Advances in Targeted Therapies for Non-Small Cell Lung Cancer - Episode 22

Looking Towards the Future of Molecular Testing and Additional Treatment Options for Patients with mNSCLC

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The panel closes by summarizing recent advances in the field and shares hopes for future improvements in molecular testing and treatment options for patients with mNSCLC.

Joel Neal, MD, PhD: I think it's incredibly exciting that we now have 10 targets with targeted therapies in non-small cell lung cancer. Many of them frontline, a few of them second line, but no doubt emerging and moving into that first line space as we get more highly active therapies that are extremely well tolerated, like mobocertinib and amivantamab and selpercatinib and pralsetinib.

Zosia, any other thoughts of advances overall you're excited for as we come toward the end of our program?

Zosia Piotrowska, MD: No, this field is moving in just a very exciting direction. I think the area of overcoming resistance to all of these therapies is kind of the next frontier and think there certainly see a lot of next generation tyrosine kinase inhibitors coming out for the various targets, but I'm also excited about many of the kind of less targeted approaches like antibody drug conjugates, for example. And I think in the future, hopefully we'll have kind of a broader armamentarium of agents to use for these patients as they kind of progress through treatment, as they might acquire resistance to the approved targeted therapies. So, I think certainly thinking about the targeted therapy options but also thinking more broadly about other ways to treat these cancers is a really exciting next step for us all as a field, I think.

Joel Neal, MD, PhD: Michelle, any advice for molecular pathologists or other pathology colleagues there who may not have the privilege of 100% dedicated effort to molecular pathology in de-convoluting and following all of these changes in not only non-small cell lung cancer but across all of the other types of solid tumors with new approvals?

S. Michelle Shiller, DO, AP/CP, MGP: So, a few key takeaways there. One is I try to direct them all to NCCN.org. In my opinion, across all professional organizations in this space, they are the nimblest at updating the guidelines as per FDA approvals and also giving insight as to what's happening in the research space. So the caveat I tell our pathologists now is when you're signing out your case and it's a malignant diagnosis, just peek into the guidelines, see what might be relevant to this case that if you don't have some mechanism already established with your local providers for next-step testing, maybe contact them and say, hey, while I have this case out, is there something you want me to make sure we get taken care of before the patient follows up with you? I really feel like that will really increase that team-based effort in the report and provide that service to you guys, that that is what we're here for as pathologists. I also, like Zosia, I'm excited about the promise and potential for antibody drug conjugate therapy. And aware of some of the pending indications even in MET amplification itself, and also some of the testing approaches that are being considered. When I listen to that and think about it and even dialogue with some of the parties that have a stake in this place, the stakeholders, one area of concern that I have, we've a little bit touched on this, and that is clinical background once you're receiving a case. So, if we're going to be in a scenario where we need to do some more immunohistochemical-based testing, which is more relevant in many cases to antibody drug conjugates but we're dealing with these very small, tiny tissue biopsies, we've gotten very good. That's one of the beautiful things about NGS. It answers so many questions at one time, but it can't answer all of the questions. Not one technology is ever going to be able to do that. So, I think everyone's in this perfect world at the moment where we have this algorithm and this flow of how the specimen goes through the lab, but I think we're going to start getting little branches on our tree of non-small cell lung cancer workup. And so, if we know the scenario in which we're receiving a specimen, prior EGFR mutation, on an EGFR TKI and now progressing, then we know, OK, well, we may be looking at a potential MET amplification as a for instance. So instead of doing a TRK IHC slide to screen for that before we run our NGS, we actually allocate that to MET IHC or MET FISH and then also run NGS. We've also recently put some information out there just looking at our concordance rate between at least NGS as a screen with MET amplification as one of the biomarkers that I'm referencing and then confirmation by MET FISH. So, a lot to still learn. Antibody drug conjugates, definitely wonderful the way these drugs work. We just need to all kind of talk about how we're going to approach that from a tissue stewardship perspective for the patient.

Joel Neal, MD, PhD: Yeah, I think the emerging era of proteomic testing and more IHCs for ADCs is something that we'll be learning a lot more about over the next few years, I think. Lauren, it's clear that you have incredible expertise in the provider realm, working with all of these drugs. I want to turn to the patients for just the last minute and think about how we have great advocacy groups, support groups. The Exon 20 Group for EGFR exon 20 insertions. The RET Renegades out there for patients with RET-positive non-small cell lung cancer. What's your advice to patients out there living with these diagnoses, patient advocates, and the message of hope for the future?

Lauren Welch, MSN, NP-C, AOCNP: Absolutely. One of the great privileges of working in a Phase 1 clinic is I get to meet a lot of these patients who have found out about our clinical trials through the advocacy group that they're a part of. That's immensely rewarding, especially when their therapy has stopped working and they've learned that there's a next generation ROS1 inhibitor, a next generation ALK inhibitor available. And so, I would just encourage, I encourage all my patients to get engaged with patient advocacy groups. There are general lung cancer patient advocacy groups and then so many different subcategories based off of mutation results. And those groups are dynamic and have so many resources and ways of not only offering support to the patient, also to the caregivers, because they're on this journey too. And the advocacy groups are so instrumental in helping the patient get plugged in to the right research site. So, I would encourage anyone who has been diagnosed with non-small cell lung cancer or who has a loved one who has been diagnosed with non-small cell lung cancer to look into those advocacy groups.

Joel Neal, MD, PhD: Thank you so much. Yeah, I think it's always important to think about the wider audience. Though this program may not reach them, I hope it does, as well as all of our collaborators who have developed these drugs and support these programs. Thank you. Also, thank you to our panel for your thoughtful case presentations, the informative discussion we had around those cases today, your unique insights from all of your different institutions. It's a pleasure to connect with people across the country and virtual has brought us closer together than ever. To our viewing audience, thank you so much for joining us today. I hope you found this a valuable use of your time and that you can use the practical knowledge that you acquired in your clinical practice. Thank you.