The original article link says:

1) FOLFIRINOX is composed of 5-FU, leucovorin, irinotecan and oxaliplatin.

2) NALIRIFOX is ... a combination of THREE previously approved pancreatic cancer drugs, liposomal irinotecan (Nal-IRI or Onivyde®), plus 5 fluorouracil (5-FU)/leucovorin and oxaliplatin.

Statement (2) seems to conflate "5 fluorouracil (5-FU)/leucovorin" as one drug, when they are actually distinct, as far as I can tell, with leucovorin being = folinic acid (same as the FOL in Folfirinox). Sounds like 4 drugs to me.

Lancet lists the NALIRIFOX ingredients and ratios here:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01366-1/fulltext
- liposomal irinotecan 50 mg/m2
- oxaliplatin 60 mg/m2
- leucovorin 400 mg/m2 (a.k.a. Folinic acid)
- fluorouracil 2400 mg/m2
which is 4 drugs according to my math

This article compares original and modified Folfirinox:
https://jgo.amegroups.org/article/view/20784/17301
Standard FOLFIRINOX consisted of
- Oxaliplatin 85 mg/m2 IV infused over 120 minutes
- Irinotecan 180 mg/m2 IV infused over 90 minutes
- Folinic Acid 400 mg/m2 IV infused over 30 minutes (a.k.a leucovorin)
- 5-Fluorouracil 400 mg/m2 IV in bolus infusion and 5-Fluorouracil 2,400 mg/m2 IV in continuous infusion over 46 hours.

Modified FOLFIRINOX consisted of
- Oxaliplatin 50–85 mg/m2
- Irinotecan 60–180 mg/m2
- Folinic Acid 0–400 mg/m2 (a.k.a leucovorin)
- bolus 5-Fluorouracil 0–400 mg/m2 and continuous infusion 5-Fluorouracil 1,800–2,400 mg/m2.

So, it sounds to me like the main difference between NALIRIFOX and mFOLFIRINOX is just the replacement of old-fashioned Irinotecan with Liposomal Irinotecan.

I have no medical training, so forgive my confusion about why the creators of NALIRIFOX did their study comparing it against Gemcitabine + Abraxane when mFOLFIRINOX is already known to be superior to (G+A) and they could have done a perfectly comprehensible study with only one experimental variable against mFOLFIRINOX instead.

If NALIRIFOX is superior to mFOLFIRINOX, then great -- we have a new champion. If it's only shown to be better than G+A, which is already inferior to mFOLFIRINOX, what's the point?

I was also confused about the text citing NALIRIFOX as a treatment for metastatic PC. Shouldn't it also be considered an option in NON-metastatic PC, as mFOLFIRINOX and G+A already are?

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And just for clarity, I was a little thrown off by @stageivsurvivor 's comment "What makes THIS drug combination unique is the nab-Paclitaxel."

It's a little ambiguous whether "THIS drug combination" is referring to the new one (NALIRIFOX which seems to be touted as unique) or to the SoC treatment of Gemzar/Abraxane.

nab-Paclitaxel is the same thing as Abraxane, so in the above context, the G+A would be the 'unique' combination rather than the subject drug of this article (NALIRIFOX).

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In summary, I (lacking better biochemical understanding) am not yet impressed by this development.

As an academic side curiosity, I didn't get as much benefit from mFOLFIRINOX (which contains the platinum-based drug Oxaliplatin) as I have from G+A plus the platinum-based drug Cisplatin. Platinum-based drugs are believed to be effective in patients with ATM mutations (as I have). It's not an apples-to-apples comparison because of possible synergy with all the other drugs, but I wonder if the Cisplatin cocktail has worked better for me because of Cisplatin being a smaller molecule than Oxaliplatin, possibly penetrating better into the tumor. Fewer side effects as well. 🙂 I'd like to see a study of mFOLFIRINOX against "FOLFIRINcis" (Folfirinox replacing the Oxaliplatin with Cisplatin).