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Lucanix: A Vaccine Being Tested as a “Maintenance” Strategy in Advanced NSCLC

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Over the past several weeks, coincident with the opening of a new large clinical trial and some publicity associated with that, several people have asked me here about a lung cancer vaccine called Lucanix (full name belagenpumatucel-L, so a near guarantee that nobody will call this anything but Lucanix). My initial response was that I knew essentially nothing about it and more or less implied that there must not be much to it if there was really no buzz about it within the lung cancer community. But that’s a very simplistic view that goes against one of the issues I feel strongly about, namely that hype isn’t the same as promise. There are enough approaches that I’ve been critical of despite “buzz” (RFA, proton beam radiation, celebrex, just to name a few I’ve minimized over the past few weeks) that it would be completely hypocritical for me to suggest that a lack of attention from the media or lung cancer establishment means that a treatment isn’t worth pursuing. I’ve seen over the years that the interest in a treatment is a combination of the favorable findings from early work, the public relations machine and marketing muscle of the sponsor company, how explainable it is (we like a good “story”, so it’s easier to explain that something blocks EGFR or is antiangiogenic than that something is an aurora kinase inhibitor), and certainly some luck about what just happens to catch on. I’ve also been following some treatments that seem to get little traction despite quite encouraging results (talactoferrin alpha, for instance), probably because they’re products of small companies, and/or have been studied by people who don’t immediately attract media attention.

So it was only fair for me to review the available information about Lucanix and provide a more informed opinion. T0 their credit, folks at NovaRx, the company working on Lucanix, saw my comments announcing my intention to write a more educated piece, and they proactively sent me several files with background information about the company, Lucanix, and the trial being conducted now. After several attempts to connect, I spoke earlier today with Ms. Carissa Schumacher, Director of Corporate Development, and Dr. Habib Fakhrai, President; both were eager to discuss the promise and challenges of the early work with Lucanix and the new trial moving forward. I’ve never had the leadership of a company provide more enthusiastic and open communication, so kudos to them for that.

First, what is this vaccine? There are two main types of cancer vaccines. One type is called autologous and is generated from the individual patient’s tumor, which has the advantage of being tailored to the individual, but it requires tumor to be collected from a patient by a separate procedure. Lung cancer tumor tissue isn’t always accessible, so it’s a problem and involves some degree of risk to obtain tissue to generate the vaccine, which is also a time-consuming process. The other type is called allogeneic, which means that it’s made by other tumor cells, not those from the patient. Lucanix is a vaccine derived from four different lung cancer cell lines (two adeno, one squamous, one large cell), so the immune response would presumably be against proteins on any of a number of different lung cancers. This is combined with an “antisense” gene modification against transforming growth factor-B (or TGF-beta), which is a very complicated idea, but the net result is that this helps reinstate immunity against cancer cells after they had disarmed the body’s surveillance system in the immediate area around the tumor with this protein.

This work was first reported at an oral presentation at ASCO in 2006 (abstract here) and then published in the Journal of Clinical Oncology, one of our leading journals, that same year (abstract here). It included 75 patients with anywhere from stage II to IV NSCLC, although nearly all had stage IIIB or IV disease, and most had received prior therapy. Patients were then randomized into three different dose levels of the vaccine, which was administered into the skin (intradermal) once every 1-2 months. Not surprisingly, the vaccine was associated with minimal side effects. While fatigue, pain, and pulmonary symptoms were reported, there was no real indication that this was from the treatment and not the cancer itself. Two patients had significant issues felt possibly or probably related to the vaccine: one had fairly significant pain and swelling around the injection site on one occasion, and another developed chronic myelogenous leukemia (CML) 5 months after 16 full cycles of the vaccine — it remains unclear if the vaccine caused this or whether this was just a coincidence.

In terms of responses among patients with measurable disease, 6 were seen among 40 patients, with 5 in the middle or highest dose. A total of 59% had no progression after 16 weeks on treatment. However, looking at several of their highlight responses, I’ve seen far more convincing responses, and I just don’t feel completely confident that these aren’t improving pneumonitis, infection, or some other non-cancer process, at least in some of these patients. Apparently the physicians involved in the trial were convinced that these were true responses, but I’d really like to see a broader array of data to really be convinced that this can lead to tumors shrinking.

Survival certainly appeared promising, particularly compared to historical data of what you’d expect for previously treated patients. Median survival was 14.4 months on the trial, and it was actually 15-16 months in the two higher dose cohorts, in which the two year survival was about 40%:

Lucanix survival (click to enlarge)

I do find it hard to explain why the lower dose would do visibly better than the middle dose, and my honest sense is that this is because the trial involves a small number of patients, so random chance of the particular characteristics of a few patients and their cancers play a large role. I’ve been impressed that some of the most unusually healthy patients with the most indolent lung cancer I’ve ever seen are the ones who jump on a plane to Dallas to enroll on these trials led by Dr. John Nemunaitis at Baylor, who runs multiple vaccine-based trials — because of this, I think it will be very important to rule out selection bias of remarkably unusual patients as a reason that these patients did so much better than we expect to see in large trials of previously treated patients. in fact, the reported “tumor burden” (basically, the size of measured disease) was very low in their responding patients, so I wonder if many of these patients had far less aggressive disease than a more average population that would be reflected in results from larger trials. But perhaps suggesting a real benefit, responses on scans were correlated with better immune responses in patients on the trial.

On further review of the data, results seemed best among patients who had achieved stable disease or better on prior treatment (although it’s pretty much this way with every treatment — “responders respond“). Combined with the rest of the findings, this led to development of a phase III clinical trial with up to 700 patients who have received prior chemo for advanced NSCLC and shown stable disease or better after first line treatment to then be randomized to active vaccine or placebo (50% chance of each). This trial is just getting started now (more information here). While I do think this approach is promising enough to be worth testing in a larger setting, and I think the early results desperately need to be compared to a control arm in a randomized trial to separate true treatment effect from the strong possibility of selection bias, I think this will be a very hard trial to complete. First, placebo-controlled trials are the easiest to interpret and “purest” in design, but the fact is that many patients are reluctant to enroll, especially American patients, because they express an extreme aversion to being potentially randomized to a placebo. While it is ethically permissible to offer a placebo in a setting of “maintenance” where it’s not yet a standard to do anything but follow a patient who has shown a response or stable disease after first line therapy, I’ve written that I believe that the evidence is compelling enough that I would now be inclined to recommend an immediate transition from first line to second line treatment (see prior post). Finally, I think it will be challenging to get enough patients enrolled who have shown stable disease or responded to first line therapy and are now off of treatment, not yet on second line therapy, and not yet progressing. That’s really threading a needle, and trials that have had such a narrow window for enrollment have had a very difficult time accruing patients.

That said, this work looks intriguing enough that I really hope I’m wrong, that many patients are interested in enrolling and the trial accrues quickly. I’d be interested to hear whether people here would be willing to enroll on such a trial, or whether they would be unwilling to subject themselves to be randomized to a placebo in the maintenance setting after first line treatment.


22 Responses to Lucanix: A Vaccine Being Tested as a “Maintenance” Strategy in Advanced NSCLC

  • Hig says:

    Five years ago diagnosed with stage III-IV nsclc. Carbo/taxo in late 2003/early 2004; right lobe wedge resections April 2004; NED until Sept 2006; upper left lobe removed Oct 2006; some delay in recovery due to fistula; started Tarceva Mar 2007; some progression Dec 2007; started Carbo/Taxo/Avastin Jan 2008; good results started maintenance Avastin May 2008; PET due soon. Am doing well, still very active, softball, tennis, basketball, hiking, etc. Yet the big question, with all that behind me, is WHAT NEXT? If there were no other viable options (and I don’t know of any) I would be willing to take a 50/50 chance.
    Hig

  • Dr. West says:

    Hig,

    I have written about several other treatments that have been tested and are recognized as being potentially effective for patients previously treated for advanced NSCLC. In addition to tarceva, both alimta (at least for patients with non-squamous cancers) and taxotere are widely used and FDA-approved for this setting.

    I appreciate your thoughts on a 50/50 chance being better than no other option. To me, the bigger issue is that there are other options for patients who have only received first line therapy, so I am concerned that many people would not accept a randomization to potential placebo in this situation.

    -Dr. West

  • magbag says:

    My son is 36 and was diagnosed with nsclc stage 4 in april 2008. He responded well to 6 cycles of cisplatin,gemzar and avastin. He is still having th avastin 3 weekly. He did not have any surery. He is doing very well. I am interested in the lucanix trial, even though it is a double blind placebo trial. I feel a 50/50 chance of 30-40 months progression free survival is better than an extra 2 months progression free with the avastin. I am interested in your view on this especially what could be our other options. Thankyou for your help. Maggie

  • Dr. West says:

    I think it’s a stretch to presume that there will be a 30-40 month progression-free survival on the lucanix arm. That may have been reported based on a few patients in an early trial, but I’d consider it extremely unlikely that these kind of results will really be seen in a larger, multi-institutional trial. The reason it’s got a placebo control arm is because we think there’s a real chance that the vaccine will actually prove to be no better than a placebo, or even do worse (I wouldn’t consider that likely). Larger trials almost always provide less impressive results than the smaller ones that preceded them.

    I still think it’s a reasonable option and that the vaccine and trial are promising concepts. I’d be very eager to see the study completed and learn whether the vaccine proves to be another effective tool in treating lung cancer.

    -Dr. West

  • bayrealtor says:

    Hello Dr. West!
    Seems there is a buzz going on right now about lucanix. In previous posts I discussed my wifes case 35, asain non smoker with nscls 1st line was carbo/taxol & avastin, saw good results….changed to alimta due to low white blood cells on carbo, saw progression on alimta /avastin, now
    on tarceva for 3 months with “dramatic improvement” in both lungs. Do you think she would qualify for this trail and do you think the vaccine may take away from the tarceva? She also has avastin once every three weeks based on a study showing avastin & tarceva have better results than tarceva alone. Is the avastin considered chemo that would exclude her, how about the tarceva? Would she be able to continue tarceva while on the trail? Lots of questions but again, we trust and hold your opinion in high regard.
    Bill & Cathy

  • Dr. West says:

    I’m not participating in the trial, so I don’t have all of the details. It is meant for people to start immediately after chemo, and I think there is essentially no chance that someone would be able to be on other standard anti-cancer therapies, such as tarceva and/or avastin, at the same time.

    I would also say that there is much more buzz about lucanix in the lay media and general public than within the lung cancer/oncology professional community, which is more skeptical. I also think that this trial is going to be extremely difficult to complete, so I’m afraid we may never get a firm answer from it.

    -Dr. West

  • kentsjolund says:

    Dear Dr West,

    I appreciate your candor without leading folks down the “bad rabbit hole” i.e. “look how low the survival rate is.”
    I really liked your comment “although it’s pretty much this way with every treatment — “responders respond.“
    A large part of my survival mentality and strategy is that MY cancer and MY fitness going into this are different that everyone else’s and I know there is ALWAYS someone on the right side of the survival curve.!!

    I am applying to the LUCANIX trial but I am checking to see IF I have the critical protein (MAGE-3) in my tumor. I am 51 and retired military so have a lifetime of good health and fitness so should be a good candidate.

    I am on the standard first line therapy ALIMTA/CICPLATIN/AVASTIN and scheduled for 7 at 21-day intervals.

    Here is the real question; I have seen your posts and interested in your opinion; I really like the mushroom as it is used WITH western medicine (chemo and radiation) in JAPAN right now:
    I am taking two herbals (dropped IP 6 because of possible interference w chemo)
    http://www.naturalnews.com/025455.html
    http://www.pawpawresearch.com/pawpawworks.htm
    Very Respectfully
    Kent Sjolund

  • Dr West says:

    I don’t think there is any information out there to speak to your question specifically. To my knowledge, no study has ever reported on this issue. Certainly, I don’t have a good sense of this. My bias is against adding treatments that aren’t well studied and are based on unsubstantiated claims based on a presumed mechanism. Many ideas with a compelling rationale have failed completely when tested in clinical trials, and some have even demonstrated a harmful effect.

  • JimC says:

    As you know, Dr. West has addressed the subject of pawpaw recently in this thread: http://cancergrace.org/forums/index.php?topic=5304.msg33266#msg33266 “I don’t really have any additional insight I can provide. I’m glad Dr. Bufi could comment on PAW PAW, since it’s really not an agent for which I am very familiar with the data.”

    And Dr. Sanborn had this to say regarding mushrooms: “I have not heard of this specific mushroom [Agaricus Blazei Murill], but what I would say is that in the vast array of supplements that patients take, one of those that I have run into the most trouble with are the mushrooms and mushroom complexes. I have seen patients with abnormal (and even sky-high) liver tests when taking mushroom complexes of different types, in a way that has interfered with our ability to give chemotherapy. I have also seen these liver tests normalize after a patient stops taking them. I have consequently been very concerned about patients taking mushrooms of different types (other than the standard mushrooms in the course of a normal diet) while they are receiving any type of chemotherapy.”
    http://cancergrace.org/forums/index.php?topic=2608.msg15462#msg15462

    Jim

    Jim

  • JoeSperrazza says:

    Kent,

    Jim, Ned & Dr. West responded to your question about Paw Paw here:
    http://cancergrace.org/forums/index.php?topic=5304.msg33286#msg33286

  • randyleepublic says:

    What about a patient with a stable adenocarcinoma who has had no treatment? Wouldn’t it make more sense for such an individual to first try Lucanix than to use Lucanix after chemo? After all, for Lucanix to work, the patient’s immune system must be functional, but chemo harms the immune system, does it not?

  • Dr West says:

    I agree that an immunotherapy has a more compelling rationale if someone isn’t significantly immunocompromised. However, it’s really hard to interpret what the immunotherapy is doing on someone who has a stable cancer with no prior therapy. We know that some cancers are very indolent and may remain more or less stable for years, so if someone demonstrates ongoing stability on Lucanix or Dr. West’s magic elixer or ketchup, is it because the intervention is causing the stability, or would any intervention look good by showing stability because the cancer may well remain stable on its own for a very long time?

    If you wanted to give Lucanix to treatment-naive patients as initial “window of opportunity” therapy and closely monitor them for progression, switching immediately to a proven therapy in the event of progression, that might be feasible (though you’d run the very real risk of that some patients would progress significantly and decline clinically on investigational treatment, perhaps missing their chance with an established first line therapy). But otherwise, focusing on a patient population with an unusually favorable natural history creates the kind of selection bias that has historically made us skeptical of immunotherapies because they look good in highly selected populations, then fail in a larger trial setting.

    -Dr. West

  • randyleepublic says:

    Thanks for your reply Dr. West. I apologize for this, but I have to point something out to you: I don’t give a damn about proving anything! What I want to do is secure for myself my best chance for survival. I understand what you point out as the risk, however that seems to me to be less of a risk for my case in that I am not seeing any progression even without Lucanix, than doing conventional treatment with it’s poor long term survival rates. How do I get a compassionate use licence for Lucanix?

  • Dr West says:

    I appreciate that, but I would point out that there is no actual good evidence that getting Lucanix right now will help you live a day longer, so I would question why anyone would want to move the moon and stars to get it. People were just as laser-like in their focus on Stimuvax and many other treatments that have proven to be ineffective before the well-done studies actually showed that they don’t help.

    Having a compassionate use program implies that the therapy is proven to be beneficial. In the case of Lucanix, I consider it a vehicle for driving hype.

    Yes, I know that Lucanix has looked good in a few dozen patients, as have many other treatments that looked amazing until they were tested thoroughly. I believe that your question will make sense if/when Lucanix is actually proven to be beneficial, but until then, I don’t want to just feed faith-based hype.

  • texandave says:

    Dr. West – as always, I appreciate your thoughts. It is a little concerning that you are sounding just a little more skeptical than cautious. You have pointed out that the research subjects have had stable disease and/or significant response to treatment prior to using Lucanix. The analogy that I have compared it to is kicking a bully on the ground when he is knocked out cold. At the same time, maybe Lucanix works as a “stabilizer” when things are in clear remission. At least that is what, at the least, many of us are hoping for that – at the least, as again we want more available tools in the treatment arsenal. The side effects compared to chemo and radiation sure generate some appeal as well, The Stimuvax results, so far, were disappointing but make us more realistic. It is worrisome when you note in discussing this drug with terms like hype and magic elixir. You have been for many of us a go-to doctor for solid information. Is there any part of you, in what you have read and your past experience, that thinks Lucanix just may some role down the road and should not be written off. After all, it is wrapping up phase III and the ancedotal information – for the better part – doesn’t seem to be diminishing hope. Again, thank you for all you do.

  • Dr West says:

    I actually just did a video on “what do the negative results from the START trial with Stimuvax mean?” that summarizes what I consider my view on this issue. I really dislike when there’s irrational exuberance and a frenzy around a treatment, and I think that many immunotherapies are prone to this, but also that some companies go out of their way to fan the flames… I think that’s been the case with Lucanix, and it pushes me more into the direction of trying to combat manipulation. I don’t mean to have unjustified skepticism, but I may reflexively push into that direction to counter what I think is a tide pulling in the direction of putting too much faith in early results.

    But at the same time, I also specifically addressed in the video the question of “knowing that the Stimuvax trial failed, does this mean that we should expect failure from other immunotherapies, like Lucanix or MAGE-A3?”. And I definitely feel we shouldn’t throw out the baby with the bathwater and presume all immunotherapies are ineffective against lung cancer. These are different treatments, and a negative result with Stimuvax means nothing more and nothing less. I’m still hopeful that MAGE-A3 and/or Lucanix could produce positive results in their phase III studies, and I’m also hopeful that one or more of these approaches, and/or anti-PD1/anti-PD-L1 immunotherapy will prove beneficial enough to be added to our armamentarium against lung cancer in the next few years. So I’m not that skeptical, but I don’t think it’s fair or appropriate to presume that Lucanix is beneficial or fair based on phase II data. And if you go on Lucanix and do well, I think there’s good reason that what will be conveyed loudly to the rest of the world is that Lucanix was the linchpin to your success, even if you would have done every bit as well on nothing at all. And it’s even possible that Lucanix will prove to be harmful. I think that having patients who are likely to do well with no therapy continue to do well, praise Lucanix for their ongoing success, and lead others to seek Lucanix like it’s the key to salvation is irresponsible medicine.

    What I’m saying is that I’m completely open to the randomized trial data, and that trial is done. If it’s positive, I’ll be very happy — I won’t consider it too good to be true, and I’ll champion the treatment. I’m just not going to call it a winner and act as if that’s the case before then.

    -Dr. West

  • Dr West says:

    You also make a point about not really caring about knowing what’s right as much as doing well personally. That’s fine (and I applaud your transparency and forthright style), but we all need to recognize that we all have our biases. My bias is to not practice irresponsible medicine and give potentially ineffective and/or expensive treatments to people, while your bias is to pursue maximal benefit but not to prioritize efficient use of societal resources. I don’t mean to imply that one view is inherently better than another, but rather that we can’t divorce ourselves from the biases we come in with, and they aren’t the same.

    -Dr. West

  • randyleepublic says:

    That is fine that we all have our biases, and we should all be honest about them. Unfortunately for me, the biases of the medical establishment have profoundly negative impacts upon my life. Whereas my biases only affect me. This asymmetry seems profoundly unjust, but no one cares much. Oh well.

  • Dr West says:

    I would counter that your statement that the medical establishment is causing a profound negative impact on your life but that your biases affect only you ignore several key points:

    1) You are presuming without real evidence that Lucanix is significantly effective and associated with a survival benefit. That hasn’t been shown, and I would remind you that plenty of people have been similarly wildly optimistic about Stimuvax, which was recently shown to actually be ineffective in improving survival.

    2) You are suggesting that Lucanix or any other treatment you might want to self-prescribe is going to improve your particular outcome, when you have a cancer that you have described as extremely indolent. There is plenty of reason to believe that the only thing someone with an extremely indolent cancer will experience from treatment is side effects. I would submit that it’s a leap for you to presume that your cancer is a clear threat to your survival if it hasn’t progressed significantly over the time you’ve been following it, and the evidence suggests it’s a very indolent process.

    3) You are saying that your extreme desire to obtain Lucanix will impact nobody else, but highlighting a desperate plea for it on a public forum could easily give someone the mistaken impression that it actually has some established value and that they should seek it out. Moreover, if you continue to do as well as you likely would with no intervention but happen to pursue Lucanix, I think there’s good reason that you would make very public statements that you’re doing well and presume or state that it’s because of the Lucanix. This would very possibly if not likely feed a frenzy of plenty of other people demanding a treatment that has no proven value and may be harmful, especially if people reject a more established treatment for their particular case because they internalize a view based on no good evidence that Lucanix is extremely valuable.

    If that seems far-fetched, just do an internet search for “DCA” and see the striking gulf between frenzied desire for a purported cancer treatment and the conspicuous absence of any actual good evidence of a clinically beneficial intervention (I mean, besides the anecdotal “my wife was told she has 3 months to live, and now she’s alive 2 years later and doing fine on DCA” that is the cornerstone of all treatment approaches that don’t stand up to actual scrutiny but attract a mob following of zealots).

    I would counter that the medical establishment is not doing you any harm and that your machinations are not completely without consequence to other people.

  • randyleepublic says:

    >> 1) You are presuming without real evidence that Lucanix is significantly effective and associated with a survival benefit. That hasn’t been shown, and I would remind you that plenty of people have been similarly wildly optimistic about Stimuvax, which was recently shown to actually be ineffective in improving survival.

    No Sir! You are presuming that you know what I believe. In fact, I have no presumptions about Lucanix. What I *know* about Lucanix is that it has been tested for side effects. The evidence very strongly suggests that it has none. That being the case, I would like to try it. That I am denied the opportunity to effectuate a very personal decision, and for no *good* reason is a crime against me! If I was not denied Lucanix, then the possibility that others might misinterpret my experience being used as a reason to deny me the right to make this decision is the height of dehumanizing arrogance!

    I don’t apologize for this assertion, but I do admit that we are surrounded and inundated with equivalent experiences on an hourly basis in modern America, so I understand that most of us are blind to the insult. I am sorry that you have become so conditioned. It is a tragedy.

  • texandave says:

    randyleepublic, you noted that what you have read about Lucanix suggests that it has no side effects. I have read similiar information, including a lot of lay information that notes the “only” side effect as being redness at the injection. YET side effects are still reviewed and noted on a much larger phase III trial. Recently, another drug for LC tested in another country at phase III level had testing stopped in mid-phase because side effect issues outweighed the therapeutic effects. Drug companies play a finesse game to get from phase II to phase III – with the millions invested and potentially coming up bust, it is understandable. Phase III remains the standard – and then a physician is required (by ethics and standards of care) to decide if the known benefits of a drug outweigh the potential risk. Now – don’t get me wrong – I want Lucanix to have an incredibly successful phase III, so bad I can taste it. There is just a eat that things have to unfold.

  • texandave says:

    Sorry – error at end of post – “eat” should be corrected to “way”.

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