I am on my flight back from ASCO, the annual meeting of the American Society of Clinical Oncology in Orlando, where over 20,000 oncologists from around the world discuss the newest data in clinical and translational research. This year’s theme was personalized oncology care.
Last year we made a significant step forward in personalized oncology with the identification of a mutation in KRAS which is found in about 40 percent of colon cancers. This genetic switch predicts efficacy of drugs such as Erbitux and Vectibix. Since then the European Regulatory Agency EMEA approved KRAS testing in first-line metastatic colorectal cancer treatment, and since last Monday my colleagues in Europe including England can use Erbitux in wild-type KRAS tumors for first-line treatment t which we in the USA can not do.
The data have been submitted to FDA for review to be able to use Erbitux or Vectibix in first line treatment, and we expect a decision in the next couple of months.
More and more American physicians test for KRAS mutations, but still mainly when we consider starting Erbitux or Vectibix. Increasingly in the US we are beginning to test with the diagnosis of metastatic colon cancer because the planning of treatment strategies may significantly change.
This year’s meeting asked the question: Do we have new information on additional markers?
There was promising data on PI3K mutations and BRAF mutations as well as on PTEN loss and expression of the EGFR ligands. It seems that PI3K and BRAF mutations may be not so clear as the KRAS mutation story. Studies presented at ASCO showed that the data are not consistent indicating that testing for these markers should not be done routinely yet.
PTEN loss is complicated and not easily clinically feasible since you need tissue from the metastatic site and no one likes to biopsy liver or lung lesions for a molecular test. The concordance of PTEN loss is not great when compared between primary and metastic site. This is because the method of PTEN inactivation is not a mutation but methylation which is dependent on the tumor’s environment which obviously is different in the primary tumor and liver or lungs mets.
The most promising is the EGFR ligand expression. Additional data suggested that high levels increase the probability of response to EGFR inhibitors. The problem is methodology and how to determine the cut off level. In other words, what is high and what is low.
June 04, 2009 at 8:44 am, j.d. said:
I am a stage 4 colon cancer patient with wild-type KRAS living in the U.S. I was diagnosed in August 2008; my oncologist put me on Erbitux as first-line treatment instead of Avastin because we wanted to avoid the 6-week delay before liver surgery. The insurance company accepted everything without any trouble. I had the surgery and am now on Erbitux as part of adjuvant therapy. I was not part of a clinical trial or anything – surely this treatment plan was FDA approved?
June 04, 2009 at 9:45 am, Heinz-Josef Lenz said:
you are lucky you got the erbitux because the combination with chemo seeem to be the most effective therapies prior to surgery. HJL
June 05, 2009 at 2:19 am, Maritza Zeljak said:
My mother started chemo 4 weeks ago along with erbitux. Her apetite and diarrea are getting worse and I read your report on ginger. I gave her ginger tea but it seems not to do much. Are the pills better and how much will be good to hopefully see some relief?
June 05, 2009 at 9:40 am, Heinz-Josef Lenz said:
not easy to answer some say the pills or the chewinggum work the best for them……if ginger does not work you should add prescription drugs such as reglan or zofran. please discuss with your oncologists. HJL
June 12, 2009 at 12:42 pm, MF said:
I am stage 4 colorectal cancer pt. In 2007 diagnosed then colon rescetion with 7 cycles of folofx/avastin afterwards.In 2008 had a liver resection and 6 more cycles of folfox/avstin.in 2009 I had RFA for a new liver tumor. Is there any hope for me?
June 12, 2009 at 12:58 pm, Heinz-Josef Lenz said:
YES no doubt liver limited disease gives us the chance to do curative surgeries it seems the surgery was successfully removing hte liver lesions followed by RFA……..we have many patients we had to resect more than 3 times to get them cancer free. as you know no garantee but certainly the chance. you also should discuss options such as therasphere with your oncologists. a liver directed therapy. HJL
July 07, 2009 at 4:18 pm, MF said:
Dr.Lenz, recently I read about ALVAC-CEA/B7.1,colorectal cancer vaccine at USC. My oncologist doesn’t want to give me more chemo for the fear of damaging my liver.So far had a liver resection of one ( 1cm tumor) Mar 2008 and RFA of (2cm tumor) June 2009. In March 2009 also they removed a 2×3 cm adenoma polyp from colon near previous resection. By reading about the vaccine could not tell whether this is beneficial for some one in my situation.Appriciate your answer.
July 07, 2009 at 4:23 pm, Heinz-Josef Lenz said:
unfortunately the vaccine trial is closed. there was some activity but not as much we hoped for, Sanofi closed the development. very difficult to judge in your case whether further chemo or what chemo makes sense just dont have the details and info to make specific treatment recommendations. you may want to discuss this with your oncologist including maintenance therapies such as xeloda/avastin which is less liver toxic. HJL
July 20, 2009 at 4:58 pm, Zaklina said:
My mother had xelox plus avastin first line, and then went for liver surgery to get rid of all metastatic disease. Unfortunately she has multiple new mets in both her lungs and liver. Her oncologist is recommending folfiri plus avastin. Is there a clinical trial that you would recommend?
July 20, 2009 at 10:50 pm, Heinz Josef Lenz said:
sorry to hear about the progression of the colon cancer in your mom. they are clinical trails available for patients who fail first line chemo, is she kras wt? depending where she lives she can ask what trials would be availalbe for her. FOLFIRI avastin is a good option wihtout a trial. hope this helps. HJL
July 21, 2009 at 8:13 pm, Zaklina said:
Dr. Lenz, Thank you for your response. Yes on KRAS. We live in San Diego and the clinical trial below looks promising. Please let me know your opinion on this.
http://health.ucsd.edu/cancer/clinicaltrials/results.htm?proto=6785
Thank you so much.
July 24, 2009 at 12:20 pm, MF said:
My oncologist has adopted the policy of wait and see, PET/CT scan every 3 months.He doesn’t believe in maintenance therapy.You have suggested maintenance therapy of Xeloda/avastin for me. Is there data to support this to beneficial. I would appreciate your opinion.Will you point me to where I can look for data.
MF
July 26, 2009 at 5:13 pm, Heinz-Josef Lenz said:
sorry was out ot town and could not respond earlier. there are no clear data about the maintenance therapy since to construct a trial is difficult. However we know that the risk of recurrence is 70-80% in the first two years and in high risk patients i consider to extend the adjuvant chemo with some maintenance explaining that we have no proof that it works. glad he is doing CT/PET every 3 months. HJL
August 15, 2009 at 5:33 pm, G. Pruzan said:
My husband had a large colon mass (splenic flexure?) found and operated on in August 2007. It was outside the colon wall and in 1 lymph node. At the end of June 2009 they found a 3cm lesion on his liver and two enlarged lymph nodes nearby. He’s gone on folfox plus avastan. He had 6 months of folfox after the initial surgery. So far he’s had two treatments. His kras testing just came back showing he’s got the wild type. Would you switch to erbitux instead of avastan at this point? The oncologist was planning on doing a CT after two months. A friend suggested a new study says get PET scans earlier. Any comments on this?
August 15, 2009 at 7:55 pm, Heinz-Josef Lenz said:
would monitor success the efficacy of folfox/avastin with CT scans every 6-8 weeks if any progression you should consider erbitux in combination with CPT-11. HJL
October 27, 2009 at 11:09 pm, Linda Stout said:
Dr. Lenz, as far as the KRAS mutation test. Is it possible to not have the mutation before erbitux and then develope the mutation later therefore making vectibix an ineffective choice? Do you recommend the test prior to both therapies?
I noticed you recommend the ResponseDX Colon test at responsegenetics.com . Is this still a beneficial test if I have already received all the standard therapies (5fu, Cpt-11, Leucovorin, oxaliplaten, avastin, erbitux, vectibix)?
Thank you (I am so glad to find your blog again)
October 27, 2009 at 11:59 pm, Heinz-Josef Lenz said:
not possible kras mutation develop before even cancerhas developed it is an early step in the development to cancer. If cetuximab does not work, there is no reason to use vectibix at all. responsegenetics is helpful to decide foir FOLFOX or FOLFIRI and erbitux or avastin.
October 28, 2009 at 11:35 am, Linda Stout said:
Dr. Lenz, Let me reword my question. Is it possible to develop the KRAS mutation during you chemo journey. I had erbitux last in October of 2008. It worked. Now one year later Oct.2009 would you suggest a patient be then tested for the KRAS mutation prior to receiving Vectibix?
Do you have any information on the test that is available to test tumor tissue for any other chemo choices that are likely to work? Like using a lung cancer drug to fight colon cancer for example.
Thank you