TRANSCRIPT: Ask Us Anything about Precision Medicine and Lung Cancer with Dr. Howard Jack West and Janet Freeman-Daily

TRANSCRIPT: Ask Us Anything about Precision Medicine and Lung Cancer with Dr. Howard Jack West and Janet Freeman-Daily

Hello everyone and welcome to the 2nd Free to Breathe HealthUnlocked Ask Me Anything event! We also want to welcome our very special guests Dr. Howard Jack West and Janet Freeman-Daily.

Go ahead and start typing your questions as a reply in this thread below. You can either ask a question to both of our guests, or you can ask Janet directly by tagging her with @JFreemanDaily, or ask Dr. West by tagging him with @JackWestMD

Once our experts see your comment, they will reply back. To know if they replied to you, simply refresh the page and you will see an orange indicator next to notification button at the top of the page (the bell icon). NOTICE: This is just a text conversation; no video or audio needed!

Once our hour is complete, this thread will be locked so that no more questions will go through, so be sure to ask your questions before the event is over!

More about our experts:

Dr. West has published numerous articles in peer-reviewed literature and has authored several book chapters. He also now serves as the Web Editor of JAMA Oncology and is on the editorial boards of Journal of Clinical Oncology, Journal of Medicine, Clinical Lung Cancer, and Journal of Thoracic Disease, in addition to serving as an author of multiple lung cancer-related sections of UpToDate and as a reviewer for more than a dozen professional journals. Dr. West leads a wide range of clinical trials and has been actively involved with the SWOG Lung Cancer Committee as a Study Coordinator/Principal Investigator. Dr. West founded and continues to serve as President of the nonprofit organization Global Resource for Advancing Cancer Education (GRACE), a source of timely, free information for patients and caregivers dealing with cancer that currently receives over 50 thousand visits per month from over 100 countries around the world. Dr. West is also working to develop telemedicine-based practice patterns to broaden the range of treatment options for cancer patients through the Swedish/Providence network.

Janet Freeman-Daily, MS, ENG, was diagnosed with advanced non-small cell lung cancer (NSCLC) in May 2011. After two chemotherapy regimens and two radiation protocols, her cancer became metastatic. She used information obtained in online forums to get her tumor tissue tested for newer molecular markers and find a clinical trial, and has had No Evidence of Disease since January 2013 thanks to precision medicine and social media.

After applying her MIT and Caltech engineering degrees to a career in aerospace systems engineering and new business for two decades, Janet now is a patient activist who uses her communications and science background to translate the experience of lung cancer treatment and research for others. Her advocacy work includes writing an award-winning blog at, co-moderating Lung Cancer Social Media (#LCSM) Chat on Twitter, serving on local and national cancer research and working groups (among them National Cancer Institute, President’s Cancer Panel, and University of Colorado NCI SPORE), leading the Global ROS1 Initiative ( with other patients, and speaking at oncology and medical conferences.

Thank you all for participating and enjoy the event!


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71 Replies

  • Hi all! Looking forward to seeing your questions. If you don't have a question, tell a good precision medicine joke!

  • Is there a video feed, or is Janet and Dr. Jack simply typing in their respective cubicles?

  • It's just text responses. Great question!

  • Asked by dave9435 :

    Can I ask my question ahead of the "Ask us Anything" discussion? I'm a patient who has received targeted therapy for 3.5 years. I have 2 stable tumors in my lungs, and two small punctates in my brain. They continue to respond to Alectinib (I'm ALK+, but my situation of acquired resistance occurs for all targeted therapy patients). I have progression (started last summer) in my liver which has not responded to 2 other TKI medicines, although the other tumors continue to respond. At the time of progression, a biopsy showed the liver mets were EML-4 ALK, no fancy mutations. The progression apparently is not feeding on the ALK protein. So I'm now on chemo plus Alectinib.

    My questions are how common is this typed of acquired resistance in targeted therapy patients, and are there scientific methodologies for choosing the most effective chemo agents? Patients who follow TKI therapies know there is active discussion about the order of which medicines to take, first line versus 2nd/3rd generation. But when you have acquired resistance, that becomes a somewhat moot point.

    Last, I was reading about a clinical trial medicine, a potent selective small molecule inhibitor of Axl called BGB324 as a possible agent to re-sensitize my cancer (again, not just ALK but other targetable mutations). Has there been any news about this trial presented at professional conferences that may show it is promising?

    Thank you!


  • JackWestMD's response below:

    dave9435 ,

    At this time, it isn't yet routine to do repeat biopsies for ALK acquired resistance, which we expect to occur in nearly every patient over a matter of months to years. Because relatively few oncologists routinely test for mechanism of resistance, we don't know much about it except that there are far more diverse mechanisms of resistance than in EGFR mutation-positive patients, for instance, when one resistance mutation (T790M) is seen in more than half of patients who develop resistance.

    Accordingly, some researchers are doing work on whether one specific agent is more likely than others to work on a specific mutation, but we're not really there yet. We definitely don't have any mechanism for picking a specific chemo, but the combination of cisplatin or carboplatin with pemetrexed (Alimta) tends to be a good one for ALK+ patients.

    I haven't seen work on BGB324 yet, but I'll be on the lookout at upcoming meetings.

    Good luck.

    -Dr. West

  • Hello! It was great news that a new drug targeting ALK+ lung cancer was FDA approved last week. What does this mean for patients? Do we know which drugs should be used first?

  • Yes, great news that brigatinib (Alunbrig) was approved for ALK+ NSCLC! It does get into the brain. Jack is addressing some of the "which drug in which order" questions in his response above to davedave9435. When choosing the next drug to take after progression occurs, it helps to consult an expert doc who has treated many ALK+ patients (like Jack, Dr. Ross Camidge, or Dr. Alice Shaw).

  • Brigatinib is definitely an active agent, another 2nd generation ALK inhibitor usually well tolerated and with a progression-free survival over 1 yr after crizotinib, which is encouraging. Practically speaking, though, with alectinib and ceritinib already available as 2nd gen ALK inhibitors, and with alectinib likely to soon move to first line after the positive results of the ALEX trial comparing alectinib to crizotinib as initial treatment (press release reports alectinib is better, but data not reported yet), brigatinib will likely be relegated to later use.

    We don't know how active brigatinib will be after alectinib or ceritinib -- probably considerably less than after crizotinib, which is a less potent ALK inhibitor than those 2 -- but it will definitely be tried. We'll need to see whether it adds benefit after progression on a prior 2nd generation ALK inhibitor. And in the next year, we should also see results of a trial of brigatinib vs. crizotinib as first line that may make it look even better than alectinib.

    For now, it's another good option, but it's not clear how valuable it will be for most ALK+ patients if they've already progressed on another drug with very similar activity.

    Good luck.

  • Should all patients with lung cancer get tumor testing?

  • The National Comprehensive Cancer Network (NCCN) (as well as the soon-to-be-updated CAP-AMP-IASLC molecular testing guidelines) state all patients who have non-small cell lung cancer adenocarcinoma should get tested for EGFR, ALK, and ROS1. Patients who are eligible to take immunotherapy might also benefit from PD-L1 testing.

    Unfortunately, we do not yet have useful tumor testing for small cell lung cancer, because we do not have targeted therapies for SCLC, but research is progressing.

    NSCLC patients who do not have EGFR, ALK, and ROS1, and who are able to travel to clinical trials, might want to ask their doctor about more extensive tumor testing for mutations such as BRAF, which do have clinical trials.

  • The vast majority of patients should be tested for at least one marker, such as PD-L1 (which predicts for probability of a good response to immunotherapy), but patients with a non-squamous non-small cell lung cancer should also generally be tested at least for markers like EGFR, ALK, and ROS1. Beyond that, there's some reason to debate how useful broad genomic testing for dozens or hundreds of genes really is, because we don't have a good answer to what to do when we find most of these, but the field is moving toward finding a broader range of targeted therapies for more and more molecular targets. Because of this, it is certainly a strong consideration to do broad genomic testing, especially if patients may have access to clinical trials with novel drugs.

  • Yes

  • If a patient hasn't had their tumor tested but wants to, what's a good first step?

  • The best first step is to talk to your doctor. Since tumor testing for NSCLC is standard of care, your doctor should know about tumor testing. If they don't, get a second opinion, preferably from a major cancer center that is more likely to be familiar with tumor testing. If your doctor refuses to discuss testing, find another doctor!

  • I agree it's completely appropriate to talk with your doctor to ask why. There may be a reason to not do testing, such as there not being enough tissue or a patient having early stage disease, where further treatment may not be needed or appropriate. But it's definitely worth having a discussion of whether molecular testing is appropriate and, if not, why not? If you don't agree with the answer, it's very reasonable to seek a second opinion.

  • I'll also ask a question from a patient "I’ve heard that immunotherapy doesn’t work well for patients with EGFR or ALK mutations. Is that true?"

  • Some EGFR patients have been responding to immunotherapy, but the percentage of EGFR responders is less than the average (I believe).

    Immunotherapy doesn't seem to work for those of us with ALK or ROS1 mutations--apparently the immune systems white cells don't seem to penetrate ALK and ROS1 tumors well, so the immune system doesn't attack the tumors.

    Researchers are looking for combinations therapies that might make EGFR, ALK and ROS1 more responsive to immunotherapies.

  • Yes, that's been a converging conclusion from most of the immunotherapy studies, but it doesn't mean it isn't worth trying. Rather, I would just say that it would lead me to prioritize other options and move immunotherapy to a later choice for most patients with a driver mutation.

  • Why are patients not told conventional cancer treatments can rule out immotherpy

  • To my knowledge, this is not true. Conventional cancer treatments do not rule out immunotherapy. However, if a patient has a conventional cancer treatment and their general health declines below a certain point, their doctor may decide they cannot tolerate immunotherapy (or other treatments).

    Perhaps you can clarify the conventional treatments to which you're referring?

  • Hi thanks have read alot about conventional treatments trashing cells thus immunotherapy would not work as cella dna damaged.

    Also issues of blood transucusions or lack off

  • I haven't heard anything about conventional treatments "trashing cells." I'll keep an eye out for articles about that.

  • Jeff, my local hospital is making immunotherapy standard second line after patient has progression on platinum doublet

  • Yes, I agree that this isn't true. there are currently 3 immunotherapy agents all approved for treatment after initial chemo for advanced NSCLC, and immunotherapy is sometimes recommended after chemo for extensive stage small cell lung cancer.

  • Hello, JFreemanDaily and JackWestMD, thanks so much for taking the time to do this AMA.

    The past two years have been jam full of remarkable treatment advances that have changed the standard of care for many people with advanced lung cancer. Can our researchers keep up this pace? As I scan the news, it seems like right now we are seeing more duplicative drugs and random searching for better immunotherapy combinations as the main research efforts.


  • I think it would be a fortunate problem for researchers to not be able to keep up the pace of fantastic progress, but I don't think that's the case. The reason there are nearly redundant trials is that the vast majority of the clinical research is sponsored by companies who want THEIR drug tested in the same trial design as many others, even if it's just a "me too" study. There is more than enough motivation and ability to ask novel questions, but the bottleneck and the driver of redundant research is the reality that most research is being funded by pharma companies. If we want that to change, more work has to be sponsored by the NIH, advocacy groups, and other non-corporate sources.

  • So that is where donations to lung cancer groups that focus on funding research, like Free to Breathe, can really make a difference.

  • The pace of cancer research is actually accelerating as new immunotherapy approaches and drug combinations are being investigated. I personally don't see it slowing down anytime soon! (Praying the NIH funding holds)

  • dave9435 ,

    At this time, it isn't yet routine to do repeat biopsies for ALK acquired resistance, which we expect to occur in nearly every patient over a matter of months to years. Because relatively few oncologists routinely test for mechanism of resistance, we don't know much about it except that there are far more diverse mechanisms of resistance than in EGFR mutation-positive patients, for instance, when one resistance mutation (T790M) is seen in more than half of patients who develop resistance.

    Accordingly, some researchers are doing work on whether one specific agent is more likely than others to work on a specific mutation, but we're not really there yet. We definitely don't have any mechanism for picking a specific chemo, but the combination of cisplatin or carboplatin with pemetrexed (Alimta) tends to be a good one for ALK+ patients.

    I haven't seen work on BGB324 yet, but I'll be on the lookout at upcoming meetings.

    Good luck.

    -Dr. West

  • Thank you! It was great seeing you and hearing your talk at the Hope Summit last weekend. Thank you for your commitment to lung cancer patients!


  • Can't get on ;(

  • You are in it now lyzrockgirl1

    It is just a text conversation. Type your question here and they will respond with a text reply here.

  • What is PD-L1 testing?

  • PD-L1 is a protein that appears on the surface of some cancer tumors. Tumors that express a high level of this protein are more likely to respond to a certain type of immunotherapy called PD-1 blockade (Opdivo and Keytruda are PD-1 blockade drugs). Testing for PD-L1 is required for patients to be eligible for some drugs. Your doctor can order this test on a sample of your tumor tissue.

  • PD-L1 testing is required for first line (initial) treatment with immunotherapy, but it is not required for all agents if immunotherapy is given in the second line or later setting (after prior chemo).

    In essentially all immunotherapy trials in lung cancer, the probability of a good response is higher in patients with high PD-L1 staining on their tumor. However, it's not a great biomarker. PD-L1 is neither necessary nor sufficient for a response to immunotherapy. Some patients with very high level PD-L1 don't respond at all to immunotherapy (response rate is ~50% at best in high PD-L1 patients), and even in those with little or no PD-L1 staining, a minority of patients (maybe 5-10%) can respond quite well.

  • JFreemanDaily Your story is powerful! Could you please talk about your diagnosis and how long it took between diagnosis and getting your tumor tested?

  • I was diagnosed in May 2011 with advanced non-small cell lung cancer. At that time EGFR testing was standard of care, and my team ordered that testing without any action on my part. ALK testing was not standard of care because no approved drug existed. I asked my team to test for ALK also, and they did. I was negative for both.

    I learned from online patients about other mutations, and after my first progression, arranged to have my tissue tested in a clinical trial (Lung Cancer Mutation Consortium Protocol) that looked at 10 different genes. My doctors helped me get my tissue samples to the trial. Alas, I was negative for all of those mutations as well.

    I learned about a new gene test for the ROS1 fusion from an online patient (shoutout to CraiginPA). After my second progression, I arranged to have my tumor tested for ROS1 by the institution who ran the 10-gene panel (University of Colorado), and I was positive! I've been in a clinical trial (taking crizotinib for ROS1) since November 2012, and have had No Evidence of Disease for 52 months and counting.

    New genes are being discovered at an increasing rate. It pays to learn from other patients online about new research!

  • That

    This is wonderful news--may it continue!

  • My father has extensive SMLC and he is doing well via body but now the see very 3 little dots in his head and want to do radiation but the immune therapy trial worked. He chest has nothing. He is almost 80 and don't want to effect him cognitively . He is already showing chemo brain.

  • We generally presume that the threat of brain metastases in small cell is throughout the brain and favor whole brain radiation in small cell patients with brain metastases, but there is far more concern now about cognitive issues from brain radiation than in the past (part of this is that more patients are living long enough to have late side effects we never saw before our therapies became more effective).

    In some selected patients with a few brain mets in the setting of small cell, I and my radiation oncology colleagues have pursued focal radiation just to the brain mets, followed by lower dose radiation to the rest of the brain (what you'd give for prophylactic brain radiation). You could perhaps omit that, but growing brain mets also cause their own problems, so I don't think that should be minimized.

    Good luck!

  • Thank you! Do you think the drugs that help with memory help? Do you think the immuno therapy drugs can show activity "Pseudo progression" in the brain since it can pass through the blood brain barrier?

    I appreciate the feedback/

  • I have "chemobrain" symptoms from two different lines of chemo and now targeted therapy (though it hard to know whether any of it is menopause, mommybrain, or just getting older). My neuro-oncologist recommended I take extended-release methylphenidate (Ritalin) to help with the focus issues, and I really think it helps. You might ask your doctor about it.

  • I think the agents for memory are minimally helpful at best. Immunotherapy for small cell is still not well enough studied to know what to expect, but I personally wouldn't presume that they will be helpful in the brain, based on the very, very little we know about immunotherapy and responses of brain metastases (POSSIBLE responses, but not studied well enough to say more).

  • Did these spots appear after the immunotherapy trial? If the immunotherapy trial is effectively treating the brain, talk to his doctor about whether radiation is needed. If the spots appeared after the trial, perhaps he can consider stereotactic radiation to the few mets. Treating brain mets after a response to immunotherapy is new territory. You might want to consider consulting with an immunotherapy expert about this.

    Best hopes for a good outcome!

  • They did appear after though supposedly the drug can be in the system for 100 days.

  • Thank you!

  • QUESTION for both Dr. West and Dr. Freeman. I'm a 2 yr. 4 month lung cancer survivor in remission from lung surgery. My 2 mm noodle was picked up on a routine mammogram by a vigilant BWH radiologist, and long story short, when it doubled to 6 mm in 2009, I was referred to my thoracic surgeon who promised it would never reach a cm--but was in a location in my lower left lobe that couldn't be reached by biopsy, but he and I both know what it was (then called BAC), not adenocarcinoma.m In De. 2014, I had a composite basilar segmentectomy of the 9 mm x 7 mm tumor and also a bronchoscopy. Genetic testing confirmed the K-ras mutation, subtype pG12A. MY QUESTION IS ABOUT STATUS OF RESEARCH on the KRAS GENE (1st oncogene ever discovered in 1982 and still not cracked). Even Stage 1a TN0 patients like me have a 40-45% chance of reoccurrence within the first 5 years. I'm at one of the best cancer hospitals in the US & probably in the world, and my thoracic oncologist is a co-leaderof the "Dream Team" to figure out KRAS. I'm wondering if you have any new data or are collaborating with this US effort on KRAS?

  • I'm not, but every lung cancer specialist is interested in finding something that would work against KRAS. There are certainly trials ongoing looking at treatments vs. KRAS (I'm hoping to open one with an agent called selinixor, but there are some others), but it has been a hard nut to crack. Not for lack of trying, and nobody's giving up. It would be a giant step for the lung cancer community to find an effective targeted therapy for KRAS mutations.

  • Sorry you're having to deal with KRAS+ NSCLC, but it sounds like you're already connected with one of the best sources of information about KRAS. I wouldn't have anything new to share that your doc hasn't already seen at conferences. Best hopes for effective treatment!

    P.S. I'm not a doctor, just a science geek with lung cancer who obsesses over staying alive and helping other patients do so.

  • Thank you too Ms. Freeman... I've worked years in medical fact-checking and copyediting (biology especially), so research everything that affects me (and also other cancers I hear about from friends and family if they ask). I'm also now in intensive treatment (responding well) for a B-cell follicular lymphoma (same hospital, different team): combo of one immunotherapy and one chemo. Can't be cured but can be made a chronic condition, followed and treated if necessary. The links I get on research at NCI and NIH, Medline, Medscape, info from good cancer organizations, etc. --I guess I'm sort of a "cancer geek" too... My life has twice been saved, and the process continues... I wish you all the best with your lung cancer and hope it's one of the treatable genes that's driving it.

  • I'm fortunate that my lung cancer is driven by a ROS1 fusion, and I'm responding well to the one approved drug. Thanks for your support!

  • found my way in finally!

  • Welcome, welcome Denzie! Glad you are here =)

  • Hiya Denzie! Good to see you here.

  • Can a patient who'ss had WBR have Stereotactic brain radiation?

  • Usually. However, whether a patient is eligible for stereotactic brain radiation also depends on the volume, size, number and location of brain mets.

  • Is tumor testing covered by insurance?

  • Testing NSCLC patients for EGFR, ALK and ROS1 is usually covered by insurance because it's in the standard of care. Broad genomic testing (like Foundation Medicine) often isn't, but sometimes the testing agency can help find a way to pay for it.

  • I agree with Janet, and I'd just add that many research-focused centers may offer genomic testing in the setting of a clinical trial that wouldn't charge for the testing. Could be a good option to get the testing without the cost.

  • And what is the point of double blind placebo, I thought placebo were obsolete?

  • Placebo controlled trials rarely give NO treatment. They give whatever the standard treatment is, with either something added or a placebo. So people would never get placebo only unless the best available treatment now is supportive care alone.

    Placebo controlled trials are not evil. We very often do trials of standard treatment X with either new drug Y or placebo (so the placebo arm is still getting our best current treatment of standard treatment X) and find that the placebo arm does BETTER than the arm getting some combination of standard treatment plus new drug. It's even possible that a new treatment will be worse than supportive care alone if the new drug adds side effects but no benefit. The best and sometimes only way to know that a new treatment is effective is to have a placebo control, and sometimes the placebo arm does far better.

  • But usually the standard care of treatment has halted because of the study. I guess i am confused. Fortunately, my father had the combo drug and he had to stop Chemo but the drugs did give him a rash and the doctor thought his cancer progressed so the trail threw him off. But actually his next scan showed little to no cancer.

  • Patients in cancer trials usually receive, at a minimum, the standard of care. It's very rare to use actual placebos in cancer trials. They might be used in, say, a vaccine trial in a population of patients whose cancer has been treated and is under control; in that case, the patients who are not receiving the vaccine will still be receiving standard of care.

  • What are the most promising clinical trials of precision medicine right now?

  • I think trials like the ASCO-supported TAPUR trial that enables broad genomic testing and then pairs results with targeted therapies are especially valuable. There is also one called the MATCH trial that is similar, one in squamous cell called the Lung-MAP trial, and a collection of related trials called ALCHEMIST that is looking at post-operative treatments for earlier stage NSCLC guided by molecular marker results.

  • That is great. Thank you!

  • I have inherated DNA issues mainly DNA brakes guess like form of mitosis but cant really remmber name of it.

    Twice i have been told i have lung cancer that turned into granuloma

    Lucky eh ... Would my dna and brakes save me from cancer but not lung granuloma.

    O am immunty compromised and due igm immunty therpy but do worry as treatments can be as bad

  • I'm sorry to say that I don't know anything about that. Not to say it's impossible, but I don't believe that's well studied enough to make any predictions about developing cancer or how you would respond to different cancer treatments.

  • I'm glad you didn't actually have lung cancer. Without knowing more about your inherited genetic condition, it's hard to comment. We have very little data about inherited risk factors in lung cancer, even though we know of families in which several members have had lung cancer.

  • That is all for our Ask Me Anything session about precision medicine and lung cancer. Thank you to our amazing guests, JackWestMD and JFreemanDaily for answering EVERY question asked.

    And a big thanks to everyone who participated. We will close this thread and turn it into a transcript that will help others in the future!

  • Thanks for all your questions, and for inviting me to participate! I'll be around on the community if you have other questions.

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