Pancreatic cancer: 4-drug chemo regimen may improve survival rates

• Pancreatic cancer is notoriously difficult to detect early enough to treat effectively. This means limited treatment options for many people at the point of diagnosis.
• There have been few advances in developing treatments for pancreatic cancer, but results from a trial reported at a conference have shown an overall increase in survival time.
• The trial looked at the effect of four chemotherapy drugs given in combination to pancreatic cancer patients whose cancer had spread, compared to a two-drug regimen.

Up to four out of five people with pancreatic cancer are diagnosed in the later stages of the disease, contributing to its low 5-year survival rate compared to many other cancers.

The overall 5-year survival rate for pancreatic cancer is 5-10%, and of those diagnosed when cancer has already spread, stage four, the 5-year survival rate is just 1%. While improvements have been seen in survival rates for many other types of cancer, the lack of treatment options for pancreatic cancer patients means this type of cancer is predicted to become the second most frequent cause of cancer-related death by 2030.

Dr. Anton Bilchik, surgical oncologist and chief of medicine and Director of the Gastrointestinal and Hepatobiliary Program at Providence Saint John’s Cancer Institute in Santa Monica, CA, told Medical News Today in an email:

“Pancreas cancer is one of the most chemotherapy-resistant tumors. One of the reasons is that it is typically surrounded by a thickened scar (fibrosis) which makes chemotherapy penetration difficult. Another reason is that the majority of patients with pancreas cancer present with advanced disease at a point where it has already spread.”

Few drugs are available to treat pancreatic cancer, with treatment options based on drugs designed for other types of cancer, said Prof. Andrew Biankin, Regius Chair of Surgery and Director of Translational Research Centre at the University of Glasgow, during an interview with MNT.

Prof. Biankin pointed to four genetic mutations that tended to occur in pancreatic cancer, making it particularly difficult to treat.

“Pancreatic cancer is a particular nasty combination of [mutations in] four genes, which is KRAS, p53, p16, and SMAD4; they are the most common ones. And then after that, it’s very diverse. But something about that combination, those four mutations makes it particularly nasty.”

First beneficial outcome in a decade

For the first time in about a decade, a drug trial has demonstrated a positive effect on survival for patients with stage four pancreatic cancer. The results were reported at the ASCO GI Cancers Symposium on January 20, 2022.

The trial, led by researchers at UCLA Jonsson Comprehensive Cancer Center, included 770 patients in more than 25 countries who had pancreatic cancer that had spread and had not received any previous treatment.

Previous trials testing a two-drug combination had shown an improvement in pancreatic cancer survival, over a single drug, and the team had wanted to see if four was better than two. Dr. Zev Wainberg, lead author who presented at the conference, co-director of the UCLA Health GI Oncology Program, and researcher at UCLA Jonsson Comprehensive Cancer Center told MNT in an email:

“A variant called FOLFIRINOX has been tested by the French about 10 years ago, it offered improvement over a 1 drug regimen (gemcitabine). However, no head to head studies [has] ever been done comparing that multi-agent chemo to a two drug combo (gemcitabine + Nab-paclitaxel). We wanted to ask whether in a head to head manner, [were] four drugs better than two?”

Researchers separated the participants into two arms of the study, with one set given a four-drug regimen of chemotherapies including liposomal irinotecan, 5-fluorouracil/leucovorin, and oxaliplatin – together referred to as NALIRIFOX. The two-drug therapy consisted of nab-paclitaxel and gemcitabine.

Participants in the four-drug group had an overall survival of 11.1 months, compared with 9.2 months for those in the two-drug arm. Progression-free survival was 7.4 months versus 5.6 months with the two-drug therapy.

However, side effects were more common in participants with the four-drug regime.

New approach to treating pancreatic cancer

Prof. Biankin, who was not involved in the trial, said research into pancreatic cancer cures was important, and more needed to be done. He is the lead for the Precision-Panc trial, which is taking place across 30 centers in the United Kingdom and helps allocate pancreatic cancer patients to specific trials based on the mutations their cancer displays. This more personalized approach means that pancreatic cancer patients are given drugs meant to target their specific type of cancer.

Previously it was rare to get a biopsy of pancreatic cancer, but now that more is understood about the pancreatic cancer genome, this trial has been ensuring this happens. He said: “So what we’ve found since we sequenced the pancreatic cancer genome in 2012 is that we see the targets in the pancreatic cancer, the drugs act on, and it’s been shown to work in other cancer types where the particular target is more prevalent or in a higher proportion. And so we felt that if we could measure, detect all of these targets through genetic tests, then we could potentially allocate patients to these particular studies.”

It is hoped the findings from this study could help pancreatic cancer to be targeted at the molecular level, hopefully with better outcomes.

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