GRACE :: Lung Cancer


Dr West

Rising to the Challenge of Narrowed Patient Subgroups

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Only a few years ago, oncologists saw lung cancer as divisible into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with very little relevance to any division beyond that point. We knew that patients with NSCLC could be categorized into having adenocarcinoma (including the subset of that larger group, bronchioloalveolar carcinoma (BAC), squamous, large cell and large cell neuroendocrine carcinoma, and into those with and without a significant smoking history, and other demographic variables, but they weren’t a primary focus when we didn’t perceive that these differences had clinical significance in our treatment recommendations. And at that time, most people received remarkably similar treatments, with first line trials in advanced NSCLC incredibly commonly designed as carbo/Taxol (paclitaxel) +/- new drug, and second line trials of Taxotere (docetaxel) +/- new drug, or a direct comparison to placebo in previously treated patients.

Things have changed dramatically in the lung cancer field over the past few years, and in most ways definitely for the better. We now see more patients being cured with earlier stage disease and living years with advanced NSCLC, even if longer term results we might call cures remain elusive. Many of these improvements have come in the setting of a new era in which we categorize NSCLC patients by histology, sometimes smoking status and patient race, and increasingly by presence or absence of certain molecular features (we still aren’t sophisticated enough to have learned how to subcategorize groups within SCLC). We now have different treatment pathways for squamous vs. non-squamous NSCLC, Avastin (bevacizumab) eligible vs. ineligible (for a variety of reasons), and now pathways directed by the presence or absence of molecular markers like EGFR mutations, ALK rearrangements, and potentially K-RAS and other biomarkers like ERCC-1, RRM-1, etc. And by individualizing to deliver the best treatments for more narrowed populations, we’ve incrementally improved survival for many of these subsets.

But there’s been a challenging by-product of this process, which is that it’s becoming harder to do clinical trials in which the target population is much smaller than it used to be when drugs were invariably approved for all patients with advanced NSCLC. Pfizer’s trials with crizotinib need to screen thousands and thousands of patients to identify a few hundred with an ALK rearrangement. Meanwhile, progress on more limited groups of patients, such as those with BAC or large cell neuroendocrine carcinomas, are extremely understudied because it’s infeasible to reach such a limited population of patients who are geographically dispersed. We’re now identifying new molecularly defined small populations, such as those with a K-RAS mutation and those with an EGFR mutation who develop an acquired mutation after a great response.

Unfortunately, pharma/biotech companies can’t and won’t run trials for small target populations (markets) and that require a decade to enroll trials. And research centers can’t afford to run trials in which each center only sees 1-2 patients per year who would be eligible.

But the internet provides a remarkable way for people who are geographically dispersed and share an infrequent but common interest to connect with each other and work collaboratively. There may not be enough die-hard fans of Buffy the Vampire Slayer to have groups meet together in person, but there is a vibrant online community. More importantly, people with rarer medical issues can galvanize forces and help neutralize their decentralized status, sharing information and pooling their efforts to move research forward to help themselves.

GRACE member linda22 has BAC and is part of a self-aggregating group with BAC who have found each other online. They’re now working together to create banks of tissue of BAC tumors and, hopefully, to engage in clinical trials together. I think that if people with EGFR and KRAS mutations, ALK rearrangements, large cell neuroendocrine tumors, perhaps even squamous NSCLC patients, or any other clinically relevant subsets can find each other and become an easily identified group for clinical trials, investigators could better study these groups we’ve always regrettable said were “too rare to study”;pharmaceutical companies could take a chance on studying a drug in a clinical indication with far more confidence that they could complete these trials in a timely way. And patients and family members could play an active role in accelerating the rate of clinical progress in cancer, so that we no longer need to say that a cancer subgroup is too small to study.

I’m starting a new discussion forum thread in the lung cancer section on lung cancer subgroups (start a new group by clicking this link), hoping to facilitate that self-aggregation of people into groups that could facilitate more investigators investing effort and pharmaceutical companies investing money in new avenues of research. Patients could play a more active role than ever before in overcoming the bottlenecks that occur as we define more sub-specialized clinical populations.

17 Responses to Rising to the Challenge of Narrowed Patient Subgroups

  • JoeSperrazza says:

    What an incredibly powerful idea: “Web 2.0″-enabled medical research study cohorts. I’ve never heard of this before – is it absolutely unique, or has it been done with other diseases?

  • Laya D. says:

    Wonderful idea, Dr. West!!!!!!! (Applause…)

  • benMcBen says:

    Hi Dr West

    I think thats a very powerful idea – have you considered the “taxonomy” of how these groups are set up? I think it would also be a very powerful idea (though perhaps one for later) to push this out into social networking sites (via groups). To make this relevant I think we would need a taxonomy that allowed researchers to mine the data, without making it soooo complicated no one wopuld know what to do.

    cheers & ttfn benm

  • Dr West
    Dr West says:

    There are a few examples of this in other medical settings, but not enough. It’s a great way for patients to become much more integral as true partners with the medical community. And I truly believe this will go a long way to helping accelerate the pace of clinical research for smaller, defined populations that are geographically dispersed. Think of how much faster we can develop new agents if the right patients new where the trials for them were located, and the investigators and pharma companies knew that they could readily reach dozens of patients or more with an acquired resistance to an EGFR mutation, KRAS mutation.

  • Dr West
    Dr West says:


    I haven’t specifically thought about creating a taxonomy, though I suppose that within the range of categories, such as on the discussion forum here, there could be relevant categories by histology, molecular markers, etc., that people could join and that investigators and companies could specifically reach out to and partner with to efficiently run clinical trials.

  • icandoityesican says:

    Oh my gosh, but I have gooseflesh. Dr. West, I’m technically illiterate but most personally excited at the prospect of this proposal. How do we start??? And what can I do to get involved?

    The word GRACE in this site’s title is so apt.

  • Catharine says:

    This is a fantastic idea, Dr. West.
    What would an individual specifically need to know to accurately “plug in” to one of the subgroups?
    Thank you.
    – Catharine

  • Dr West
    Dr West says:

    I think the subgroups that make the most sense right now are the following:

    1) EGFR mutation/acquired resistance to EGFR inhibitor
    2) KRAS mutation
    3) ALK rearrangement
    4) Bronchioloalveolar carcinoma, and ideally even specifying whether mucinous or non-mucinous (if known)
    5) Large cell neuroendocrine carcinoma
    6) Squamous cell (a pretty large population, but perhaps if an investigator or company wanted to reach this population, they could plug into this group readily to complete a trial)
    7) never-smoker with neither EGFR mutation, KRAS mutation, nor ALK rearrangement

    Some of these populations don’t have treatments specifically targeting them yet, but someone might be able to do research more quickly on these populations if they knew where to find many readily.

    People can suggest other groups. I don’t think it’s necessary to have a group for adenocarcinoma or other very large groups, since investigators and companies don’t worry about not being able to find patients for such trials.

    I’ll start threads for each of these, and if someone wants to join a group. just add a comment to the thread. Feel free to also include your e-mail, though we could find it from your username. Please know that if you sign up, it would mean that people would potentially contact you outside of GRACE.

    If someone else wants to lead a group, just say so in the thread. GRACE doesn’t necessarily need to “own” these groups, but rather, we just want to ensure that the people who are trying to do research on patient subgroups can readily find suitable patients, and vice versa.

  • Dr West
    Dr West says:

    Here’s a link to the groups on the forum I’ve set up:

    If people want to join one, just add your username and any additional info as you see fit to the right thread to match the group for you.

    Anyone who can think of another group that is understudied but could potentially be the subject of more/better research if investigators could just find the right patients, feel free to start another thread in that section of the forum.

  • Laya D. says:

    Hi Dr. West,

    Is small cell lung cancer considered to be one of the “larger groups” for which investigators/companies can easily find patients (for trials)? If not, maybe we can add a subgroup link for this groups of patients.


  • JoeSperrazza says:

    I think this effort has great potential, and is worthy of making known more broadly to the cancer community.

    Have you given any thoughts to:
    * A press release
    * An announcement on other Cancer resource website

    – Joe S.

  • Dr West
    Dr West says:

    With regard to squamous cell, I thought about it and wondered if that would be clearly indicated, and I didn’t do that because that’s historically been a group that has been the subject of clinical research for decades. However, it’s fair to say that this group is probably smaller than the subset with SCLC is smaller than the squamous cell NSCLC population, and also that investigators and companies are considering clinical trials in SCLC to be less and less feasible, so having a concentrated place where patients and potential trials could find each other would probably be a good thing.

    I also think the group of patients with mesothelioma are understudied but need to band together to accelerate the rate of clinical research.

    In terms of a press release or fanfare, I suppose we could, but I think it’ll be more powerful for the people here who know about this to mention it over time to other people in different online communities over time, more of a slow burn than a trumpet blare. Many new people come into these communities all the time, so if people in the lung cancer community just know where to find and how to join the list, I think it’ll serve its purpose. I also don’t want to do any chest beating or claim ownership of a group that I think really belongs to its members. Finally, at this point there aren’t specific trials necessarily for all of these groups — it’s really an initial effort to lower the barriers to them being studied better.

    Nevertheless, if people think this is too tentative, we can certainly look into consciously working to publicize these efforts in a systematic way.

  • reginac says:

    Am I considered a nonsmoker? I have a 1/2 pack a day history for 9 years, quitting in 1980 (coming up on my 30th anniversary on the 25th of this month). I would suppose that nonsmokers encompass folks who quit anytime, but may there is a definition out there. So far I don’t have any markers of any sort.

  • dfourer says:

    Thank you Dr. West for setting this up. I added my name to ALK+ group. I was actually just logging on to figure out what to do, and I see that it is all done. I see 29 posts in all categories in just a few days.

    You may recall that I waited a long time to get the genetic testing. I did test positive and I am in the phase II trial at Univ of Chicago. No dramatic recovery but I am OK.


  • catdander forum moderator
    catdander says:

    off topic…
    that’s great David, glad to hear you’ve got good possibilities coming your way.

  • Ellen says:

    It’s a great idea, but I do think you should reach beyond the internet. A press conference would be useful. First, there’s not enough press about lung cancer. Second, not everyone has a computer or is computer savvy. To get maximum participation anong the broadest population, use every means possible.

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