Erbitix vs Avastin

[shade]

I posted a few weeks back and got a wealth of helpful advice and support. My recovery from LAR on June 10 is progressing well enough for chemo to start the week after next. Prior to surgery we planned on 6 mos of FOLFOX. With the liver met they found and removed during surgery, my onc proposes to add Erbitux. He described the skin rash that Erbitux can cause. I asked if Erbitux is going to deliver a better result than Avastin. He explained the different ways these meds operate, and said both are good options. He cited 2013 report that showed Erbitux on average added 4 mos over Avastin. He is leaving it up to me, but he leans toward Erbitux.

Obviously I am concerned about the rash. Even the picture on Erbitux's own website is enough to give me pause. I know there are meds that can help manage the rash, but no magic bullet. The evidence for the superiority of Erbitux seems somewhat limited. The way I see it, I have reason to hope a cure, and I am guardedly hopeful, but I also know there's a very good chance my remaining years are limited. Do I want to spend a substantial chunk of my remaining life with acne? I know it sounds like a small or superficial thing but the fact is my mood and self image are poor right now anyway.

Any thoughts on the side effects of Erbutix, or on the Avastin vs Erbitux choice? I know many of you have been on one of these meds or the other, and some have taken both. Some of you probably have found yourself in the position I'm in. Any input is appreciated.

[BrownBagger]

I've been on Erbitux for about two years and while I had the rash at first, it eventually went away and I haven't been bothered by it for more than a year. I get out in the sun a lot, with no real problems. My face turns redder than normal at first, but then it just turns to a tan. While I had the rash, I took antibiotics, which helped suppress it, but also screwed my digestive system up, so I stopped taking them. I also got some cream and some gel from my onc, and they seemed to help. But like I said, it went away after awhile (maybe 6 months of steady decline in severity).

One problem that does persist, however, is sensitivity to dry conditions and cold. In the winter (and it was a really cold, long winter here in New York State), I have to keep my face lubed up with lotion to keep chapping to a minimum. It's not a problem in the summer, however, when the air is a lot more moist.

I've never taken Avastin, but Erbitux has been pretty good to me. Everybody is different, however.

[SkiFletch]

There's not a lot of data showing successful effects of Avastin taken in a post-surgical setting like yours. I do recall reading one study that it's wholly ineffective in preventing recurrence in stage III patients. In general, Avastin seems to better disrupt and shrink larger tumors as opposed to smaller or non-existent ones. Avastin's side effects can be significant too. Cardiac troubles, high blood pressure, and inability to heal from wounds are not trivial. If I were in your shoes, I'd probably not bother with the Avastin.

Erbitux I'm not terribly knowledgeable on apart from some of the things already mentioned here. I will offer one though though whenever anyone is in these questionable chemo situations. It's not like you're signing a legally binding contract to do this for 12 weeks... You can always try, figure out the side effects are worse than you care for and stop.

[BrownBagger]

My understanding is that Erbitux also carries some cardiac risk. That's why (I'm told), they always give it to you first, followed by your mainline chemo, which in my case is Irinotecan. They want to keep an eye on you for a couple hours post Erbitux infusion.

Funny thing about chemo. Before my last infusion (I always go alone), my wife said, "I hate chemo." I said, "You know, I'm a really good customer, I've been going there on and off for 5 years, and I have a lot of friends there, so I kind of look forward to it in a way." And, it's true. And, at least in terms of handling the juice pretty well, I'm one of their better patients. No drama.

[Val*pal]

I'm sure that everyone is different in his/her response to all the chemo agents. However, I know that my husband had terrible skin reactions to Erbitux, and after all that, it turns out that Erbitux was a fail for him. His skin reactions weren't just the acne usually described. He was on an antibiotic that seemed to keep that at bay (mostly), but his skin was so dry and itchy, he would scratch himself in his sleep and wake up with sores and welts that took forever to heal. His arms were a mess, to the point that he had to wear long-sleeved shirts. Erbitux also made him feel worse than ever, but he toughed it out until the first scan showed progression of the disease.

However, as someone suggested, it's not as if you have to continue with the Erbitux if you experience bad side effects. It is probably worth a try.

My husband had better results with Avastin, but it was no longer effective towards the end. Honestly, his prognosis was always very, very poor, so I don't think you should judge your decision by his results. I just know that at the time he took Erbitux, it totally kicked his butt - but he was already weakening from the progression of the disease at that point.

Good luck! You may have totally different results, and it's awesome that you have had such a long period of NED. Keep us informed!

Val

[pukalania]

Aloha Shade,
Have you done any genetic testing yet...there were a few recent studies showing Erbitux may not be as effective in patients who have certain gene mutations..

I'm sorry i'm not sure how to add the link to that post but if you search Erbitux wild type on this forum you may see a few things...i copied couple of links that were posted by radnyc

"It appears that adding cetuximab (erbitux) to chemotherapy in resectable kras wild type patients may not be a good mix.
Something to talk to your onc about if you're on this protocol."

http://meetinglibrary.asco.org/content/112298-132

http://www.eurekalert.org/pub_releases/ ... 040814.php

Also there was a study by MD Anderson (Scott Kopetz) regarding use of Zelboraf for patients who are EGFR mutated (not wild type thus Erbitux not effective), i'm sorry i don't have that link right now...but you can google it i'm sure...

As for the avastin, not sure how it works if there is actually no tumor...but regarding the post surgery risk...my husband started it 4 months after surgery, despite his current intestine leak..and knock on wood..is still taking it without further complications (5 months on it now with a tiny hole in his intestine, we were very worried about potential perforation and still are...but so far so good...i know that' s usually a big concern after surgery)

good luck!

[WifeOfMike]

Cetuximab (Erbitux) or Bevacizumab (Avastin) with combi chemo equivalent in KRAS wild-type MCRC
Date: June 28, 2014
Source:European Society for Medical Oncology
http://www.sciencedaily.com/releases/20 ... ceDaily%29

Summary: For patients with KRAS wild-type untreated colorectal cancer, adding cetuximab or bevacizumab to combination chemotherapy offers equivalent survival, researchers said.

"The CALGB/SWOG 80405 trial was designed and formulated in 2005, and the rationale was simple: we had new drugs --bevacizumab and cetuximab-- and the study was designed to determine if one was better than the other in first-line for patients with colon cancer," said lead study author Alan P. Venook, distinguished Professor of Medical Oncology and Translational Research at the University of California, San Francisco, USA. The CALGB/SWOG 80405 trial studied patients whose tumours were KRAS wild-type at codons 12 and 13. Patients received mFOLFOX6 or FOLFIRI at the discretion of their doctor and were randomised to cetuximab (578 patients) or bevacizumab (559 patients).

"There was no meaningful difference in outcome between treatment arms," said Venook. "In both arms patients lived close to 30 months. About 10% of patients lived more than 5 years. Overall patients did much better than anticipated and it was indifferent to the type of treatment." Because almost 75% of the patients received mFOLFOX6 as the chemotherapy, the interaction between the experimental drugs and chemotherapy will be limited, but an analysis is underway. The investigators are also conducting molecular analyses that may identify subsets of patients who did better or worse on either treatment.

Commenting on the data, ESMO spokesperson Dirk Arnold, Director of the Department of Medical Oncology, Tumour Biology Centre in Freiburg, Germany, said: "This was a long awaited phase III trial with a head-to-head comparison of two different molecular approaches: epidermal growth factor receptor (EGFR) blocking by cetuximab on one side and antiangiogenic (anti-vascular endothelial growth factor [VEGF]) inhibiting treatment with bevacizumab on the other side, both in combination with any standard first-line chemotherapy in metastatic colorectal cancer. The trial is important because the primary endpoint was overall survival. The FIRE-3 trial presented last year indicated that there may be an overall survival benefit with cetuximab but overall survival was only a secondary endpoint and data was inconclusive."

"Each of the monoclonal antibodies, in combination with standard chemotherapy, gave an overall survival of about 30 months: this is the longest overall survival in such a large trial and clearly sets the standard," Arnold continued. "We now know that using any monoclonal antibody with any standard chemotherapy in first-line treatment may give the patient the likelihood of surviving about 30 months. However there is no clear winner in terms of overall survival." "Next we have to see the analyses of the pan RAS cohort. Then we need to find out if different subgroups benefit more from anti-EGFR or anti-VEGF treatment. The type of chemotherapy or localisation of the tumour may also play a role."

In connection with this trial, results of the now updated phase III CRYSTAL trial and phase II OPUS trial show that adding cetuximab to FOLFIRI or FOLFOX4 in the first-line treatment of metastatic colorectal cancer provides a greater benefit for patients with RAS wild-type tumours compared with the initial analysis with KRAS wild-type selected patients. Patients with RAS tumour mutations did not benefit.
Commenting on the data, Dirk Arnold said: "The CRYSTAL and OPUS trials confirm the results of the PRIME trial of FOLFOX and panitumumab, another anti-EGFR. These trials excluded all mutations in the KRAS and NRAS genes and looked at the benefit of anti-EGFRs in wild-type patients. All three trials consistently show that anti-EGFRs plus chemotherapy do better than chemotherapy alone. And anti-EGFRs in pan wild-type patients do better than anti-EGFRs in only exon 2 wild-type patients."

He added: "The only issue raising some questions is the fact that patients who bear any mutations may be at risk of a detrimental effect. So genetic testing is not only a prerequisite to ensure the maximum benefit, it is also needed to ensure that we do not harm patients by treating them."

Just got this one yesterday, hope it is helpful
wife of Mike,
Vicki

[shade]

Thanks to all for the wealth of input. I will read and re-read it, and go back to my onc for discussion. There's so much to consider here.

Pukalania, my onc mentioned the genetic testing and will complete that before making the final decision. Thanks for pointing that out.

Again, thanks....

[SkiFletch]

Did that study above recruit folks at all stages of treatment? Pre-surgery, post surgery? If so, were the outcomes different depending on when it was given?

Edit: Found it. Looks like the patients were all pre-surgery. Which doesn't really apply for the OP's case as I alluded to above. Cool study either way.

[WifeOfMike]

Medscape Medical News from the 2014 Annual Meeting of the American Society of Clinical Oncology®
Medscape Oncology.........All-Out Assault on CRC
Louis M. Weiner, MD, Axel Grothey, MDDisclosures
June 09, 2014

Here is a relative highlight regarding Avastin/ Erbitux:
Colorectal Cancer: A Plenary Presence

Louis M. Weiner, MD: Hello. I am Dr. Louis Weiner, Director of the Lombardi Comprehensive Cancer Center and Chair of the Department of Oncology at Georgetown University in Washington, DC.

Welcome to this edition of Medscape Oncology Insights in Gastrointestinal Cancer. Today we will highlight some of the presentations from the 2014 annual meeting of the American Society of Clinical Oncology (ASCO®). Joining me today is Dr. Axel Grothey, Professor of Oncology at Mayo Clinic College of Medicine, in Rochester, Minnesota.

This year the plenary session featured a study in colorectal cancer presented by Alan Venook.[1] We have been waiting for these results for quite some time. What have we learned? Axel, would you like to summarize the results of that study for us?

Axel Grothey, MD: I am more than happy to. This study took 10 years to complete, and much has changed during that time. This study showed that we underappreciated where we would be in the treatment of colorectal cancer in 2014. The study integrated 2 drugs, which were new in 2004. Bevacizumab and cetuximab were approved within 2 weeks of each other in 2004. The question was, which of these drugs is the better first-line therapy added to chemotherapy?

The study allowed investigators to choose FOLFOX (5-FU, oxaliplatin, and leucovorin) or FOLFIRI (leucovorin, 5-FU, and irinotecan) as the chemotherapy backbone. More than 70% of the patients (1150) received FOLFOX chemotherapy in the United States and were randomly assigned -- eventually in the "14th amendment version" of the study because things change over 10 years -- to bevacizumab or cetuximab in first-line therapy. The primary endpoint was overall survival. There is good news and bad news. The median overall survival was 29 and 29.9 months in the FOLFOX and FOLFIRI groups, respectively. There was no real difference between the groups.

This was a patient population with KRAS wild-type tumors and KRAS exon-2 wild-type tumors. The importance of the study is that it takes a little bit of the wind out of the sails of the study that we saw last year (the FIRE-3 study),[2] which was a German/Austrian trial comparing cetuximab and bevacizumab added to FOLFIRI. That study did not show any difference in response rate or progression-free survival. However, that study also had an interesting and unexplained (until now) finding of a difference in overall survival in favor of cetuximab, which became even larger when the refined patient population underwent more RAS testing[3] to eliminate patients with NRAS and KRAS mutations.

Here is a link to Multidisciplinary Treatment Cancers of the Colon and Rectum
2014 Gastrointestinal Cancers Symposium

ALL ABSTRACTS............You will find the abstract showing the highlight above there
http://meetinglibrary.asco.org/abstract ... mposium/62

Wife of Mike,
Vicki

[shade]

Vicki,

Is this the presentation you are referring to? Thanks!

http://meetinglibrary.asco.org/content/126013-144

[shade]

This link seems to be describing the same study, summarized in language I can comprehend. The study is designated as CALGB 80405, and the primary author is named Alan Venook. I think these results were presented at a plenary at the 2014 ASCO.

http://www.kantarhealth.com/blog/stepha ... c-patients

Anyone that thinks I am getting this wrong, please correct me. Best to all...

[WifeOfMike]

from a quick glance at how many were in the trial and the dates I believe so....

I actually went thru quite a lot of the 150 abstracts, looking at titles of interest then clicking thru to the abstracts.
There may have been another one or two on the subject, but it was during a couple of up till 2 AM crash course research projects, so I am a little fuzzy
I pull a lot of info, during those "sessions", and either save links or cut & pasted articles into word docs (then save under topic).
That way when a buddy (like you) needs something it is quite often at my fingertips

Hope it helps...... this study was done over an extended period of time. KRAS/BRAF/NRAS mutations (RAS Family) were unheard of as far as a determining factor on whether Erbitux worked- for non-wild (NO mutations) and those with mutations. Early work found KRAS relative, later work (clinical trials found all) the other BRAF/NRAS (RAS) mutations were also relative. It was announced in a major gathering of the minds meeting ASCO.

I have been saying this for awhile.... GET TESTED. Hubby was tested for KRAS, BRAF, NRAS, CMET, EGFR, MSI, P13K, TS, VEGFR2, ERCC1. back in July 2013 from original tumor slides. Now that he has been on 2 standard chemo cocktails, Stivarga, 1 clinical trial...... just signed up for another & on waiting list for yet another...... I know the last one is going to require a new tumor biopsy (of his lung, which is only place he has cancer). I plan on having a much broader testing done at the same time. I do know he may have changed (body gets more resistant to treatments taking its toll), so I want the tools these ONC's use to be the most updated info on my man as possible to guide them for best treatment in future. It may save him from unnecessarily going thru treatment they know will not work. Make sense?

Previous testing insurance did not pickup, so out of pocket was $200. I also know it saved a lot of down time in being included/ excluded from clinical trial NOW. So I am hoping wider testing will do even more in the future.... such as knowing PD-L1 status. Look at my recent posting: Online Database= Personalized Medicine. It will give you a BIG incite as to what all ONC's will be using as road maps to YOUR CARE in the future

BEST WISHES!!!
Wife of Mike,
Vicki

[ldomo]

I was on both. I never had a rash with the erbitix.

[WifeOfMike]

Here is an excerpt that is relative from the 2014 ASCO Meeting:
As part of our coverage of the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting, Cancer Network is speaking today with Leonard Saltz, MD, chief of the gastrointestinal oncology service at Memorial Sloan-Kettering Cancer Center, about some of the colorectal cancer research that is expected to be presented at the meeting. —Interviewed by Leah Lawrence

Cancer Network: Thank you for speaking with us today, Dr. Saltz. A late-breaking abstract will be presented in the plenary session discussing chemotherapy plus bevacizumab or cetuximab in patients with metastatic colorectal cancer without KRAS mutations. Can you discuss why the results of this abstract will be important?

Dr. Saltz: This is a study that has taken a very long time to complete. It has really been a mammoth effort. I think that we are going to be learning a tremendous amount about treating colon cancer from this study. The specific information is a comparison of treatment with a standard cytotoxic chemotherapy backbone—either FOLFOX or FOLFIRI, investigators and patients were given their choice about that—with patients then randomized to receive either bevacizumab or cetuximab. This has only KRAS wild-type patients included, and, based on the technology available at the time, it is those patients that are exon 2 KRAS analyzed. We now understand that non-exon 2 KRAS mutations and NRAS mutations would also be relative contraindications to inclusion of patients and treatment with anti-EGFR therapies such as cetuximab. A later analysis will look at that subpopulation. This is basically going to answer the question: Is there a superiority to treating KRAS wild-type patients with an EGFR inhibitor upfront vs using bevacizumab, a VEGF inhibitor?

The study is the culmination of more than a decade of effort and involved the cooperative groups working together to answer a question that would not have been addressed outside of the cooperative group network, and I think that is very important in its own right. The study originally was asking the question of whether the combination of using anti-VEGF and anti-EGFR therapy together would be a useful thing to do. We have already gotten the answer that that was an inferior arm that was closed early. Also, when we started the study we did not know about KRAS for selectively, so that was a modification made in the study, and the data presented here are only those patients since KRAS genotyping became available—and only those patients that are KRAS wild-type.

Cancer Network: During the oral abstract session, you will be the discussant for two abstracts dealing with maintenance therapy. Why is this an important topic in colorectal cancer right now? How will these abstracts add to the clinical knowledge related to this topic?

Dr. Saltz: This is an interesting dichotomy and style here, because I think these are more relevant to European investigators, or at least more interesting to European investigators than to American investigators. Not that that should be the case, but I think it is.

American investigators and American clinicians have tended to be resistant to the idea of treatment breaks and maintenance therapy, and tended to push treatments to their toxicity levels; whereas, Europeans have been more interested in either stopping chemotherapy after a fixed period of time or in cutting back the therapy to a so-called maintenance therapy. The data to support this approach was first published in the Journal of Clinical Oncology back in 2006 by Christophe Tournigand in the OPTIMOX study, which showed that in patients being treated with front-line FOLFOX, if one made a plan to stop the oxaliplatin after the first 6 cycles and just continue with the 5-FU and leucovorin, with the option to bring oxaliplatin back in at a later date, that patients had lower toxicity, certainly lower drug expense, and the same long-term outcome in terms of duration of disease control and in terms of overall survival. We have known for a long time that we can drop oxaliplatin out of the mix early and that we should.

In the CAIRO 3 study, the question being addressed is, Should we stop everything? Should we simply drop chemotherapy after 4 months and observe? The answer is that there does appear to be a benefit in terms of continuing at least maintenance chemotherapy. I don’t find that terribly surprising or earth shattering. To some degree, I find this a confirmation of some earlier studies that have been presented including the OPTIMOX 2 study. For anyone who was considering stopping therapy cold turkey this will provide some data justifying that continuation of fluoropyrimidines plus bevacizumab has some advantages over observation.

The other study that is being presented is a trial looking at taking patents with fluoropyrimidine, oxaliplatin, and bevacizumab, and after 6 months, if they still have good disease control, randomizing them to stop therapy, to continue with bevacizumab alone, or continue with fluoropyrimidine. What we see is in this study, which is 840 patients and is split between three arms, the overall survival did not appear to be meaningfully different. The data are preliminary for that. The duration of disease control is about 2.5 months longer when bevacizumab and fluoropyrimidine are continued. Single-agent bevacizumab looks to be inferior to bevacizumab and fluoropyrimidine. It is a month better in terms of duration of disease control than doing nothing. In this essentially open-label study with investigator adjudicated progression, I wouldn’t make anything of a 1-month difference in duration of disease control. I don’t think it gives any support to single-agent bevacizumab. I don’t think that has any role in treatment of metastatic colorectal cancer. It does suggest that continuation of cytotoxic chemotherapy at a maintenance level has some benefit. It would be nice if the study had included a chemotherapy-only arm without continuation of bevacizumab, but we don’t have those data, and I doubt that we ever will. We will just have to make use of the information available. I think these studies are of interest. I think they will convince believers and not sway a whole lot of conversions from one approach to another. They will make for some interesting discussion in terms of treatment options.

http://www.cancernetwork.com/asco-2014- ... c-research

wife of Mike,
Vicki