Dr. West -

Thank you so much. I’ve shared this information/link with my oncologist. Am hoping to pursue some testing of my biopsy sample if there is tissue remaining, and if appropriate.

- Catharine

Catharine

Dr. West, I will get a blog up about this in the next couple of days and provide a link to the podcast. Again, thanks so much (and go Andy!) Linnea

Linnea

I found this a very informative talk. The question and answer part also was very informative, and it didn’t matter that I was not there live. It feels like I am in the clinic learning what’s going on. I liked learning about the ALK mutation and how the test is done, and the details around accuracy. I am excited to learn about the Lung Cancer Mutation Consortium, and I plan to read more about it and follow it’s progress. I will probably re-play this or read the transcript, as I couldn’t get all the details the first time.

After a lot of patience and nudging, I have moved forward on this. My interest started last June in 2009, now nine months ago. I have had a new biopsy and I am waiting for results of genetic tests for EGFR and K-RAS. If they are both negative, I am told, the test will be done for ALK. Naturally I don’t want to pin my hopes on any outcome. I am very grateful that Dr. West, Dr. Camidge, Dr.Pinder, and colleagues, have faith in the power of knowledge for patients.

Five years ago - repeat, five years - I was a stage-IV patient who had a wonderful response to a new treatment, went off pain meds, and could breath again. That drug was Pemetrexed (Alimta).

dfourer

Dfourer -

That is such encouraging news about your treatment! I hope your new biopsy test results contribute to your continuing success.

- Catharine

Catharine

Just double-checking since my oncologist is out of town, and I may have been the first person tested for ALK mutation at UPMC. My sample came back with 4.8% of cells showing transmutation by FISH. This was judged to be negative, as less than 15% is negative (according to path report and PA in my oncologist’s office). Given the newness of all of this at UPMC, I just wanted to double-check and make sure that’s the understanding of docs here (since Dr. Camidge indicated that the real danger of local testing was false negatives). Thanks!–Neil

neilb

That’s my understanding as well. The folks at Pfizer were telling me that they may at some later point turn to testing how people with lower levels on testing do with PF-1066, but right now they’re concentrating on patients with positive defined as the 15% threshold, as I understand.

Dr West

Re: Podcast, Drs. West and Camidge

If it was known in 2004 that the people who were most responsive to Tarceva were those with the EGFR mutation (test available since 2008), and in 2008-9 that Tarceva was a better first-line treatment for those people, why are people with that mutation still being given standard chemotherapy as a first-line intervention? I had a biopsy which provided tissue to determine I had adenocarcinoma of the left upper lobe of my lung and mediastinal lymph nodes, but no one mentioned to me that that tissue could be tested for EGFR and that testing might provide me with a better treatment than the standard chemo/RT (cisplatin + etoposide) that I suffered through last August (’09) and that had zero impact on my tumor. And this was at a major academic institution. I asked for another opinion on second-line treatments from a different oncologist (same institution) and he said since we had my tissue available already, he would just have it sent out to be tested for EGFR, and it showed the mutation on exon 19. I’m now on Tarceva (5 days so far). I know you don’t know why my first oncologist didn’t recommend EGFR testing of the biopsy, but why isn’t it routine to do so once you have the tissue? Is it a matter of cost? Of being up-to-date? Of believing the data? I’m very grateful for my second oncologist, but both are academic researchers as well as clinicians.

Shy One

There are a few issues. A big one is the time it takes to get test results. Many labs take 3-4 weeks to return a result once they have the tissue, and it can take weeks to get the tissue from the hospital to the lab. For many patients and many oncologists, a delay of 3-6 weeks before starting treatment is somewhere between inadvisable and ridiculous. Keep in mind that the IPASS trial didn’t enroll everyone, then order the test, then have everyone sit around for 4 weeks waiting for the test result before starting treatment. They ran tests after the fact on people who started treatment immediately. For all we know, the delay of starting treatment may be a bigger issue than the question of whether you get an EGFR inhibitor as first or second line treatment.

Another issue is that many, many, many people don’t have enough tissue available to run the test promptly. We need to get more tissue from a biopsy to ensure that enough tissue is going to be available to do these studies, but only about 1/3 of the patients on the IPASS study had tissue for testing. In just about every other study that does molecular testing after the fact, the rates of tumor tissue submission is 20-40%. Keep in mind, that this is from centers doing clinical research, and it’s exceptionally likely that treatment centers that aren’t doing clinical research are less likely to have tissue available for molecular marker work.

Cost is perhaps one factor: I just spoke with a patient today who received an “explanation of benefits” letter from her insurance company that says that she may be responsible for several thousand dollars for the cost of it; we should settle this, and in her case it was a pressing issue, but cost isn’t a negligible issue.

Finally, it’s worth noting that even though the IPASS results are very important and impressive, they actually DON’T show that people live longer if they start with IRESSA. Other studies show that people get a very comparable benefit whether they get drugs in the order A –> B –> C or in the B –> A –> C. Patients with an EGFR mutation may get their prolonged and dramatic response in starting in 2008, 2009, or 2010, but it appears that as long as you get it, you end up doing just as well. And by the same token, the side effects not experienced as a first therapy would very likely be the side effects experienced as a second line therapy: I know very few patients who don’t even bother doing chemo after they progress on an EGFR inhibitor. We can manipulate the story by highlighting the side effects and quality of life, but the evidence really shows that over time, if you end up giving people the same treatments, they end up with essentially the same survival and the same side effects, and all you change is the order.

In truth, there isn’t evidence that it’s critically important to give an EGFR inhibitor first, as long as patients with an EGFR mutation get it. Many oncologists may, in our frenzy to highlight the romantic ideal of molecular lmarkers, mistakenly mislead people into thinking that there actually is a survival benefit, but the evidence shows that the key is that you get it, not when you get it.

Dr West

Thanks very much for your reply. That was very useful and informative. By the way, I greatly appreciate your website. I have scoured it for much useful information on my adenocarcinoma and side effects, etc. This must take you an enormouse amount of time, and it’s a true mitzvah as far as I’m concerned.
I have another question, which may belong in a different forum. Have you seen people with adenocarcinoma of the lung who have also been diagnosed with thyroid cancer? I am in this situation (not yet diagnosed, but with a thyroid that is increasingly lighting up on subsequent PET/CTs). One dr. says get your lung cancer taken care of first because you probably won’t die its thyroid cancer, and another says get both looked at simultaneously.

Shy One

Lung cancer tends to have a much more pressing pace than thyroid cancer. I tend to focus on lung cancer with my patients and relegate thyroid nodules to a back burner issue, at least for locally advanced or metastatic lung cancer.

Dr West

Dr. West and/or other GRACE docs,

In the podcast Dr. Camidge’s opinion seemed to be that all adenocarcinomas should be tested for EGFR, KRAS (and ALK if the previous two are wildtype). Could you summarize when you think pts should get tested for molecular markers? Given that Tarceva is available as a second line treatment in advanced disease basically none of those pts in our clinic are being tested for EGFR, and I don’t think any of the adjuvant pts are being tested either, except through the RADIANT study (now closed - but even when it was open many pts were not eligible for it due to its stringent node sampling requirements). I would say that pts are being treated on a one-size-fits-all model if they are NSCLC non-squamous. What do you do in your practices and why?

rlei

I am heading to San Diego right now to give a talk tomorrow to an audience of oncologists about testing strategies, but that doesn’t mean that I have all of the answers (I don’t think anyone does).

I would have to say that it’s most appropriate to say that we don’t have enough evidence to make blanket statements that everyone should be tested for molecular markers, especially patients with squamous NSCLC. Right now, there isn’t any evidence even that patients with an EGFR mutation are worse off if they receive an EGFR inhibitor as a second line therapy instead of a first line treatment — progression-free survival in the first line is significantly longer if a patient gets what truly the “best” therapy for their disease, but overall survival appears to be comparable if every patient gets access at some point to the active drugs for them. In other words, there isn’t a clear penalty for a patient with an EGFR mutation getting their Tarceva in 2010 instead of 2009, as long as they are followed closely enough to intervene early in the course of progression. I also see many people misinterpret or over-interpret results of molecular testing, saying that patients who don’t have an EGFR mutation shouldn’t get an EGFR inhibitor, or patients with a KRAS mutation will get no benefit at all from an EGFR inhibitor (patients with a KRAS have very little chance of a significant “response” in terms of major shrinkage, but patients with KRAS mutations don’t seem to do worse than patients with just EGFR wild type and KRAS wild type in terms of survival with an EGFR TKI, and many can get a minor response or prolonged stable disease).

Though I greatly respect Dr. Camidge and many other leaders in lung cancer who are pretty emphatic about getting molecular diagnostics on just about everyone, I think that it’s a lot easier to be dogmatic if you are at a center that is doing much of this work in your own lab, or if it ties directly to your own research. For community-based oncologists, there are very real limitations, and I think that it’s desirable to have more information, but it’s not a clear mandate if patients are given access to the same drugs regardless of the outcome of the testing (e.g., patients can get Tarceva second or third line even if they haven’t been tested for EGFR mutation or are mutation negative) — and this includes patients with squamous NSCLC, who also appear to experience a survival benefit but very rarely a profound response from Tarceva (very much like patients with a KRAS mutation).

One exception that raises the value proposition for tissue testing is the ALK rearrangement and the opportunity for the minority of patients (about 4%) with an ALK rearrangement to receive the ALK inhibitor crizotinib (PF-02341066). Since that is not commercially available and is essentially only available to patients with tested and shown to have an ALK rearrangement, and because it can be so remarkably effective for the people with that molecular defect, I think it becomes very appealing to try to get molecular testing at least for the patients with a higher probability of having an ALK rearrangement (adenocarcinoma, minimal or no smoking history, younger). That will be a lot easier once the test is commercially available. In the meantime, I’m happy to have the Pfizer trials available at my center, so that I can test patients who are higher probability. But I think it’s a real challenge that the science has moved faster than the practical infrastructure to enable us to do this work.

We’re also running up against limits in tissue availability and the need to perform additional biopsies to do all of these studies. Patients may be quite varied in their acceptance vs. resistance of doing more invasive studies, and also of waiting on molecular tests before initiating treatments.

Dr West

Dr. West -

Good luck on your presentation. Your post of 3/26 comes at a handy time for me. Thank you. I am now in process to obtain molecular testing at Univ. of Colorado, provided there’s enough tissue remaining from my original biopsy from October 2008. Fingers crossed on that one as I don’t think a new biopsy is a good idea at the moment and I’m pretty sure my HMO wouldn’t go for it. I’ll be visiting HMO’s Pathology Dept. in the coming weeks to get more details and perhaps order the delivery of tissue to U of C.

I’ll be paying out-of-pocket. My HMO is not doing lung cancer molecular testing yet and I’m not sure I can wait until they start. I’m trying to decide whether to pursue just the ALK or to add in other tests (KRAS, EGFR, P53). Cost of ALK testing alone is not prohibitive, but the entire lung panel is more expensive. However, I want to maximize information from this testing round because there may not be enough tissue left for additional tests in the future.

I’m a good candidate for ALK (adenocarcinoma, never smoked, relatively young at 55). We tried Tarceva as first line treatment and while it shrank the main lung tumor, it worked for only a little while before mets showed up in bone and liver so I moved on to taxol/carboplatin/zometa. Six sessions of that combo led to further shrinkage and stability of the mets. Am now on Alimta and latest CT scan (3/18/10) shows stable disease, which gives me time to think about the molecular testing strategy.

Since this testing is all pretty new and moving at a remarkable rate, the HMO and oncologist don’t seem to have many guidelines or much advice yet, so I’m pretty much on my own. I’ll contact HMO’s clinical trials specialist this coming week to see if she can provide more details, so that might help. Your post gives me some additional information to consider.

Thank you.

- Catharine

Catharine

Catharine,

Congratulations on your good scan report! And good luck on your testing; hope they find something that can be a good option for you in the future.

Jim

JimC

Does anyone feel competent to update the Wikipedia article here:
http://en.wikipedia.org/wiki/Anaplastic_lymphoma_kinase
Wikipedia guidelines call for listing sources, and no “original research” or unsourced information.

Update: Some delays, but still waiting for my “ALK-Fusion” test results. Recently my tissue sent directly to Genzyme Genetics. This on advice from the Univ of Chicago trial site.
http://www.genzymegenetics.com
http://www.genzymegenetics.com/Our-Services/Oncology-Testing/alk-testing.aspx

dfourer

I was actually asked to give a talk to oncologists on this subject of what testing should be done on two occasions. The first was yesterday, and I’ve gotten some feedback and plan to make some changes before I give the talk again in a month at a different location (first in San Diego, next in Orlando). I think I may want to do a webinar to discuss this issue, perhaps to offer a counterpoint to Dr. Camidge, who I think is terrific, but I think there is room for a few different perspectives here. I’d also say that the field is evolving very, very rapidly, and that the infrastructure and policy (insurance coverage, etc.) are a few steps behind the science. I expect that my own views will evolve as new data come in, as is appropriate. My shortest answer is that ALK rearrangement testing is the most desirable, though EGFR mutation testing can be helpful. I actually don’t think EGFR mutation testing, though helpful, is critical if people are going to get an EGFR inhibitor anyway. And I’d really only be enthusiastic about ALK testing in someone with an adenocarcinoma, particularly one with a remote or no smoking history. Other tests are quite unvalidated and of no clear value. I would have no enthusiasm for paying for them or even using them to guide treatment if I had them available, frankly.

David, I’ll be very interested in the timing and whether you need to pay out of pocket for ALK testing. I’m relieved just to know that commercial testing is available somewhere. I had a patient last week in whom I recommended testing but wanted to check availability of commercial testing and couldn’t find any good answer from a Google search. My experience with Genzyme is that they can be slow and not especially customer-friendly, but I hope it works well for you and that commercial ALK rearrangement testing is feasible for the growing population of people who will want this.

Dr West

Jim - Thank you! Though “continued shrinkage” would be more cheer-worthy, I’ll celebrate”CT stable” any day.

Dr. West — You’ve provided more good information in your 3/28 post. I might opt for just the ALK test then. I keep saying “thank you” but that doesn’t seem like enough.

Just for information’s sake: The U. of Colorado ALK testing claims that turnaround time is one week. The ideal specimen should contain 100 tumor cells. A minimum of 50 tumor cells must be counted for ALK assessment. Here’s hoping my biopsy tissue can satisfy that requirement.

Catharine

Just a reminder that the Lung Cancer Mutation Consortium trial (LCMC) is free and they do everything by phone and fax. They are enrolling patients at the University of Colorado and test for ALK, Kras and several other different things. The turnaround seemed quick to me….maybe a couple of weeks. The coordinator is Kelly Lucas and I can hook anyone up with her email if you are interested.

Myrtle

myrtle

Myrtle -

Thank you! Turns out I was on the wrong path at U. of Colorado. Have now contacted Kelly and she is sending the LCMC materials my way. She’s pretty sure that I qualify and there is space left in the trial at Denver, so…

GRACE comes through again.

- Catharine

Catharine

UCLA is a part of the Lung Cancer Mutation Consortium and is about to start recruiting subjects. Edward Garon, MD, is the principal investigator on that study there. You can find contact information for him on the UCLA Medical Center web site (physician directory). His office is at UCLA’s facility in Santa Monica, CA. The U. of Colo. folks referred me to him when I called to volunteer and mentioned I was in southern California.

Shy One

Not to turn this into the Lung Cancer Mutation Consortium (LCMC) thread, but I received a follow-up contact from U of Colorado. In the follow-up email they apologized for misinforming me when I called their coordinator yesterday. Their procedures for enrolling patients in the LCMC study have changed. Since several LCMC sites are now up and running, U of Colorado can no longer consent patients who have not been seen in their clinic. As happened with Shy One, U of Colorado referred me to the contact person at UCLA. I called her and was told that UCLA is not up and running on their LCMC trial yet, but should be ready to start enrolling volunteers in about a month. The UCLA contact took my name and phone number so she can contact me when they start recruiting. Meanwhile, I plan to get more information from U of Colorado on participating there, if possible, even if it means a visit to Denver. Am trying to consider all options. Just glad to have the energy and resources to do so.

- Catharine

Catharine