GRACE :: Lung Cancer

Lung Cancer

Denise Brock

Targeted Therapies Patient Forum September 2017 update

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GRACE is excited to continue to build the faculty and agenda for the upcoming Targeted Therapies Patient Forum in September 2017.  See below for our growing list of topics and presenters! 

Targeted Therapies in Lung Cancer Patient Forum
September 16, 2017

Presented by the Global Resource for Advancing Cancer Education in collaboration
with the Cleveland Clinic Cancer Center

Register at cancerGRACE.org | Agenda is subject to change

8:30 – 10:00 am        The Many Faces of Progression
Dr. Nathan Pennell Cleveland Clinic Cancer Center The Role of Local Therapy
Dr. Shirish Gadgeel Karmanos Cancer Center, Wayne State University Biopsies & Re-biopsies
Dr. Karen Reckamp, City of Hope
10:30 – noon       
The Question of Clinical Trials
Dr. Alice Shaw Massachusetts General Hospital The Crossroads: Local Therapy, Chemo, Targeted Therapy, or Immunotherapy? 
Panel Discussion with Drs. Pennell, Gadgeel, Reckamp, and Shaw, and patients Matt Hiznay (ALK) and Sara Whitlock (RET). Moderator: Dr. H. (Jack) West

BREAKOUT SESSIONS

1:00 – 2:30 pm     
 
Presentations by Lung Cancer Sub-type
*Available treatment options 
*Acquired resistance: How do you pick your next treatment? 
ALK/ROS Dr. Alice Shaw, Dr. Shirish Gadgeel, & Matt Hiznay, ALK patient
EGFR Dr. Nathan Pennell, Dr. H. (Jack) West, & John Cherol, EGFR patient
MET/RET/BRAF Dr. Karen Reckamp, Dr. Vamsidhar Velcheti (Cleveland Clinic Cancer Center), & Sara Whitlock, RET patient

BREAKOUT SESSIONS

2:50 – 4:00 pm     
 
Managing the Costs of Cancer Care
James P. Stevenson, MD Cleveland Clinic Cancer Center
Patient to Patient Mentoring
Kathryn Sefcek, MHA 4th Angel Mentoring Program
Avoiding Fake News & Finding Trustworthy Cancer Info Online
Dr. H. (Jack) West Swedish Cancer Institute & Founder of cancerGRACE
Janet Freeman-Daily ROS1 patient, #LCSM Twitter Chat co-moderator, Cure Today contributor, Gray Connections blogger

 


 

Introducing Our Speakers

for full faculty bio’s, please visit our FACULTY page

***Speaker Highlights***

Learn about ALK patient Matt Hiznay in this video; Matt serves on the event’s planning committee and will present during the ALK break-out session.

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

 

 


GRACE would like to thank the following companies for their support of this forum:

B-I for web           
Guardant

 

 


Dr Walko

Translation of Molecular Genetics in Lung Cancer into Treatment Decision

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Christine M. Walko, Pharm.D., BCOP, FCCP, Personalized Medicine Specialist, DeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center, Associate Professor, University of South Florida Morsani College of Medicine, Tampa, Florida

Advancements in technology have improved the quality, cost and turnaround time for assessing genetic mutations in tumor tissue. This has helped to translate precision medicine into standard clinical practice.  Testing for genetic alterations is now a standard part of the work-up for a patient with newly diagnosed advanced lung cancer.  Additionally, since getting a sample of tumor tissue is not always possible, blood can be analyzed for tumor DNA and also provides a mechanism for assessing the genetic make-up of a tumor.  This is especially helpful in lung cancer where getting tumor tissue may be challenging.  We know that cancers grow by increasing “go” signaling, called oncogenes, and decreasing “stop” signals like tumor suppressor genes.  Genetic changes in an oncogene, like epidermal growth factor receptor (EGFR), can cause a tumor to keep growing.  It has been known for many years that activating mutations in EGFR can predict response to drugs that inhibit EGFR, including erlotinib (Tarceva®), gefitinib (Iressa®), afatinib (Gilotrif®) and osimertinib (Tagrisso®).  We also know that other targetable mutations can occur in non-small cell lung cancer (NSCLC) and cause “go” signals through other genes besides EGFR.  These include BRAF activating mutations, MET exon skipping, RET fusions, ERBB2 mutations and others.  These mutations are considered “rare” but with more than 224,000 new cases of lung cancer expected to be diagnosed in 2016, even “rare” mutations can affect several thousands of patients every year.  For example, MET exon 14 mutations are seen in about 3-4% of non-small cell lung cancers but this translates to around 7000 patients each year.

Genetic Mutations Reported in Adenocarcinoma of the Lung and Associated Treatment Options

Below is a brief review of 3 less common alterations as they relate to NSCLC and the evidence supporting drugs directed to these targets.

  1. BRAF activating mutations: BRAF is an oncogene that is most commonly associated with melanoma and activating mutations are seen in about 50% of cutaneous melanomas. Activating mutations in BRAF are seen in up to 7% of NSCLC and typically occur in current or former smokers.  Inhibitors of BRAF, and a protein downstream of BRAF called MEK, have been initially developed in melanoma but are being assessed in other cancer types like NSCLC.  There are 2 BRAF inhibitors approved (dabrafenib (Tafinlar®)and vemurafenib (Zelboraf®) and 2 MEK inhibitors approved (trametinib (Mekinist®) and cobimetinib (Cotellic®).  These drugs are most effective when a BRAF inhibitor is used in combination with a MEK inhibitor. Dabrafenib plus trametinib is the most commonly studied combination in NSCLC.  A phase 2 trial of 59 patients with previously treated NSCLC that was found to have a BRAF activating mutation were treated with this combination of drugs.  An objective response was seen in 63% of patients with 2 patients having a complete response and 34 patients having a partial response in tumor shrinkage.  The median duration of response to the drugs was 9 months.2 
  1. MET exon 14 skipping mutations: MET is an oncogene that can promote cancer growth when it’s consistently turned on.  MET is a receptor for a protein called HGF.  When HGF binds to MET, it turns on MET which causes “go” signals to cancer cells to grow.  The body can regulate these signals by destroying MET when it does not need it to be turned on.  This specific MET alteration prevents MET from being destroyed and keeps it turned on, continuing to send “grow” signals to the cancer cells.  This MET alteration is seen in about 3-4% of NSCLC and is more common in a subtype of NSCLC called “pulmonary sarcomatoid carcinoma”.  Additionally, patients with this MET alteration are usually older (median age of 72 years of age), female, and former or current smokers.3  There are several drugs that can inhibit MET with crizotinib (Xalkori®) being the most commonly investigated in NSCLC.  Crizotinib is a drug that inhibits several different targets in lung cancer and is most commonly used for patients whose cancers have genetic alterations of ROS1 or ALK.  In a small case series of 5 patients with NSCLC who were previously treated with other drugs, 4 patients received crizotinib with 3 of these patients have a partial response and progression free survival of 3.6 months or more (2 patients were still responding after 3.1 and 4.6 months, each).4 
  1. RET activating fusions: RET is an oncogene that can become activated by “fusing” with another gene. This happens when the chromosome where RET is located breaks into 2 pieces and reassembles upside-down.  These alterations are called “fusions” and they are reported by listing both genes, such as KIF53-RET.  This means that the RET gene has been fused to part of the KIF53 gene.  This causes the RET gene to be turned on and signal to cancer cells to grow.  RET fusions are seen in about 1-2% of NSCLC and are more common in younger patients who are never-smokers.  There are several drugs that can inhibit RET with cabozantinib (Cometriq®) and vandetanib (Caprelsa®) being the ones looked at the most in NSCLC.  These drugs are both approved for a type of thyroid cancer. A phase 2 trial of 26 patients with NSCLC who had RET-fusions and who had received prior treatment were given cabozantinib.  A partial response was seen in 28% of patients.  Of these patients, 75% of them had at least a 30% decrease in tumor size within the first 4 weeks of receiving the drug.  The median duration of treatment was 7 months with 4 patients receiving the drug for longer than one year.5  Vandetanib was also assessed in a phase 2 trial of 18 patients with NSCLC who had RET-fusions and who had received prior treatment.  Confirmed tumor responses were seen in 53% of patients and the progression free survival was 4.7 months.6  

These genetic markers are all mentioned in treatment guidelines for NSCLC, however an ongoing question focuses on when to use targeted therapy that has been tested in a smaller group of patients compared with standard chemotherapy or immunotherapy that has been tested in larger numbers of patients.  All of the trials discussed above were small and performed in patients who received prior therapy.  Ongoing studies are trying to help answer this question.  The best answer for each patient depends not only on the genetic tumor results but also other aspects of each patient’s disease and personal characteristics, making discussion with the medical team essential for personalizing therapy.    

References:

  1. Thomas A, et al. Refining the treatment of NSCLC according to histologic and molecular subtypes. Nat Rev Clin Oncol. 2015;12(9):511-526.
  2. Planchard D, et al. Dabrafenib plus trametinib in patients with previously treated BRAF V600E-mutatnt metastatic NSCLC: an open-label, multicenter phase 2 trial. Lancet Oncol. 2016;17(7):984-993.
  3. Awad, MM, et al. MET exon 14 mutations in NSCLC are associated with advanced age and stage-dependent MET genomic amplification and c-MET overexpression.  J Clin Oncol. 2016;34(7):721-730.
  4. Paik, PK, et al. Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring MET mutations causing exon 14 skipping. Cancer Discovery.  2015,5(8):842-849.
  5. Drilon, A, et al. Cabozantinib in patients with advanced RET-rearranged NSCLC: an open-label, single-center, phase 2 single-arm trial. Lancet Oncol. 2016;17:1653-60.
  6. Yoh K, et al. Vandetanib in patients with previously treated RET-rearranged advanced NSCLC (LURET): an open-label multicenter phase 2 trial.  (Lancet Respir Med. 2017;5(1):42-50).

Christine M. Walko, Pharm.D., BCOP, FCCP is a Personalized Medicine Specialist at the DeBartolo Family Personalized Medicine Institute at the H. Lee Moffitt Cancer Center and is also Associate Professor at the University of South Florida Morsani College of Medicine in Tampa, Florida. She is also the Chair of the Clinical Genomics Action Committee (CGAC) and an Attending on the Personalized Medicine Clinical Service at H. Lee Moffitt Cancer Center.  Dr. Walko received her Doctor of Pharmacy from Duquesne University in Pittsburgh. She completed a pharmacy practice residency at Virginia Commonwealth University Health System/Medical College of Virginia Hospitals in Richmond, Virginia. She also completed a Hematology/Oncology specialty residency at the University of North Carolina (UNC) Hospitals and Clinics and a Hematology/Oncology fellowship at the University of North Carolina School of Pharmacy in Chapel Hill, North Carolina. She is a board certified oncology pharmacist.

She has researched and published extensively in oncology therapy and has presented nationally and internationally on oncology, pharmacogenomics, and molecular tumor boards.


 

 

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


 

 

 


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.


 

 

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


 

 

 


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.    
 

Download the Agenda

 
 
 
 
 
 


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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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