GRACE :: Lung Cancer

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Denise Brock

Lung Cancer Video Library – SCLC – Novel Therapies In Small Cell Lung Cancer (SCLC): Lurbinectedin

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GRACE Cancer Video Library - Lung

 

H. Jack West, MD
President & CEO, GRACE

 

We are pleased to have GRACE’s Jack West, MD, Medical Director, Thoracic Oncology Program, Swedish Cancer Institute in Seattle, Washington, and President and CEO of GRACE bring 2017 updates to our Lung Cancer Video Library.  

In this latest video, Dr. West discusses exciting new advances in SCLC –  Novel Therapies In Small Cell Lung Cancer (SCLC): Lurbinectedin.  

 


 

 

 

 

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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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Dr West

Imprecision Medicine: Why Keytruda (Pembrolizumab) + Chemo for PD-L1+ NSCLC isn’t Ready for Prime Time

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Let me start by saying that I’m a fan of the immune checkpoint inhibitor Keytruda (pembrolizumab) and consider it the new standard of care as a single agent (monotherapy) first line treatment for the subset of about 28-30% of patients with advanced NSCLC, either squamous or non-squamous, whose cancers have high level expression of PD-L1, defined as 50% or more cancer cells staining on the companion test for Keytruda (an antibody called 22c3).  It can lead to some terrific and long-lasting responses, but it works well only in a minority of patients; in fact, even in the cherry-picked population of patients with cancers that show high PD-L1 expression, the response rate is a little less than 50%, and it’s below 20% in patients with low or no PD-L1 expression. Merck just announced that the FDA has accepted a “supplemental Biologics License Application” (sBLA) that would broaden the FDA approval for Keytruda in NSCLC to all non-squamous NSCLC patients without an EGFR mutation or ALK rearrangement and without regard to PD-L1 expression, giving Keytruda in combination with chemotherapy (carboplatin and Alimta (pemetrexed)).  I think the evidence we have with this combination is encouraging and worthy of further study, but it shouldn’t be enough to lead to broad use as requested in the FDA filing. I think it’s a premature money grab that isn’t necessarily better for patients and is definitely bad for broad society. Let me explain why.

The evidence behind this strategy is from a cohort of patients (cohort G) from a larger study, KEYNOTE-021) of patients randomized to various chemo combinations with or without Keytruda. This particular trial did not have a threshold requirement for PD-L1 and enrolled 123 patients with a good performance status and advanced NSCLC to receive either carboplatin/Alimta alone or the same chemo with Keytruda at a fixed dose of 200 mg IV every 3 weeks. Patients who hadn’t progressed after 4 cycles would continue to receive maintenance Alimta (for the chemo only arm) or Alimta/Keytruda (for the chemo/immunotherapy arm) until progression or prohibitive side effects.

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Denise Brock

Not Your Father’s Squamous Lung Cancer – Supportive Care for Patients

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 Presented by the
Global Resource for Advancing Cancer Education
in collaboration with 
UNC Lineberger and the Lung Cancer Initiative of North Carolina
             

 
On Friday, November 4th, 2016, in collaboration with the UNC Lineberger and the Lung Cancer Initiative of North Carolina, GRACE presented ‘Not Your Father’s Squamous Lung Cancer’, webcast live in Chapel Hill, North Carolina.  Our fourth and final presentation discusses supportive care for patients, including pain management, drug side effects, anorexia and shortness of breath, with Amber Procter, PharmD, and Jason Akulian, MD, MPH.    
 

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We would like to thank the following companies for their support of this program:
 
  
  
 

Denise Brock

Not Your Father’s Squamous Lung Cancer – Future Directions in Treatment

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 Presented by the
Global Resource for Advancing Cancer Education
in collaboration with 
UNC Lineberger and the Lung Cancer Initiative of North Carolina
             

 
On Friday, November 4th, 2016, in collaboration with the UNC Lineberger and the Lung Cancer Initiative of North Carolina, GRACE presented ‘Not Your Father’s Squamous Lung Cancer’, webcast live in Chapel Hill, North Carolina.  Our third presentation discusses future directions in treatment, with Chad Pecot, MD.  

Download the Agenda

 
 
 
 


How Did You Like This Video?

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

 

We would like to thank the following companies for their support of this program:
 
  
  
 

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