Any update from Dr. Weiss' Clinical Trial on Acquired Resistance? - 1259947

Hi NJ, I'm sorry to have you wait so long for a reply. But I will ask Dr. Weiss to comment.
The talk on the whole not just this trial has been that there's no one way to treat focal acquired resistance.
But it sure does sound like the easiest way to handle focal progression.

Dr. Weiss would/do you use radiation on someone with just one progressing nodule, tarceva or no treatment, aka my husband's situation? If he were to progress, he's still NED.

Thanks,
Janine

NJ, We may have to wait on answers from Dr. Weiss. He's traveling to the World Lung Conference and may be out of range at least while he's traveling.

njliu: The trial is going slowly. I'm disappointed that we've only accrued three patients so far between UNC and Cleveland Clinic. However, we're about to get a lot of help from our friends. With the generous support of Astellas, the trial has also also opened @ ECU and the University of Pittsburgh and is in the process of also opening @ UColorado, UCSF, Swedish Cancer Center, Fox Chase, and Yale. With so many excellent partners across such a wide geographic spread, we hope to do better this year.

Janine: I'm not sure that I understand your question; if you can help me by clarifying a bit, I remain very happy to answer. I'm not sure how someone can have a nodule yet be NED or how someone progressing could be NED. The choice of what to do with a solitary progressing nodule depends on a bunch of other factors: it's location, it's size, the pace of its growth, and whether it's threatening anything (be it pain or organ/structure function). The situation that my trial addresses (solitary or small number of nodules in a patient otherwise responding to a targeted therapy) is the situation that I'm most enthusiastic about local ablation for (note the general response regarding "targeted therapy"; I think that the approach also deserves prospective study for crizotinib with alk and ros1). Observation can also be a powerful option for nodules that grow very slowly; it's great strength is the absence of potential for side effects or complications!

So sorry for being less than clear. I meant to ask a hypothetical question; if my husband recurs... My husband is NED and hasn't had treatment in over a year and that's the way I plan to keep it. But of course I worry about what we will do if he has progression. From reading Dr. West's post on his acquired resistance algorithm and my 4 years of reading Grace I understand that one treats focal recurrences on an individual basis.

Dr. West's says this, "Final bonus: this algorithm is also pretty close to how I’d approach someone with slow progression on nearly any other systemic therapy for other cancers. The key is the clinical significance, the pace of progression, and whether it’s very limited or diffuse.", http://cancergrace.org/lung/2013/01/23/acquired-resistance-algorithm/

So I ask you, might radiation be a consideration for you in someone with similar history as my husband who then recurred in a place or two?

NJ, did not mean to high jack your thread, but so glad to find there are more centers opening to the trail.

This is the first time I've read about your trial, Dr. Weiss, and it is very interesting. Am I correct in assuming that I would be considered someone with oligometastatic disease? I had one tumor 4 years ago (approx. 1 cm), removed thru lobectomy with no further treatment, then 3 years later had a single brain met (size of golf ball), with all NED scans in between. The brain met was discovered thru severe headaches as I had never had a brain scan. I have been on Tarceva for 13 months. Every scan I have ever had shows NED.

The question that confuses me is this - if Tarceva is targeting the EGFR positive cells, what exactly is it targeting in me if I show NED and both tumors were resected? I have never had a positive lymph node so I assume my progression was thru my blood stream.

If I would show progression, am I a person that you would be looking for in your study?

We sometimes see a cancer mutate and develop new characteristics, including potentially changing behavior and becoming more aggressive. But that's just a random event that I don't think can be predicted by anything other than doing well for a very long time, which means a lot of time for a potential random event.

-Dr. West

catdander: Hopefully, your husband won't need any therapy soon! He wouldn't be eligible for my trial b/c of the gemzar in between, but if he progressed in just a spot or two, and they were small, you'd consider that approach as a viable option outside of the study.

Sherry: Oligometastatic and oligoprogressive are different. "Oligo" implies one or just a few while the tail "metastatic" speaks to the # of spots with cancer while the tail "progressive" speaks to the # of spots that are growing. My ongoing trial addresses a narrow population: people who get a TKI (iressa, erlotinib, afatinib) as their first therapy for EGFR-mutated NSCLC who then progress in one or several spots. Dr Pinder's post that I cited in my article addresses oligometastatic cancer: the question of whether focal radiation might improve treatment outcomes for people with only a few spots total. I am working hard on getting a study going for people with oligometastic cancer either at original presentation, or after recurrence from a failed attempt at cure; right now, the concept is relatively well formed, but I don't yet have funding. To answer your question about what tarceva is targeting, we need need another compound word--"micrometastatic." If you had no cancer cells in you, tarceva couldn't help (nothing for it to hit and no need to). The idea of doing it is that there could be (or, to be more honest, likely are) clusters of cells in you too tiny to see; you're trying to keep them microscopic with tarceva. Our best CTs or PET/CTs can see lesions about 1/2 cm, while the tip of a pen is the size of roughly 10,000,000,000 cancer cells.

njliu: There is no theoretical reason to expect that effective treatment should encourage disease flair. The only way that I could imagine it doing so is by keeping the patient alive long (and thus allowing the tumor more total time to mutate)

I would say that we really can't know this. All we can do is speculate about theory and observe what happens clinically. I don't think we've seen any patterns to suggest what you describe.

-Dr. West

Dr. Weiss,

Thank you for your detailed explanation. Just so I understand what you are saying, when you say, "My ongoing trial addresses a narrow population: people who get a TKI (iressa, erlotinib, afatinib) as their first therapy for EGFR-mutated NSCLC who then progress in one or several spots." does first line therapy include surgery or is first line a chemo or medication that you take? In the last 4 years, I have had 2 resections but have only been on Tarceva, with no other treatments. Thank you!

It means first line systemic therapy of EGFR inhibitor, not prior chemo, and not something like surgery or radiation, which are not counted as a line of therapy.

-Dr. West

Thank you Dr. West. So apparently I do fit into that narrow population described, although I haven't had progression since starting Tarceva. When I do, this is certainly something to keep in mind.

I'm so glad this research is being done and other sites are being added. I guess the added funding by Astellas will make the adequate numbers possible. My pet peeve/jealousy about all the pink fund raising for breast cancer kicks in when I see Dr. Weiss and the rest of our lung cancer researchers struggle to get their trials off the ground. I wish the pink would share their good fortune.

NJ, I'm not reading your question the same way. It seems you're saying, in the case of oligomets, while there's only a couple of masses showing on the scan there is likely other, micro-metastatic masses forming. The micro mets will soon grow large enough to see and become a problem and there's only so much radiation that can be administered. If that's what you're saying then yes that's how stage IV nsclc is more likely to progress than just one or two masses. Dr. Weiss states this, "There’s actually a number of trials that have tried to cure patients with cancer spread to only a few sites (oligometastatic spread). This is a controversial subject..." in the post, Radiation to Address Cells with Resistance to Targeted Therapies
under the topic "Why Radiation for oligometastatic spread?"
Dr Pinder addressed this previously, "The argument is that metastatic cancer is a systemic disease: if we can see 2 metastases, there are probably hundreds of micrometastases that we cannot see on scans. If we use local therapy, it’s like playing whack-a-mole: as soon as one metastasis is destroyed, another will pop up and so on and so on…For this reason, we generally use radiation only with palliative intent in patients with metastatic cancers."

As more people live longer with stage IV nsclc the opportunities are there to find those who will live longer and better lives with focal treatments like radiation.

So, I know we will all benefit from the findings and TY Dr. Weiss

Janine

I don't normally speak for the doctors but I feel confident saying that Dr. West misunderstood what you were asking. He's the doctor who amassed this lot of specialists on our faculty hear at Grace and he and the rest will agree that the now infamous "whack a mole" analogy fits most people with stage IV nsclc.

This FAQ is an explanation of just that, http://cancergrace.org/cancer-101/2011/01/01/cancer-101-faq-i-have-meta…

The novelty of treating focal progression comes with the idea that some people won't progress as fast as others, the outliers. In Dr. Weiss' trial he contends that people with EGFR mutation who progress focally on tarceva will continue to do well on tarceva even after they receive radiation for one or two spots.

Other outliers are people the slow growing (indolent) nsclc like some BAC nsclc. My husband is also an uncommon example of experiencing very indolent squamous nsclc. Both of these cases may also be candidates for local treatment as explained here, http://cancergrace.org/lung/2013/01/20/mf-bac-algorithm/

If you read through Dr. Weiss' article closely you'll find the info as well.

It would be wonderful to grow into something as wildly successful at raising money as to be able to give enough money to a clinical researcher to make a dent in funding research. For now though I think reaching more people with the intent to educate is Grace's mission. Of course don't forget the donate link ;) http://cancergrace.org/donate

I hope this helps,
Janine