Transcript Details This is a transcript of a continuing medical education (CME) activity accessible on the ReachMD network. Additional media formats for the activity and full activity details (including sponsor and supporter, disclosures, and instructions for claiming credit) are available by visiting: https://reachmd.com/programs/cme/case-review-case-treatment-naive-patient-advanced-nsclc-smokermetastatic-squamous-cell-tumor/7880/ Released: 01/26/2016 Valid until: 01/26/2017 Time needed to complete: 15 Minutes ReachMD www.reachmd.com info@reachmd.com (866) 423-7849 A Case Review: Treatment-Naïve Patient with Advanced NSCLC: Smoker with Metastatic Squamous Cell Tumor ANNOUNCER OPEN: Welcome to Project Oncology on ReachMD. This segment, entitled A Case Review: Treatment Naïve Patient with Advanced NSCLC: Smoker with Metastatic Squamous Cell Tumor is provided by Prova Education. Joining us today at the University of Chicago Medicine is Dr. Everett Vokes. Dr. Vokes is Physician-in- Chief, University of Chicago Medicine and Biological Sciences as well as the Department Chair. Joining Dr. Vokes is Dr. Tanguy Seiwert. Dr. Seiwert is Assistant Professor also at the University of Chicago, as well as the Associate Program Director for its Head and Neck Cancer Program. Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure 2018 ReachMD Page 1 of 5
statements as well as the Learning Objectives. Or if you re listening to this as a podcast, go to this activity on ReachMD.com forward slash Project Oncology. Everett, I have another case of lung cancer. This is a 55-year-old woman with a 25-pack-year smoking history and she presents with a pneumonia. She had a workup done and workup reveals squamous lung cancer on histology and, in this case, because it s a squamous tumor, there s no molecular testing done. The question now is, you have a patient with metastatic squamous cell tumor. She has disease in both lungs, how would you approach this patient with squamous cell lung cancer? Thanks Tanguy. So, you re right, in many practices a newly diagnosed squamous cell cancer in a smoker, genetic testing would not be done. We actually do adhere now and there s relevance maybe to doing that for second-line treatment and beyond, and we can talk about that, but certainly so far this is a typical lung cancer, the way we would have seen it for decades in a heavy smoker. My guess is with a squamous cell lesion she has a central lesion; she has a post-obstructive pneumonia. That s how she s diagnosed. It turns out to be Stage IV. So treatment is palliative and there are no mutations, or she wasn t tested. So, what we re left with is classic chemotherapy, doublet chemotherapy. In a squamous cell tumor, the use of bevacizumab is not considered. It is associated with fatal hemoptysis. So it would be a doublet treatment and in the Landmark trial that established pemetrexed, gemcitabine was actually superior in this group of patients. So, one option would be a carboplatin or cisplatin-based regimen with gemcitabine. Taxol would be an equally good choice. That was not included in that study, so giving her a cis or carbo with paclitaxel, or for that matter docetaxel, would also be totally acceptable. And that is how we would treat her here at the University of Chicago. Her odds of going into remission are around 30%, another 30% who have stable disease, and 30% to progress by cycle 2 and then need to go on to additional treatment. Yes. Very good. So, she gets treated with cisplatin. She has normal renal function, and gemcitabine and she does well for 6 rounds. She then takes a break from the chemotherapy and then 3 months later is diagnosed with progressive disease. How would you now go about treating her? 2018 ReachMD Page 2 of 5
So, that is very interesting. She got 6 cycles, so she had benefit, and the number of cycles is still somewhat controversial. So, at some centers it might be 4 cycles, but then in squamous, the role of maintenance chemotherapy is much less well established. So, in an adenocarcinoma that would be typically the case 4, but sometimes 6, cycles of doublet, and then continue unless there s been progression, usually with pemetrexed. In squamous, we re not so sure about. There are data for erlotinib but it s not usually administered. So, giving her 6 and then a break, I m comfortable with that. And now that she s progressed we have recent very relevant literature from the New England Journal, and that was a direct comparison second-line in this group of patients, of docetaxel versus nivolumab and the nivolumab was statistically highly superior, both for progression-free and overall survival. So that now would clearly be the second-line therapy of choice for her. Yes. There s now two approved immunotherapies for second-line lung cancer, including both lung adeno as well as lung squamous cell tumors. How would you compare the 2 agents, nivolumab and pembrolizumab which are both now approved? Yes. Tanguy, you re absolutely right. So, nivolumab had the randomized comparison. Pembrolizumab is also approved and is numerically similarly active. It looks just as active and similar, but it s not based on a randomized trial, it s based on a very large cohort Phase II trial, and what they then did is look specifically at those patients who had expression of PD-L1, and so that is their approval indication. So, for pembrolizumab, a test is associated with that. It s the Dako test where expression of PD-L1 has to be shown, and then that drug is also FDA approved. So, some institutions may have the test in-house and, if so and it s over-expressed, then the pembrolizumab is a very good choice. If the test has not been done, pembrolizumab might be just as active as nivolumab, but the study wasn t done in the same fashion and likely it would then become nivolumab. So she s treated with an immunotherapy. She s treated with nivolumab, in this case, and she has disease stabilization. The tumor stops growing and has stable disease for about 8 months which is actually very, very good for a second-line setting; however, then she starts to show progression again, and the disease actually starts to grow slowly. Like, how would you approach this patient now, given that she shows evidence of progressive disease, but the characteristic of the disease has somewhat changed? 2018 ReachMD Page 3 of 5
So, let s assume, or I assume, that it s not in the brain, which could happen and needs to be imaged, and that it is, however, in new systemic lesions, so true progression. At that point, what we know is we should probably stop the immune therapy. We have not advanced knowledge whether there s a role to continue it or to add other immune therapeutic drugs to it; that s investigational. So, what are the other standard options? So there is still docetaxel, but there was a recent positive trial where a drug called ramucirumab, which is a VEGFR inhibitor, would be added to the docetaxel and that showed a survival advantage, not very large, but in the vicinity of about 2 months. So that might be the next option to use. And of note, we talked about first-line not using bevacizumab or a VEGF inhibitor; that can be done second-line with ramucirumab, and the study was specifically open to patients with squamous cell tumors. There s also an interesting study going on within the Cooperative Group system and that s a second-line study. It s the so-called Lung-MAP trial where patients are tested for mutations with squamous cell, so that s going back to that initial tumor where that might have been done, and if they then have a match and it s a 5-arm trial, where several defined mutation-driven tumors have a specific trial, and then there s, for those who don t have that, an open trial. The arms tend to change a little bit and are adjustable, but that trial might be another option for her. Yes, it s remarkable that you mentioned two positive Phase III trials which really is a big event, one obviously being nivolumab versus docetaxel. Striking benefit with a really amazing hazard ratio of 0.6 and then the study with ramucirumab which was a much less positive, but still positive trial. So, I think it is good to see that actually both of these apply to squamous cell tumors, where we ve really seen very little progress in recent years. So, maybe to finalize this, obviously immunotherapy shows a large benefit for lung cancer, especially for lung squamous cell tumors. Would you consider moving the immunotherapy to the front-line setting and, I think there are approaches now being investigated potentially doing that, how would you look at this, and do you think that s the right way to do it, and how could one imagine this would actually play out? Should this be as a single agent, or should this be in combination with chemotherapy or other immunotherapies? Well, there s one more twist, since we re talking about positive-randomized trials, and that is a recent trial with FDA-approval pending or just about to happen, and that is the addition of necitumumab to cisplatin and gemcitabine. And that necitumumab is again an EGFR-inhibiting antibody. Cetuximab didn t quite make it in that setting. Necitumumab had a positive trial and it s been reviewed by ODAC and the FDA, and so that is worth staying informed about since that would likely be another first-line 2018 ReachMD Page 4 of 5
option, of course for a patient who is after getting the third drug. Having said that, what was the question? I managed to get that in because I forgot it at first. We have a lot of very striking data from immunotherapy in the second-line setting for lung cancer, in particular, for lung squamous cell tumors. There is interest now to move immunotherapy to the first-line setting and the question is, is this appropriate and if we do it how should we do it? Should we combine it with chemotherapy? Should we do it, and in which population, or maybe in combination with another immunotherapy? What are your thoughts? And obviously this is an emerging field of certain interest. Yes, I think you really described all the options. It s very, very intriguing to do this. The limitations of chemotherapy are self-evident, so if we could improve what we do first-line, it would be wonderful. All of what you mentioned is being investigated. So, first-line trials of single agent in comparison to chemotherapy, first-line trials of adding a PD-1 inhibitor to chemotherapy versus chemotherapy. I think within a year or so we will have much more data in that space that should guide us in much better ways. Thank you, Dr. Vokes. Thank you. ANNOUNCER CLOSE: You have been listening to Project Oncology on ReachMD. To earn your CME credit, please take the post-test and activity evaluation. Or if you re listening to this as a podcast, go to ReachMD.com forward slash Project Oncology. 2018 ReachMD Page 5 of 5