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Personalized medicine for lung cancer: Test for the cancer driver and then target it!

Contacts:

Murry W. Wynes, PhD                      
IASLC Special Projects Manager              
Murry.Wynes@IASLC.org               
(720) 325-2945                                

FOR IMMEDIATE RELEASE

Personalized medicine for lung cancer: Test for the cancer driver and then target it!

DENVER – November is Lung Cancer Awareness Month and the International Association for the Study of Lung Cancer (IASLC) is the only global organization solely dedicated to the study of lung cancer and is committed to conquer thoracic malignancies worldwide. Each year 1.6 million individuals are diagnosed with lung cancer globally (US 225,000) and 1.4 million individuals die from the disease (US 160,000). Lung cancer is the leading cause of cancer related deaths throughout the world. In the US, lung cancer is the leading cause of cancer death in both men and women. The majority of cases (~60%) are diagnosed after the disease has spread to distant areas and the 5-year survival rate for those with advanced disease is only around 4%.

Personalized medicine, treating the patient with therapies that are predicted to be effective based on the molecular characteristics of the tumor, can add years of life for those patients whose tumor harbor specific abnormalities and treated with a therapy specifically targeting this abnormality.

Guidelines issued by IASLC, College of American Pathologists (CAP), and Association for Molecular Pathology (AMP) recommend that patients with advanced non-small cell lung cancer (NSCLC) with an adenocarcinoma histology component should be tested for mutations in the epidermal growth factor receptor (EGFR) gene. Patients whose tumors display these mutations respond to EGFR tyrosine kinase inhibitors (TKIs) and have significantly improved prognosis compared to standard chemotherapy. Paul A. Bunn, Jr, MD and former Director of IASLC explains that “a new era in personalized medicine for patients with advanced lung cancer arose with the discovery that mutations in the EGFR gene cause constitutive activation of the receptor, which “drives” the cancer, and that drugs such as erlotinib, gefitinib and afatinib that bind to the receptor produce high response rates and long remissions in patients with these mutations”. Erlotinib and afatinib are approved inhibitors in the United States (US) for metastatic NSCLC with EGFR mutations and gefitinib is also approved in other regions of the world for the same indication. Newer generation EGFR TKIs have been shown to be effective in patients that develop resistance to gefitinib, erlotinib or afatinib by deveolpment of a new EGFR mutation called T790M that reduces binding of the early drugs. Both AZD9291 and rociletinib have received breakthrough therapy designation by the FDA in the US. Dr. Bunn continues, “not only do these oral agents have considerably less toxicity than chemotherapy but they produce prolonged survival that can be increased even further by the third generation drugs when introduced at the time of progression. Thus, patients may live considerably longer on the oral targeted drugs compared to chemotherapy without the severe toxicity.”

IASLC, CAP, and AMP also recommend that patients with advanced NSCLC with an adenocarcinoma histology component should be tested for DNA rearrangement of the anaplastic lymphoma kinase (ALK) gene. ALK positive patients respond to ALK TKIs and have significantly better prognosis compared to other therapies. Crizotinib is an approved inhibitor in many locations throughout the world for metastatic NSCLC positive for ALK rearrangements. Ceritinib, a newer generation ALK inhibitor was recently approved by the FDA in the US because it was shown to be effective in patients with acquired resistance or intolerability to crizotinib. Alectinib and AP26113, other new generation ALK inhibitors, have been granted breakthrough therapy designation.

While the role for EGFR and ALK inhibitors in the treatment of advanced disease is defined, their role in early-stage disease is not. The ALCHEMIST study (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial), initiated by the US National Cancer Institute and launched in August 2014, is designed to evaluate the role of these inhibitors following surgery for early-stage non-squamous NSCLC.

Another ongoing personalized medicine clinical trial, also initiated by the US National Cancer Institute in partnership with the Food and Drug Administration and launched in June 2014, is the Lung Cancer Master Protocol (Lung-MAP) trial for patients with advanced lung squamous cell carcinoma. Patients are screened for genomic alterations and then based on the results of this screening, patients are assigned to one of five sub-studies testing different investigational regimens best suited for their genomic profile and compared to standard chemotherapy. “This is a highly innovative multi-institutional public-private collaborative clinical study,” says Fred R. Hirsch, MD, PhD and Chief Executive Officer of IASLC. “The model of a Master Protocol in lung cancer is expected to rapidly identify active drugs and lead to their approval, which means that active drugs will reach the needed patients much more rapidly than before, thus ultimately improving patient outcomes,” continues Dr. Hirsch.

There are other promising targeted-therapies for potential “molecular drivers” being examined in clinical trials and there will undoubtedly be future recommendations for testing and approved therapies targeting these drivers.

In conclusion Tony Mok, MD and President of IASLC, notes that “EGFR mutations were discovered 10 years ago and first-line EGFR TKI’s were established 6 years ago and now we have a plan to prolong the efficacy of molecularly-targeted therapies at the time of resistance. With that I am optimistic that we will prolong the survival for many lung cancer patients.”

For more information on Lung Cancer Awareness and IASLC please visit us at www.iaslc.org.

 

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About the IASLC:
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated to the study of lung cancer. Founded in 1974, the association’s membership includes more than 4,000 lung cancer specialists in 80 countries. To learn more about IASLC please visit www.iaslc.org

November 3, 2014