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.


 

 

 


Denise Brock

Lung Cancer Video Library – Spanish Language: Video #45 ALK Marker Testing

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GRACE Cancer Video Library - Lung

 

We are pleased to continue this series of informational videos for our Spanish speaking community.  GRACE is pleased to welcome Dr. Rafael Santana-Davila, Assistant Professor with the University of Washington School of Medicine and Seattle Cancer Care Alliance.  In this 45th video for the Spanish lung cancer video library, Dr. Santana-Davila joined GRACE to discuss ALK marker testing. 


 

 

 

How Did You Like This Video?

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


 

TRANSCRIPTS – Spanish and English
download transcripts
 

Prueba de Marcadores Tumorales: Cinasa de Linfoma Anaplásico

ALK Marker Testing

 

Rafael Santana-Davila, MD
Assistant Professor of Medicine
University of Washington Seattle Cancer Care Alliance
Seattle, Washington

 

Spanish TRANSCRIPT

Uno de los principales logros que ha habido en la última década en el tratamiento del cancer de pulmón, es el descubrimiento de que en algunos casos de los casos (alrededor del 10% de los casos en general), se puede descubrir que hay una mutación que es lo que lo ha llevado a que el cáncer se reproduzca fácilmente.

En la mayoría de los casos, esto es una mutación en el gen de crecimiento epidermoide o EGFR. Esto ocurre en alrededor del 10% de los casos de cancer de pulmón general, pero puede llegar a ocurrir en el 50% de los casos de no fumadores.

Hacemos un test en el espécimen de patología y cuando es positivo, el paciente es candidato a tratarse con un medicamento que en la mayoría de los casos es una píldora. Ha habido muchos avances en el tratamiento de este tipo de cancer.

El otro marcador tumoral que buscamos es ALK (cinasa de linfoma anaplásico) que es una translocación en donde lo que pasa es que dos cromosomas intercambiaron información en dos células tumorales llevando a la formación de una nueva proteína. Cuando esto ocurre, el tratamiento está diseñado a atacar esta translocación e inhibir a esta proteína en particular.

Cuando se tiene cualquiera de estos marcadores tumorales, el tratamiento es más específico, por lo que es muy importante saber si el paciente tiene alguno de estos marcadores.


  

English TRANSCRIPT

One of the biggest accomplishments made in the last decade on lung cancer treatment is the discovery that in about 10% of all the patients there is a mutation that is related to the progression of the cancer.

In most cases, it’s a mutation in the epidermal growth factor receptor or EGFR. In general, this appears in about 10% of lung cancer cases, but there can be in 50% of the non-smokers patients. We do a pathology test of the specimen and when it’s positive, the patient is a candidate to receive a special treatment, that is usually a pill. There have been many advances in the treatment of this kind of cancer.

The other tumoral marker we look for is ALK (anaplastic lymphoma kinase), which is a translocation where two chromosomes change information in two tumoral cells and create a new protein. When this happens, the treatment is designed to attack this translocation and inhibit this particular protein.

When the patient has either one of those markers, the treatment becomes more specific. There’s the importance of knowing if the patient has one of them.

 


Denise Brock

Lung Cancer Video Library – Spanish Language: Video #44 Treatment of Stage III Unresectable Non-Small Cell Lung Cancer

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GRACE Cancer Video Library - Lung

 

We are pleased to continue this series of informational videos for our Spanish speaking community.  GRACE is pleased to welcome Dr. Rafael Santana-Davila, Assistant Professor with the University of Washington School of Medicine and Seattle Cancer Care Alliance.  In this 44th video for the Spanish lung cancer video library, Dr. Santana-Davila joined GRACE to discuss the treatment of stage 3 unresectable non-small cell lung cancer.


 

 

 

How Did You Like This Video?

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


 

TRANSCRIPTS – Spanish and English
download transcripts
 

Tratamiento de Cancer de Pulmón de Células no Pequeñas en Estadio Tres no Resecable

Treatment of Stage III Nonresectable Non-Small Cell Lung Cancer

 

Rafael Santana-Davila, MD
Assistant Professor of Medicine
University of Washington Seattle Cancer Care Alliance
Seattle, Washington

 

Spanish TRANSCRIPT

Cuando el paciente se encuentra en estadio tres y no es candidato a cirugía porque el cancer está en varios ganglios del mediastino o por otras razones, lo que hacemos es quimioterapia con radiación al mismo tiempo. La radiación se da todos los días por cuatro a seis semanas y la quimioterapia dependiendo de qué régimen se escoge puede ser una vez por semana o dos ciclos de quimioterapia durante la radiación.

Para saber cuál quimioterapia es mejor es un poco controversial, pero depende mucho de la plática que se tiene con el paciente para conocer el tiempo que se tiene, los beneficios y riesgos. Los regímenes que son más comunes en Estados Unidos son carboplatino con paclitaxel una vez por semana. Una vez que se acaban las cuatro a seis semanas de radiación, se dan otros dos ciclos que se llaman ciclos de consolidación. El otro régimen que es muy común es cisplatino con etopósido y esto se da dos ciclos de quimioterapia durante la radiación sin hacer quimioterapias adicionales.


  

English TRANSCRIPT

When the patient is in stage three and is not a candidate to surgery because the cancer is in some lymph nodes of the mediastinum or other reasons, the best option is chemotherapy with radiation at the same time. The radiation is given every day for four to six weeks and the chemotherapy, depending on the regimen chosen, can be once per week or two cycles of chemotherapy during the entire treatment of radiation.

The types of chemotherapies are controversial because to choose which one is better depends on the discussion you have with your doctor to know the time they have, the risks and benefits. The most common regimens in United States are carboplatin and paclitaxel once per week. Once the four to six weeks are over, two more cycles of radiation are given to consolidate. The other common regimen is cisplatin with etoposide, they are given in two cycles of chemotherapy during the radiation with no additional chemotherapies.


Denise Brock

Lung Cancer Video Library – Spanish Language: Video #43 The Treatment of Early Stage Non-Small Cell Lung Cancer

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GRACE Cancer Video Library - Lung

 

We are pleased to continue this series of informational videos for our Spanish speaking community.  GRACE is pleased to welcome Dr. Rafael Santana-Davila, Assistant Professor with the University of Washington School of Medicine and Seattle Cancer Care Alliance.  In this 43rd video for the Spanish lung cancer video library, Dr. Santana-Davila joined GRACE to discuss  the treatment of early stage non-small cell lung cancer.


 

 

 

How Did You Like This Video?

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


 

TRANSCRIPTS – Spanish and English
download transcripts
 

Tratamiento de Cancer de Células no Pequeñas Cuando Están en un Estadio Temprano

Treatment of Early Stage Non-small Cell Lung Cancer

 

Rafael Santana-Davila, MD
Assistant Professor of Medicine
University of Washington Seattle Cancer Care Alliance
Seattle, Washington

 

Spanish TRANSCRIPT

El cancer de pulmón cuando se encuentra en estadio I o II, el mejor tratamiento es cirugía tratando de quitar el cancer. En la mayoría de las veces, lo que se hace es llevar el paciente a cirugía, quitar el cancer de donde está quitando todo el lóbulo del pulmón y muchos de los ganglios de alrededor. Si los ganglios no están involucrados, el tratamiento es quirúrgico sin ninguno otro tratamiento adicional. Si los ganglios están involucrados, se dará también quimioterapia adyuvante después de la cirugía para erradicar pequeñas células que estén en otros lados del cuerpo. El objetivo del tratamiento es tratar de curar al paciente.

El problema de muchos pacientes es que la cirugía puede ser muy peligrosa porque el pulmón de estos pacientes no es sano y quitar un lóbulo de un pulmón pude ser muy dañino. En estos casos, también se puede tratar con una radiación local. 


  

English TRANSCRIPT

When the lung cancer is in stage one or two, the best treatment is surgery to try to remove the cancer. In most cases, the patient goes into surgery where they eliminate the cancer by removing the lobe of the lung and some of the lymph nodes nearby. If the lymph nodes are not involved, the treatment is only surgical. However, if the lymph nodes are involved, after the surgery the patient has to take adjuvant chemotherapy to eradicate small cells that are in other parts of the body. The main goal is to try to cure the patient.

The problem in some patients is that surgery can be very dangerous because the lung in these patients is not a healthy lung, so by removing its lobe can be quite harmful. In these cases, the treatment can be just local radiation.


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