GRACE :: Lung Cancer

Immunotherapy

Denise Brock

ASCO 2017 – Lung Cancer – Keytruda is Now Approved in Combination with Chemo for Advanced Non-Squamous NSCLC

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H. Jack West, MD
Medical Director
Thoracic Oncology Program Swedish Cancer Institute
President & CEO, GRACE
Matthew Gubens, MD
Thoracic Oncologist
Thoracic Surgery and Oncology Clinic
UCSF Helen Diller Family Comprehensive Cancer Center
Jyoti D. Patel, MD
Director Thoracic Oncology
University of Chicago Medicine

 

Drs. H. Jack West, Medical Director of the Thoracic Oncology Program at Swedish Cancer Institute in Seattle, Washington and President and CEO of GRACE, Matthew Gubens, Thoracic Oncologist at the Thoracic Surgery and Oncology Clinic of the UCSF Helen Diller Family Comprehensive Center in San Francisco, California, and Jyoti Patel, Director of Thoracic Oncology at University of Chicago Medicine gathered post meeting to discuss new information from ASCO 2017 regarding lung cancer.   In this roundtable video, the doctors discuss Keytruda is Now Approved in Combination with Chemo for Advanced Non-Squamous NSCLC.



 

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Dr West

Why I Don’t Favor an Front-Loaded Approach for Most Advanced NSCLC Patients

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To many, the recent FDA approval of a combination of chemotherapy and concurrent immunotherapy for the vast majority of patients with advanced (metastatic) non-squamous non-small cell lung cancer (NSCLC) probably seems like a great idea. This approval was based on the more favorable results for the combination of the IV immunotherapy agent Keytruda (pembrolizumab) every 3 weeks along with first line carboplatin and Alimta (pemetrexed) as a the chemo backbone, compared to the same chemotherapy alone, in a relatively small randomized trial of 123 patients, called KEYNOTE-021g. The “g” part refers to this actually being just one portion of a much larger trial comparing chemo to the same chemo with Keytruda. The other arms haven’t panned out as favorably.

Importantly, when we talk about the arm of patients getting chemo combined with immunotherapy, we aren’t talking about improving survival. Instead, we’re talking about prolonging the time before patients showed significant progression of their cancer on scans, which leads us to switch to a new treatment. This “progression-free survival”, or PFS, was the primary goal of the trial, though the gold standard of what we should really want from our treatments is improvement in how long patients live. There’s a bit of a favorable trend for that, but that’s all. There was also a significant improvement in the fraction of patients who show major shrinkage of their cancer when Keytruda is added to chemotherapy.

Still, even if survival isn’t improved, the results seem promising enough, so what’s not to like? Continue reading


Denise Brock

Lung Cancer Video Library – Role for Immunotherapy for Patients with Driver Mutations

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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 the Role for Immunotherapy for Patients with Driver Mutations.


 

 

 

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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
 

 

 


  


Denise Brock

Lung Cancer Video Library – Multiple Immunotherapy Agents

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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 Multiple Immunotherapy Agents.


 

 

 

How Did You Like This Video?

Please feel free to offer comments and raise questions in our Discussion Forums.


 

TRANSCRIPTS 
Click to download  (coming soon)
 

 Dr. Luis Raez, MD FACP FCCP

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

 

 


  


Luis E Raez

More Immunotherapy Agents are in Development for Lung Cancer

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Luis E. Raez, MD, FACP, FCCP

Luis E. Raez, MD, FACP, FCCP, Chief of Hematology/Oncology and Medical Director of Memorial Cancer Institute (Miami, FL) Clinical Associate Professor of Medicine, Herbert Wertheim College of Medicine, Florida International University

In the last 2 years we were very happy to have seen: nivolumab, pembrolizumab and recently atezolizumab approved for non-small cell lung cancer (NSCLC). If you remember all of them are approved for second line therapy of NSCLC and pembrolizumab has been moved and approved already for first line NSCLC therapy if the tumor expresses PDL-1 immunohistochemistry staining (IHC) more than 50%. All of these agents block the interaction between the receptor PD-1 present in T lymphocytes and the ligand PDL-1 present in tumor cells and they are called “checkpoint inhibitors”. Some of them like atezolizumab block the PDL-1 ligand and the others are PD-1 inhibitors, there are no clear differences among them other than the current FDA indications. Soon we will know if there are differences in these 2 types of inhibitors among themselves regardless effectivity or toxicity. However these are not the only agents, we have more PDL-1 inhibitors in development like: avelumab (also known as MSB0010718C) that is in priority review for urothelial cancer but results from the JAVELIN trial were recently reported in December in Vienna during the 17th International Association for the Study of Lung Cancer (IASLC) Annual Meeting showing good responses and toxicity profile similar to the other inhibitors. The same happened with another anti-PDL-1 called durvalumab that was also presented at the IASLC meeting too with similar outcomes. But not only anti PD-1/PDL-1 antibodies are considered check point inhibitors we also have to remember that we have anti-CTL4 antibodies called ipilimumab and tremelimumab; none of them are approved for lung cancer yet but the first is already commercially available for melanoma. The importance of these anti-CTL4 antibodies is in the fact that they stimulate the immune response by a different mechanism of the PD-1/PDL-1 inhibitors then the great interest from the research community in combining these 2 different type of drugs to try to enhance the immune response as already has happened successfully in melanoma where the combination of ipilimumab + nivolumab is becoming standard. Other investigators are already combining durvalumab with tremelimumab for NSCLC, the first phase I study was published in the journal “Lancet” in February 2016 where they showed a manageable tolerability profile, with antitumour activity irrespective of PD-L1 status. During World Lung IASLC conference in December 2016 the combination of ipilimumab + nivolumab was presented showing good tolerance for the patients and enhancing the immune response of single agent nivolumab and the final paper was published also in “Lancet” in January 2017.

But this story even gets better: while some pharmaceutical companies are developing similar check point inhibitors to the 2 types described (anti PD-1/PDL-1 and anti-CTL4) other companies are exploring other targets and checkpoints so there is a large list of potential candidates that can be targeted with  the hope to achieve an immune response like: A2AR, B7-H3, also called CD276, B7-H4, also called VTCN1, BTLA also called CD272, IDO, short for Indoleamine 2,3-dioxygenase; KIR, short for Killer-cell Immunoglobulin-like Receptor, LAG3, short for Lymphocyte Activation Gene-3, TIM-3, short for T-cell Immunoglobulin domain and Mucin domain 3, and VISTA (protein), Short for V-domain Ig suppressor of T cell activation, among others.

The future is very exciting these days for the possibilities that is bringing to our NSCLC patients.


 Luis E. Raez, MD, FACP, FCCP is the Chief of Hematology/Oncology and Medical Director at Memorial Cancer Institute. He is also the Oncology Research Director of Memorial Healthcare System and Director of the Thoracic Oncology Program, Clinical Associate Professor of Medicine at Florida International University and Visiting Professor of Medicine at Cayetano Heredia University in Peru. He is also an Affiliate Associate Professor of Clinical Biomedical Science for Florida Atlantic University.


 

 

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