FDA approves new first line treatment option for metastatic pancreatic

Ok, so if I understand correctly, this can be tried if you haven’t tried any treatment at all for stage 3 or 4 diagnosis? or if you’ve tried the gem combo with a cancer that’s still progressing? Gives on average a couple more months - great news! Thank you for posting!

(m)Folfirinox is still the gold standard and used first in those patients age 70 or younger and a low ECOG physical assessment score of 0-1. When it begins to wane, Gemzar/Abraxane is the next first-line combination regimen used. If that doesn’t work or effectiveness decreases, Nalirifox gives the oncologist a third, first-line drug to use.

In clinical studies, Nalirifox was shown to be statistically more effective than Gemzar/Abraxane. Clinical studies on how it compares to (m)Folfirinox are not yet available. What makes this drug combination unique is the nab-Paclitaxel. It uses the Onyvide formulation which is liposome-coated nano particles of nab-Paclitaxel which get deep into the malignant cells and the “delivered payload” of drug is released. It results in greater and longer effectively.

A misconception people often have is in trying to understand clinical trial statistics. When it gets reported that the median of 3.4 months was observed, that doesn’t mean everyone is going to only get 3.4 months. There are patients who can be “statistical outliers”- those that received far greater benefit. Everyone has an equal chance of falling on the median, being to the left of it (shorter benefit) or to the right (long-term survivors).

Another thing to consider is that the study used the metric of 12 cycles (6 months). When (m)Folfirinox was compared to G/A, a 6 month period (12 cycles (m)FFX to 6 cycles G/A was used. Consider those patients who advocated for receiving more than 12 cycles of FFX. I did 46 cycles with 24 being FFX. Camille Moses did 37 cycles. Both of use are marking 12 years survival of stage IV disease. We advocated for more aggressive chemotherapy and far exceeded the median that was based on only doing standard of care 12 cycles.

There are other long-term patients whose stories are documented on PanCan.org, LetsWinPC.org. seenamagowitzfoundation.org and other sites. If you do standard of care, don’t expect more than standard results. I was physically strong and otherwise healthy and why I spoke up and advocated for going beyond standard of care.

One thing I have not been able to learn/understand is whether this development offers anything to patients undergoing treatment using one of the current first line chemo treatments. So, for example, if one was still at stable disease with G/A, would this be something that would be available if/when disease progresses? Or is it only a new first line option for those that have never been treated with any chemo? Anyone know the answer to that?

Thank you for that explanation. You answered a question I had, which was whether Nalirifox had been compared to Folfirinox (answer: no data at this point). You also explained how Onyvide (the liposomal irinotecan) works. To my totally untrained eye, I couldn't see much difference between Nalirifox and Folfirinox, and I still can't. I have an oncologist appointment tomorrow, and I'm going to ask about this. I'm doing quite well on my modified Folfiri, but I'm curious what this might mean for me. I also appreciate your comment re going beyond the standard-of-care 12 chemo cycles. I'm scheduled for cycle no. 20 next week, and we do not plan to stop.

Thanks for sharing your knowledge!

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).

I "think" those restrictions were just for the trial participants. They are saying this treatment is now "First Line". That would mean this would be the preferred or favored treatment for new cases of some pancreatic cancers, depending of course, on the doctors assessment in individual circumstances. I haven't read anything about recurrence with this new recommendation. Right now, it just seems to be the preferred initial treatment.

I am also stage IV and was diagnosed almost 2 yrs ago. I went 22 treatments of Folfirinox-a few w/o ironitecan and a few w/o oxilliplatin, but most full strength. Then after a year, my blood markers started slowly creeping up. While scans showed the tumor was stable and they could no longer find the spot on my liver, I contacted MSK and received high dose radiation and went 6 mos w/o chemo and no activity from the primary tumor. Unfortunately my follow up at the 6 mos point showed a tiny spot on my liver. While MSK and my local oncologist did not necessarily feel folfirinox failed, they suggested starting G/A to throw something different at the new spot. I’ve struggled a little with the G/A and had to stop chemo for about 4-5 weeks after the initial 2 back to back treatments (due to white cell and platelets dropping, irritable colon, as well as a family trip) and my docs felt it was ok since the spot was so small. CA19s really increased -from 1200 to over 3000. But scans still showed stable disease. I am back on G/A every other week at a 20% reduced dose.

Thankful that I still have no symptoms from cancer-just from chemo. And cancer seems to still be “stable”. With G/A, I seem to get almost IBS symptoms-some sessions worse than others- and wondering if this is causing my CA-19 to go up and down (heard inflammation can do that??) has anyone else had this happen?

Plan to ask my oncologist if this new treatment is something I could try. Also looking into clinical trials, Altho my oncologist also feels going back on Folfirinox may be an option if G/A doesn’t show good results.

So grateful for everyone’s input on this site. My goal is to be one of the outliers and trying to be as aggressive as my body can withstand.

Ditto the research commenters have done so far in helping us understand this new chemotherapy. I’m wondering @robee when you said you had G|A; does that mean you didn’t receive the cis? I’ve had 4 treatments so far and I’ve had my hair fall out, sensitive digestion (avoid spicy food and/or eating too much per meal is the remedy for me), and extreme nausea. I had 5FU post surgery last year and didn’t have any symptoms except hair thinning and some nausea for about 2-3 days however my cancer metastasized about 4.5 months after I completed my 12 cycles of 5FU. I’m 66 years old. I mention age since it appears to me from reading postings that age (and obviously health status) correlates with one’s ability to handle chemo. I ask about the cisplatin because it seems to be one of the ingredients that my cancer is slowly responding to. Obviously the type of mutations you have ate also relevant so I’ll mention that you have an atm like mutation and the TP53. I don’t see any postings from others about TP53 and mention it because I believe it’s one of the real buggar mutations that makes complete recovery a challenge.

Sorry for the Apple typo! I have the ATM like mutation or variant of base 40 and the TP53 mutation.

Hi. I’m 65 and have no other health issues and not even a family history of any type of cancer. They tell me this is “a fluke”. 😕 the hardest time for me was starting chemo while I had a severe bout of pancreatitis. Took months for me to feel like I was making headway.

Doing my best to stay on top of this but it is overwhelming at times. I try to push thru the chemo effects cuz I like being busy AND I feel better if I’m useful and productive. Can’t imagine actually working while dealing with this and those of you that do are my heroes!