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Let's not forget the buzz created at ASCO
The PR did come out of nowhere. Sure wasn't expecting it so soon after ASCO. But it did answer the $64 question on Direct! Huge!
NWBO is a trendsetter. INO responds to AF article. Can you imagine if every trash article by AF is matched by a corresponding one from the trashed company.
Koman, per your quote
“Well my hypothesis is that the problem in these patients isn't that they don't have an immune response to their cancer but that these immune response is being down regulated so having 6 immunization doses or even more will not make any difference for the majority of these patients”
Well wasn’t that the $64 question for all of us? We all had concerns that the pre-clinical animal studies, showing injection of partially mature dendritic cells resulting in eradication of tumors, would translate to humans. I would not have been surprised if this P1 study was a dud. After all, the junkyard is full of fantastic animal studies that did not translate into successful clinical studies. So when Evaluate states
“Not sure why there are some folks who do not find the very initial, very premature Direct results stunning. I did not expect anything huge, but was hopeful to hear something promising (since LP indicated that they were encouraged by early results seen). Over 50% of patients appear to have some response! And this result is after only receiving half of the treatments! And after such a short amount of time since initial injection! And both local & systemic results seen! And all of this in patients that have ZERO other effective treatments to choose from. And these patients have all been through a slew of other prior treatments that may have effected (harmed) their immune system.”,
I too found DCVax-D results pretty big. I am comfortable in believing that DCVax-Direct will be a success and that it circumvents the down regulation in humans as they saw in animals. I did not believe that before NWBO provided us these preliminary results. Don’t get me wrong, I’m not expecting the 80 - 100% eradication that they saw in animals, but it will be a go to tool in the war against solid tumors. So for me, positive Preliminary results + great animal results = Positive clinical results. The $64 question is being answered regarding Direct and I am looking forward to future updates from Northwest.
Theel, I love this post. Your quote
“AF and the Street have put out nearly daily articles bashing the company. Why? What on earth for? It sure seems like overkill for a company that has very little chance of getting their treatment eventually approved by the FDA.”
Wow! That really hit home for me. The only reason I can think of is that AF and his buddies are really scared of lil’ ole NWBO.
You’re not going to believe this, rather, more appropriately, I wouldn’t have believed in opening up the post that I would understand the logic but I did! I’ve worked w std dev up to the wazoo so when put in the context of smaller sample size (events) increases the likely hood of a larger standard deviation and that a higher std Dev (i.e. variation) leads to a higher p value I get that. Thank you for the explanation.
Hi Pyrr, in reading your statement
A little late to the party but I’d be remiss in not saying Great Job! For what’s it worth, I wrote a comment I was hoping to post in regards to an article yesterday in the NY Times by Andrew Pollack titled “New System for Treating Cancer Seen as Hopeful” that discusses immunotherapy, and of course, mentions the big pharma players. In my comment, I mentioned NWBO, DCVax-L and cited your article but when I went to post it there wasn’t anywhere to post a comment where more often than not there is. Oh well.
“just re-inject your own blood
back into you”
That's AFs next post. You could have
had him and his buddies
figure it out on their own!
I have had Celldex on my watch list since it was still in the womb of Medarex, a company whose antibody tech I really loved and which I owned. Prior to naming the company Celldex, while still in the womb, it was being referred to as Keycell (key-in-a-cell) Therapeutics which had to do w targeting antigens to receptors on antigen-presenting cells (APCs). Ok, I digress, that’s not the point of this post. The point is that Celldex was wallowing in the under $3 per share range 2 or so years ago before it shot up to 35 on Phase 2 results. What happens when DCVax-L P3 results come out or DCVax-D P1 results come out that shows Phase 2 type efficacy? Just a matter of a little time which will arrive before we know it.
Not a bad article. Touches on most stuff. I can see giving this to someone unfamiliar w NWBO to help them get their arms around what they are about.
Great Qs. You had some more good ones in post 10444.
“It's not inconceivable that "the dog ate my homework" at a site”
This popped into my mind a few times over the course of the last few months but thinking about it I think it’s harder to do than it sounds. What raw data could be lost? Patient consent info, Initial blood draw, sending blood to Manufacturing for processing and return to clinic, patient injections, and patient follow-up leading to events. Even if you are missing some of this data, I would think you should be able to reconstruct the data. But regardless if you did or did not misplace data, I think this is a pretty hard thing to do. It would take special talent to mess that up. It’s not like you mixed up placebo and vaccine, oh, wait a minute, there is a placebo. I don’t think that would have happened either since to have a major effect (all clinical sites), the problem would have needed to come from manufacturing. But I get the impression manufacturing is on top of things.
See Longusa's post 3776. From the post
Hey Pyrr…Nice. Here’s just a couple of minor editing changes. Feel free to throw them in the garbage.
- “That's right, anywhere, including in the brain, in the liver, in the pancreas, in the colon, in the lung--literally anywhere.”
“That's right, anywhere, including in the brain, liver, pancreas, colon, lung--literally anywhere.”
- "activated" (with proprietary company technology)
- “The far more likely scenario is that, just as seen in the Triozzi study, 100% response rate will eventually be reported in the DCVax-Direct trial. What has not been seen to date with an intratumorally injected DC vaccine is zero response. In fact, as a broad category, intratumoral injection has always proved effective. The problem has been poor tolerability in using synthetic, toxic and therefore harmful substances, such as seen here. This is not the case with the abundantly homogeneous DC vaccines.”
Regarding, “The far more likely scenario is that, just as seen in the Triozzi study, 100% response rate will eventually be reported in the DCVax-Direct trial.”, while most on this message board are comfortable w this statement, you are setting yourself up with nasty comments from those more skeptical. I would state something akin to - The far more likely scenario is that, similar to the Triozzi study, large (or strong or perceptible, etc) response rate will eventually be reported in the DCVax-Direct trial.”
Regarding, “The problem has been poor tolerability in using synthetic, toxic and therefore harmful substances, such as seen here” “such as seen here” seems ambiguous.
That’s as far as I got, need to run out. Again, excellent article, summarizes it nicely, and feel free to place these comments in the garbage.
Thanks for the feedback. I think I merged/mixed up 2 different message treads you were discussing; one on Labeling changes for different cancer types and the other on “manufacturing “ changes on DC enhancement. Lot of good info here.
I’m a day or so behind in reading messages so pardon if this is discussed in another post. I lumped a couple of your posts together. This quote is from your previous post
“DCVax-L" could be the basis for their (assuming approval) sBLA for "all cancers”
When I was reading your message, I was saying to myself this isn’t right - adding a new indication necessitates running some clinical studies to confirm the change. But Linda did say what she said at the March 27 webcast which I extracted from 1 of your posts.
“All operable tumors can be treated with DCVax-L across multiple cancer types without the need for further trials. It will eventually be used in all cancer types with same technology—no need to start over with various trials—“After that [current ph. III trial], we will then take it into other types of solid tumor cancers, and a real advantage will be that it’s the same product made in the same way, just using biomarkers from tumor tissue from a different location in the body, and THAT means that each of the further cancers is just a label extension. It’s not starting all over again with ph.I trials and so forth.”
I didn’t listen to the webcast but I assume “and so forth” also means P2/3 studies? Also wondering if the initial indication would include “all solid tumors’ instead of a sNDA for each new indication? Also, if the initial BLA is for GBM, and they want to change the label to include new indications, I would think that’s a major, major change. Per the FDA guidance under labeling (p.24)
Major Changes (Prior Approval Supplement)
…The following list contains some examples of changes currently considered by CDER to fall into this reporting category.
Changes based on postmarketing study results, including, but not limited to, labeling changes associated with new indications and usage.
OK, I started reading newer posts and it looks like this is being discussed.
I’m a day or so behind in reading messages so pardon if this is discussed in another post. I lumped a couple of your posts together. This quote is from your previous post
“DCVax-L" could be the basis for their (assuming approval) sBLA for "all cancers”
When I was reading your message, I was saying to myself this isn’t right - adding a new indication necessitates running some clinical studies to confirm the change. But Linda did say what she said at the March 27 webcast which I extracted from 1 of your posts.
“All operable tumors can be treated with DCVax-L across multiple cancer types without the need for further trials. It will eventually be used in all cancer types with same technology—no need to start over with various trials—“After that [current ph. III trial], we will then take it into other types of solid tumor cancers, and a real advantage will be that it’s the same product made in the same way, just using biomarkers from tumor tissue from a different location in the body, and THAT means that each of the further cancers is just a label extension. It’s not starting all over again with ph.I trials and so forth.”
I didn’t listen to the webcast but I assume “and so forth” also means P2/3 studies? Also wondering if the initial indication would include “all solid tumors’ instead of a sNDA for each new indication? Also, if the initial BLA is for GBM, and they want to change the label to include new indications, I would think that’s a major, major change. Per the FDA guidance under labeling (p.24)
Major Changes (Prior Approval Supplement)
…The following list contains some examples of changes currently considered by CDER to fall into this reporting category.
Changes based on postmarketing study results, including, but not limited to, labeling changes associated with new indications and usage.
Yep, I think you nailed it on the head! He's kind of multi-tasking in a way.
Pyrr,
Regarding
Quote:
I'm shocked that when you plunge a giant needle four times into a tumor mass, then take a scan of that tumor mass, you find damage. -AF
I just envision AF saying to himself what is the most stupidest thing I can say that people will still take me seriously. He and his buddies must be having quite a chuckle that they think they are getting away with that one. Like throwing mud at the side of the barn and seeing if it sticks.
Yes, this is huge. This answers the $64 question, and that is, “Will DCVAX-Direct, which showed dramatic results in mice, work in humans?” And the answer is a resounding Yes! Maybe it’s the $64 Billion question? All I know is I am going to get a kick at watching the shorts squirm in the following days and months especially AF! I do have to say there was a little mystery this morning wondering if AF was going to put out a hatchet job or mea culpa but I should have known.
"Such early indications in such a difficult and advanced stage of metastatic cancer are encouraging."
In a difficult and advance stage...least we forget!
Hey Pyrrhonian, first I should tell you, that what I posted in my previous post is from experience in carrying out routine Good Manufacturing Practice in the industry; never really involved in the back and forth dealings w the FDA. As an individual biotech investor who has lots to learn, I like to give it a 3 - 6 month interval between end of study and application submission. I believe “He who should not be named” (AF) once said 3 months from end of study but I would think getting accelerated approval might be more involved. Sorry I couldn’t be more helpful than that.
Pyrrhonian, in regards to “much of the BLA, especially in regard to manufacturing, was already hashed out in the "thousands of pages of documentation" that Linda referred to during the Feb talk” I believe is routine and normal. You start out w an IND that includes a Chemistry, Manufacturing and Controls section. Every year as you tweak the manufacturing process you record those changes in an Annual Report and that’s what you start out with in your BLA. It goes without saying that you better make sure your Is are dotted and Ts crossed if you don’t want to delay the process.
I am familiar w the exposeadam site since what you see on the site is doing what Adam does best i.e trashing a stock but in this case w Spectrum Pharma which is one of my main holdings. His articles loaded w quarter truths and conjecture, would be timed,always, when good news came out on the stock just like he's doing now w NWBO. Over the years, AF has done this so much that I'm always amazed that his two bit articles can affect a stock, at least for a day or two.
Just to add a little to the body of evidence being gathered. From
Sacher AG, et al "Shifting patterns in the interpretation of phase III clinical trial outcomes in advanced non-small cell lung cancer: The bar is dropping" J Clin Oncol 2014; DOI: 10.1200/JCO.2013.52.7804.
Results ... Although overall survival remains the most common primary end point of phase III trials, more trials from the last decade have used progression-free survival instead (none in 1980 to 1990, 13% in 2001 to 2010; P = .002...
Conclusion A significant shift has occurred over the past three decades in the design and interpretation of phase III trials in advanced NSCLC. The use of survival as the primary measure of benefit is declining, as is the magnitude of benefit deemed clinically relevant.
Hi all, been following this board for months (switched from Yahoo after the Fox videos came out) but first time posting since it took me time to get a reasonable # of shares and did not feel putting up my 2 cents was warranted w/o shares. Pasted this from medpage regarding standard of care for GBM and may have some interest; it summarizes a study that was in the New England J. of Med. I’m a little behind in checking the board so pardon me if this is already posted.
No Survival Benefit for Avastin in Glioblastoma Published: Feb 19, 2014 By Charles Bankhead, Staff Writer, MedPage Today
First-line therapy for glioblastoma remained unchanged after two randomized trials showed no advantage to adding bevacizumab (Avastin) to the mix.
A multicenter international trial showed a statistically significant 4-month improvement in progression-free survival (PFS) but no difference in the co-primary endpoint of overall survival among patients treated with radiation therapy, temozolomide (Temodar), and either bevacizumab or placebo.
A larger trial with a similar design also found that the addition of bevacizumab was associated with a numerical improvement in PFS but not overall survival, as previously reported. The trials were published simultaneously in the New England Journal of Medicine.
The results add to those of previous trials that "have not been very revealing" in terms of bevacizumab's effect on overall survival in newly diagnosed glioblastoma. How the results influence future investigation of the drug in glioblastoma remains to be seen, said Mark R. Gilbert, MD, principal investigator of the larger trial.
"Currently, we have no data to support use in front-line therapy," Gilbert, of the University of Texas MD Anderson Cancer Center in Houston, told MedPage Today. "In the recurrent situation, patient characteristics are very different. Patients typically have large, fairly rapidly growing tumors. The patient populations tested in these studies were predominantly patients who had extensive tumor resection.
"Bevacizumab may be better in patients who have large, bulky tumors as opposed to trying to prevent regrowth of tumors that have been extensively removed."
Investigators in the international trial noted that the bevacizumab arm maintained baseline performance status for a longer period of time, although the targeted agent was associated with more adverse events, including grade =3 adverse events.
Standard of care for newly diagnosed glioblastoma consists of chemoradiation with temozolomide, followed by temozolomide maintenance. Bevacizumab has FDA approval as second-line therapy.
Several phase II trials suggested a survival benefit with the addition of the angiogenesis inhibitor to standard first-line therapy, leading to separate randomized clinical trials, one involving investigators at 120 sites in 23 countries and the other based in the U.S. and coordinated by the Radiation Therapy Oncology Group (RTOG).
The international trial involved 458 patients with newly diagnosed glioblastoma, randomized to chemoradiation plus bevacizumab or placebo. Co-primary endpoints were PFS and overall survival.
When the trial ended, the bevacizumab group had a median PFS of 10.6 months versus 6.2 months for placebo (P<0.001). The composite endpoint of PFS and death also favored bevacizumab (8.4 versus 4.3 months, P<0.001).
The advantage was observed across all prespecified subgroups, including patients with methylated or unmethylated tumors, Olivier Chinot, MD, of Aix-Marseilles University in France, and co-authors reported.
After a median follow-up of about 14 months, overall survival was 16.8 months with bevacizumab and 16.7 months with placebo. Deterioration-free survival was 9.0 months for the bevacizumab group and 5.5 months for the placebo group (P<0.001). Overall survival did not differ based on treatment assignment for methylated versus unmethylated tumors.
"In our study, treatment during progression-free time was associated with a consistently stable quality of life across all domains, sustained functional independence, and a diminished glucocorticoid requirement," Chinot and colleagues said of their findings.
"Considering the high baseline quality-of-life scores in this population of patients with newly diagnosed glioblastoma, maintenance of quality of life is a relevant treatment goal."
Gilbert and co-authors reported final findings from RTOG-0825, which involved 637 patients with newly diagnosed glioblastoma randomized to chemoradiation with bevacizumab or placebo. Like the international trial, RTOG-0825 had co-primary endpoints of PFS and overall survival.
After a median follow-up of 20.5 months, data analysis showed a median overall survival of 15.7 months in the bevacizumab arm and 16.1 months in the placebo group. Median PFS was 10.7 months with bevacizumab and 7.3 months with placebo, a difference that did not achieve statistical significance.
Methylation status was prognostic irrespective of treatment assignment, as overall survival was 23.2 months for patients with methylated tumors and 14.3 months for those with unmethylated tumors. Median PFS was 14.1 months and 8.2 months, respectively, for methylated and unmethylated tumors.
Patients in the bevacizumab arm had higher rates of neurocognitive decline, greater symptom severity, and greater decline in quality of life, as compared with the placebo group.
The author of an accompanying editorial offered possible explanations for the disconnect between PFS and overall survival.
"The most obvious explanation is that nearly half the patients in the placebo group received bevacizumab at the time of recurrence, potentially diluting a bevacizumab-mediated survival advantage, owing to patient crossover," said Howard A. Fine, MD, of NYU Langone Medical Center in New York City.
"Conversely, it is plausible that bevacizumab had little effect on true tumor progression but rather merely appeared to prolong progression-free survival when that outcome was assessed with the use of MRI, because of the ability of bevacizumab to decrease tumor blood-vessel permeability."
Consistent with the latter explanation, earlier trials of temozolomide demonstrated overall survival similar to that observed in bevacizumab-treated patients, he noted.
The discrepancy in quality-of-life data from the two trials "is neither trivial nor academic," Fine continued. If bevacizumab is associated with improvement in quality of life and performance status, those endpoints can form the basis of an argument in favor of bevacizumab regardless of its effect on survival.
On the other hand, if bevacizumab accelerates neurocognitive decline in patients with glioblastoma, its use in first-line therapy should not be advocated, given the questionable survival effects.
"It is worth noting that despite its limitations, bevacizumab remains the single most important therapeutic agent for glioblastoma since temozolomide," Fine concluded. "Ongoing and future trials will better define how and when it should be used in this population of patients, for whom so few treatment options currently exist."
The international trial was supported by F. Hoffmann La Roche, and investigators included employees of the sponsor. The RTOG trial was supported by the National Cancer Institute.
Chinot disclosed relevant relationships with F. Hoffmann-La Roche, Merck Sharp & Dohme, AstraZeneca, as well as a patent interest. One or more co-investigators in the international trial disclosed relevant relationships with F. Hoffmann-La Roche, Oligovax, Genentech, Merck Serono, Celgene, Tocagen, Apogenics, NewGen, Nobelpharma, Chugai, Eisai, Apogenix, Boehringer Ingelheim, Eli Lilly, and Merck Sharp & Dohme.
Gilbert disclosed relevant relationships with GlaxoSmithKline, Merck, EMD Serono, Abbott, Bristol-Myers Squibb, Novartis, Hoffmann-La Roche, and Genentech. One or more co-investigators disclosed relevant relationships with Merck, Genentech, Castle Biosciences, Pharmacyclics, Bristol-Myers Squibb, Abbott, Elekta, Novelos, Novocure, Vertex, Viewray, Institute for Medical Education, Demos, Elsevier, Colby, Stemina, Procertus, Accuray, NeuralStern, Pharemaco-kinesis, and NxPharmingen, as well as patent interests.
Fine disclosed no relevant relationships.
Primary source: New England Journal of Medicine
Source reference: Chinot OL, et al "Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma" N Engl J Med 2014; 370: 709-722.
Additional source: New England Journal of Medicine
Source reference:Gilbert MR, et al "A randomized trial of bevacizumab for newly diagnosed glioblastoma" N Engl J Med 2014; 370: 677-708.
Additional source: New England Journal of Medicine
Source reference:Fine HA "Bevacizumab in glioblastoma -- still much to learn" N Engl J Med 2014; 370: 764-765.
http://www.medpagetoday.com/HematologyOncology/BrainCancer/44383?xid=nl_mpt_DHE_2014-02-20&utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&eun=g726137d0r&userid=726137&email=egdo@optonline.net&mu_id=5894629
Hi all, been following this board for months(switched from Yahoo after the Fox videos came out) but first time posting since it took me time to get a reasonable # of shares and did not feel putting up my 2 cents was warranted w/o shares. Pasted this from medpage regarding standard of care for GBM and may have some interest; it summarizes a study that was in the New England J. of Med. I’m a little behind in checking the board so pardon me if this is already posted.
No Survival Benefit for Avastin in Glioblastoma Published: Feb 19, 2014 By Charles Bankhead, Staff Writer, MedPage Today
First-line therapy for glioblastoma remained unchanged after two randomized trials showed no advantage to adding bevacizumab (Avastin) to the mix.
A multicenter international trial showed a statistically significant 4-month improvement in progression-free survival (PFS) but no difference in the co-primary endpoint of overall survival among patients treated with radiation therapy, temozolomide (Temodar), and either bevacizumab or placebo.
A larger trial with a similar design also found that the addition of bevacizumab was associated with a numerical improvement in PFS but not overall survival, as previously reported. The trials were published simultaneously in the New England Journal of Medicine.
The results add to those of previous trials that "have not been very revealing" in terms of bevacizumab's effect on overall survival in newly diagnosed glioblastoma. How the results influence future investigation of the drug in glioblastoma remains to be seen, said Mark R. Gilbert, MD, principal investigator of the larger trial.
"Currently, we have no data to support use in front-line therapy," Gilbert, of the University of Texas MD Anderson Cancer Center in Houston, told MedPage Today. "In the recurrent situation, patient characteristics are very different. Patients typically have large, fairly rapidly growing tumors. The patient populations tested in these studies were predominantly patients who had extensive tumor resection.
"Bevacizumab may be better in patients who have large, bulky tumors as opposed to trying to prevent regrowth of tumors that have been extensively removed."
Investigators in the international trial noted that the bevacizumab arm maintained baseline performance status for a longer period of time, although the targeted agent was associated with more adverse events, including grade =3 adverse events.
Standard of care for newly diagnosed glioblastoma consists of chemoradiation with temozolomide, followed by temozolomide maintenance. Bevacizumab has FDA approval as second-line therapy.
Several phase II trials suggested a survival benefit with the addition of the angiogenesis inhibitor to standard first-line therapy, leading to separate randomized clinical trials, one involving investigators at 120 sites in 23 countries and the other based in the U.S. and coordinated by the Radiation Therapy Oncology Group (RTOG).
The international trial involved 458 patients with newly diagnosed glioblastoma, randomized to chemoradiation plus bevacizumab or placebo. Co-primary endpoints were PFS and overall survival.
When the trial ended, the bevacizumab group had a median PFS of 10.6 months versus 6.2 months for placebo (P<0.001). The composite endpoint of PFS and death also favored bevacizumab (8.4 versus 4.3 months, P<0.001).
The advantage was observed across all prespecified subgroups, including patients with methylated or unmethylated tumors, Olivier Chinot, MD, of Aix-Marseilles University in France, and co-authors reported.
After a median follow-up of about 14 months, overall survival was 16.8 months with bevacizumab and 16.7 months with placebo. Deterioration-free survival was 9.0 months for the bevacizumab group and 5.5 months for the placebo group (P<0.001). Overall survival did not differ based on treatment assignment for methylated versus unmethylated tumors.
"In our study, treatment during progression-free time was associated with a consistently stable quality of life across all domains, sustained functional independence, and a diminished glucocorticoid requirement," Chinot and colleagues said of their findings.
"Considering the high baseline quality-of-life scores in this population of patients with newly diagnosed glioblastoma, maintenance of quality of life is a relevant treatment goal."
Gilbert and co-authors reported final findings from RTOG-0825, which involved 637 patients with newly diagnosed glioblastoma randomized to chemoradiation with bevacizumab or placebo. Like the international trial, RTOG-0825 had co-primary endpoints of PFS and overall survival.
After a median follow-up of 20.5 months, data analysis showed a median overall survival of 15.7 months in the bevacizumab arm and 16.1 months in the placebo group. Median PFS was 10.7 months with bevacizumab and 7.3 months with placebo, a difference that did not achieve statistical significance.
Methylation status was prognostic irrespective of treatment assignment, as overall survival was 23.2 months for patients with methylated tumors and 14.3 months for those with unmethylated tumors. Median PFS was 14.1 months and 8.2 months, respectively, for methylated and unmethylated tumors.
Patients in the bevacizumab arm had higher rates of neurocognitive decline, greater symptom severity, and greater decline in quality of life, as compared with the placebo group.
The author of an accompanying editorial offered possible explanations for the disconnect between PFS and overall survival.
"The most obvious explanation is that nearly half the patients in the placebo group received bevacizumab at the time of recurrence, potentially diluting a bevacizumab-mediated survival advantage, owing to patient crossover," said Howard A. Fine, MD, of NYU Langone Medical Center in New York City.
"Conversely, it is plausible that bevacizumab had little effect on true tumor progression but rather merely appeared to prolong progression-free survival when that outcome was assessed with the use of MRI, because of the ability of bevacizumab to decrease tumor blood-vessel permeability."
Consistent with the latter explanation, earlier trials of temozolomide demonstrated overall survival similar to that observed in bevacizumab-treated patients, he noted.
The discrepancy in quality-of-life data from the two trials "is neither trivial nor academic," Fine continued. If bevacizumab is associated with improvement in quality of life and performance status, those endpoints can form the basis of an argument in favor of bevacizumab regardless of its effect on survival.
On the other hand, if bevacizumab accelerates neurocognitive decline in patients with glioblastoma, its use in first-line therapy should not be advocated, given the questionable survival effects.
"It is worth noting that despite its limitations, bevacizumab remains the single most important therapeutic agent for glioblastoma since temozolomide," Fine concluded. "Ongoing and future trials will better define how and when it should be used in this population of patients, for whom so few treatment options currently exist."
The international trial was supported by F. Hoffmann La Roche, and investigators included employees of the sponsor. The RTOG trial was supported by the National Cancer Institute.
Chinot disclosed relevant relationships with F. Hoffmann-La Roche, Merck Sharp & Dohme, AstraZeneca, as well as a patent interest. One or more co-investigators in the international trial disclosed relevant relationships with F. Hoffmann-La Roche, Oligovax, Genentech, Merck Serono, Celgene, Tocagen, Apogenics, NewGen, Nobelpharma, Chugai, Eisai, Apogenix, Boehringer Ingelheim, Eli Lilly, and Merck Sharp & Dohme.
Gilbert disclosed relevant relationships with GlaxoSmithKline, Merck, EMD Serono, Abbott, Bristol-Myers Squibb, Novartis, Hoffmann-La Roche, and Genentech. One or more co-investigators disclosed relevant relationships with Merck, Genentech, Castle Biosciences, Pharmacyclics, Bristol-Myers Squibb, Abbott, Elekta, Novelos, Novocure, Vertex, Viewray, Institute for Medical Education, Demos, Elsevier, Colby, Stemina, Procertus, Accuray, NeuralStern, Pharemaco-kinesis, and NxPharmingen, as well as patent interests.
Fine disclosed no relevant relationships.
Primary source: New England Journal of Medicine
Source reference: Chinot OL, et al "Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma" N Engl J Med 2014; 370: 709-722.
Additional source: New England Journal of Medicine
Source reference:Gilbert MR, et al "A randomized trial of bevacizumab for newly diagnosed glioblastoma" N Engl J Med 2014; 370: 677-708.
Additional source: New England Journal of Medicine
Source reference:Fine HA "Bevacizumab in glioblastoma -- still much to learn" N Engl J Med 2014; 370: 764-765.
http://www.medpagetoday.com/HematologyOncology/BrainCancer/44383?xid=nl_mpt_DHE_2014-02-20&utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&eun=g726137d0r&userid=726137&email=egdo@optonline.net&mu_id=5894629