To much fanfare and press coverage by the Pancreatic Cancer patient support foundations, the FDA on February 13, 2024, approved the liposomal Irinotecan (Onyvide) as a first line treatment of metastatic pancreatic cancer. The NAPOLI-3 study randomized 770 patients 1:1 to receive either 5 Fluorouracil (5 FU) plus Oxaliplatin (Ox) plus Liposomal irinotecan (NALFIRINOX) or to the control arm of nab-Paclitaxel plus Gemcitabine. There was improved progression free and overall survival for the NALFIRINOX arm.
But a closer look at the NAPOLI-3 trail trial leaves one a bit less enthused. It turns out the median survival of 11.1 months is exactly the same as the original FOLFIRINOX regimen that was first introduced 13 years ago in 2011 (Conroy, T. NEJM, 2011).
The only difference between the new NALFIRINOX and old FOLFIRINOX is the substitution of a different formulation of irinotecan as a nano-liposome which reflects a fat globule surrounding the irinotecan drug. The Oxaliplatin and 5-FU are unchanged. And Irinotecan is exactly the same chemical as its liposomal cousin. With survivals for both drug combinations identical, it is a little hard to see what all the hub-bub is about.
It is true that response rates and median time to progression were a tad better, but this could reflect improvements in supportive care and more experience delivering these types of therapies following the 13 years that have passed since FOLFIRINOX was first introduced.
As Albert Einstein said, “Insanity is doing the same thing over and over again and expecting a different result.”
What is most troubling is that 770 patients needed to be randomized to prove that FOLFIRINOX equals NALFIRINOX, with regard to the single most important measure, survival. At today’s prices it is unfathomable how much this trial cost to prove nothing.
An additional problem with the trial is that it pitted an old and less active chemotherapy doublet (nab-Paclitaxel plus Gemcitabine) against a FOLFIRINOX variant, when everyone already knew that FOLFIRINOX or its fraternal-twin would win.
Pancreatic cancer patients don’t need upbeat press releases from the organizations that claim to be supporting them or putting a favorable spin on trials like this. They need meaningful advances in the management of this highly lethal disease.
Each patient is unique in their sensitivity to drugs. By matching every patient’s tumor to the most active combination before they begin therapy, we can improve responses and survivals as we have already shown in Lung Cancer, Ovarian Cancer, Breast cancer, and other cancers. It is time to use this platform to improve the outcome for pancreatic cancer patients.
With five-year survivals for metastatic disease at 1-2% and unchanged in several decades, pancreatic cancer patients need something better and they need it now.