GRACE :: Lung Cancer

immunotherapy combinations

Denise Brock

Lung Cancer Video Library – First Line Combinations, Immunotherapy with Chemo

GRACE Cancer Video Library - Lung



We welcome Dr. Luis Raez, MD FACP FCCP, Chief of Hematology/Oncology and Medical Director at Memorial Cancer Institute, and Clinical Associate Professor of Medicine at Florida International University with 2017 updates to our Lung Cancer Video Library.  In this recent video for GRACE, Dr. Raez discusses First Line Combinations, Immunotherapy with Chemotherapy.



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 Dr. Luis Raez, MD FACP FCCP

Chief of Hematology/Oncology and Medical Director, Memorial Cancer Institute
Clinical Associate Professor of Medicine, Florida International University

The FDA recently approved Pembrolizumab in combination with chemotherapy for new patients with stage IV or metastatic non-small cell lung cancer.  This important breakthrough is based on a small study, a randomized phase II study, presented by Merck that basically shows that there is a benefit of adding the immunotherapy agent Pembrolizumab to the conventional chemotherapy carboplatin base.  This is very important because, until three weeks ago, the only way a patient could get immunotherapy in the front line was if he was able to have the PD-L1 marker expression in the tumor more than 50%.  So that was the only approval for immunotherapy as a single agent for new patients.  Since the approval now, the patient not only can have Pembrolizumab but can also have chemotherapy at the same time with the idea to improve response rate and progression-free survival.  So this is a very important landmark approval but it is not based on a phase III randomized study so this approval has to be verified as a condition to a phase III study that is ongoing that needs to be finished and the results presented to see if this combination of Pembrolizumab with chemotherapy is going to be our new standard of care.  That is why it is not embraced by all the doctors yet.  The other important thing to remember is that, in this approval given by the FDA, patients do not have to the 50% staining of their tumors with the marker PD-L1. If you will remember, I said at the beginning, if you want to have Pembrolizumab as a single agent as a new patient, you have to stain more than 50% of your tumor with the PD-L1.  If you are going to use now  Pembrolizumab with chemotherapy we don’t need the stain.  It is approved now for people that have a higher stain of more than 50% and for people who have less stain, less the 49 or 50%.  That is a very important difference.  The other thing is we already have six other immunotherapy agents in development, at least, and we have a lot of expectation waiting to know what is going to happen with the other immunotherapy agents and, hopefully, some of them will be able to be more in the front line. 



Is It Feasible and Clearly Beneficial to Combine Immunotherapy Approaches?




Drs. Leora Horn, Ben Solomon, & Jack West review the potential rationale and possible limitations of combining different immuntherapy strategies with one another.

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Dr. West:  I would say, one of the other really hot concepts at World Lung and various other meetings, is combinations with immunotherapy. And that can be two different immunotherapy agents, perhaps a drug like Yervoy (ipilimumab), which is a CTLA-4 inhibitor, that really targets a different part of the immune system, in combination with these immune checkpoint inhibitors, like PD-L1, PD-1 — or, as we have alluded a bit to, chemotherapy in combination with immunotherapy or targeted therapy. How excited are you by some of the combinations, starting with, say, the different immune therapies combined together — is this incrementally far better than any one of these drugs, and is it financially possible to do this in the world we live in?

Dr. Solomon: So, I think in melanoma, the combination data looks super exciting. I think the combination of ipilimumab and nivolumab looks really impressive, particularly in PD-L1 negative patients, and it has to be a said, even that data are relatively early data. We know that it improves progression-free survival, where we’re yet to find out whether this changes overall survival. In lung cancer, I think Leora probably has been involved in some of the studies, but I’m not sure that we’re at that stage with the data — we’re relatively early, and the early studies were hampered by a lot of toxicity in the patients, and I think at this meeting we saw some slightly different schedules that might have improved the toxicity. Leora?

Dr. West:  Of course, we do need to be mindful that melanoma patients are often quite a bit younger and healthier than your average lung cancer patient. So, what is your thought on this matter?

Dr. Horn:  I agree that the data is very early — the MedImmune with tremelimumab combinations, and the nivolumab and ipilimumab combinations, but the toxicity, I do think, is going to be a big issue for lung cancer patients. They are older, they’re just not as hardy, and the toxicities are not inconsequential when they do happen.

Dr. West:  Yeah, I think that it’s appealing to think that, maybe, combinations will work in a broader range of patients, in whom a single agent may not be enough, and that, hopefully in a few years, we will be able to predict, reliably, which patients are best served by a single drug, versus a combination, if we can find combinations that are tolerable.

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