIRINOX in the adjuvant setting, it should be given because of that significant survival advantage.”

In the neoadjuvant setting, data from the phase III PREOPANC-1 trial suggest that preoperative chemotherapy in combination with radiation can lead to improved survival rates in patients with resectable or borderline resectable pancreatic cancer over that of immediate surgery.2 In the intent-to-treat population, the use of chemoradiotherapy resulted in a median OS of 17.1 months versus 13.7 months with immediate surgery followed by adjuvant chemotherapy (HR, 0.74; P = .074). However, the results are preliminary.

Despite this progress, challenges remain with detecting the disease before it’s determined unresectable or metastatic, said Ocean. Several research efforts are ongoing to address this issue, including emerging blood-based assays and screening tests, she added.

In an interview during the 2019 OncLive^® State of the Science Summit™ on Gastrointestinal Cancers, Ocean, an associate professor of clinical medicine at Weill Cornell Medicine, discussed pivotal trials in early pancreatic cancer, the need for genetic testing, and other research efforts focused on improving patient outcomes.

OncLive: What are some key updates in early or locally advanced pancreatic cancer treatment?

Ocean: Some recent advances [in the neoadjuvant space] include a large clinical trial, which showed the benefit of a certain chemotherapy regimen in the adjuvant setting, as well as another clinical trial, which showed a potential benefit for pretreatment in potentially resectable cancers.

Could you expand on the PRODIGE 24/CCTG PA.6 trial and the significance of its findings?

PRODIGE 24/CCTG PA.6 was a pivotal phase III trial that looked at the comparison of two chemotherapy regimens, FOLFIRINOX and gemcitabine, in the adjuvant treatment of patients with pancreatic cancer. Before this trial, the standard of care was gemcitabine alone or gemcitabine with capecitabine, and this trial showed very positive results in favor of FOLFIRINOX for adjuvant therapy. The median OS in this trial was approaching longer than 4 years, which is incredible for this disease.

What are the key remaining challenges in the pancreatic cancer space?

Pancreatic cancer is a very difficult cancer to treat. Most of the time, this disease is detected very late and it is already metastatic. We need to get more patients enrolled on clinical trials. Very few patients with this disease enter clinical trials, and the only way that we're going to improve outcomes is if we do more research through clinical trials. Another challenge has to do with early detection of the disease. A lot of research and emphasis is being put into efforts dedicated to earlier detection, such as potential blood tests or screening tests. [We want] to find the disease before it becomes a major problem—before it's unresectable or metastatic.

What do some of these efforts look like?

Some advancements have been made in earlier detection of pancreatic cancer. For example, we now know that about 1% of new-onset diabetics have a risk factor of developing pancreatic cancer. Therefore, we are starting to look into that patient population and those who are newly diagnosed with diabetes later in life. Additionally, a blood test designed to look for pancreatic cancer at its earliest stage is currently under development in trials.

There is also a recent guideline-changing recommendation that all patients diagnosed with pancreatic cancer should have genetic testing done. This is because we may be able to find an actionable mutation in their germline or in their tumor and could lead to different treatments. We also want to know if patients potentially have a mutation that predisposes them to pancreatic cancer, because we want their family members to be tested as well. [To this end], an ongoing study called GENERATE allows patients' family members to receive free genetic testing if their family member, a parent or first-degree relative, has pancreatic cancer with a known genetic mutation.

How is circulating tumor DNA (ctDNA) being used in this space?

The issue with ctDNA analysis in pancreatic cancer is that it's not yet mainstream. People are doing it—I have done it occasionally for patients—but it's still in its infancy in terms of directing therapy. Some problems with it exist. [For example], sometimes we get results that have confounding factors, where it's not necessarily all tumor DNA. Trials and experimental protocols are looking into the use of ctDNA to predict disease recurrence, as well as to sequence that DNA to come up with better therapies; those efforts are all ongoing. It's still some time away for [this approach] to become mainstream and used by everyone in the treatment of patients with pancreatic cancer.

What is the key takeaway that your colleagues should know about the treatment of patients with early or locally advanced pancreatic cancer?

Patients with pancreatic cancer who are able to have surgery and receive FOLFIRINOX will experience a significant survival advantage. I also want people to realize that there are also data for neoadjuvant treatment of patients with pancreatic cancer, including the combination of chemotherapy and radiation prior to surgery.

Those studies all point to the fact that patients can benefit more if they have treatment prior to surgery followed by adjuvant therapy. I also want to remind everyone that genetic testing is mandatory for patients with pancreatic cancer, and they should do their best to enroll patients on clinical trials.

References

1. Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379(25):2395-2406. doi: 10.1056/NEJMoa1809775.
2. Tienhoven GV, Versteijne E, Suker M, et al. Preoperative chemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): a randomized, controlled, multicenter phase III trial. J Clin Oncol. 2018;36(18 suppl; abstr LBA4002). doi: 10.1200/JCO.2018.36.18_suppl.LBA4002.