Friday, December 16, 2016

Precision Medicine: Where Are We In Lung Cancer?

Lung cancer is the most common cause of cancer mortality globally, responsible for nearly 1 in 5 cancer-related deaths, or an estimated 1.6 million people. In the U.S., lung cancer is by far the leading cause of cancer-related death among both men and women; more deaths are caused by lung cancer every year than by breast, prostate, and colon cancer combined.  But after years of modest growth in new treatment options, there is much cause for hope. In 2015, the FDA approved six new drugs for the treatment of lung cancer—a one-year record – including two new immunotherapy drugs, nivolumab (Opdivo®) and pembrolizumab (Keytruda®). These approvals were landmark events for the treatment of lung cancer in 2015.

And the scientific evidence is accumulating that genomic testing and targeted therapies for lung cancer patients, particularly those who have advanced, or metastatic non-small cell lung cancer (NSCLC) make a significant difference in outcomes.  The most useful biomarkers for predicting the efficacy of targeted therapy in advanced NSCLC are genomic alterations called "driver mutations”.  Genomic tests for driver mutations have become an increasingly standard part of the diagnostic work-up for NSCLC patients, and the testing is useful in choosing whether a patient receives chemotherapy (if there is not a targetable driver mutation) or an FDA-approved targeted therapy up-front.  The best characterized of these biomarkers are epidermal growth factor receptor (EGFR) mutations and (anaplastic lymphoma kinase) ALK translocation. Identification of these biomarkers has led to highly targeted treatments that have resulted in major advances in prolonging survival - without the harsh side effects of chemotherapy. Patients with specific genetic mutations may benefit from targeted therapies such as the EGFR blockers erlotinib (Tarceva®), afatinib (Gilotrif®), and gefitinib (Iressa®), to name a few.
Lung cancer treatments are advancing so fast that it’s important to get tested to find out if a patient has an identifiable mutation. Patients with advanced NSCLC, and their caregivers need to have the conversation with their care team about getting tested and understand the abnormality that is causing the cancer. If a therapy exists patients are having good outcomes. If there is not a targetable mutation, patients can find clinical trials that may help prolong life. Not every driver has an effective treatment, but according to the LCMC II study nearly 60% of NSCLC adenocarcinoma patients are likely to have a driver gene that can be targeted with approved drugs or those in a clinical trial. This is amazing progress in lung cancer treatment, and made possible by cancer research. The basic research done 10 years ago is leading to breakthroughs today. It’s why I support the vision of the #CancerMoonshot program’s aim “to make a decade worth of advances in cancer prevention, diagnosis and treatment in five years."
A recent article by Dr. Lecia Sequist (Associate Professor of Medicine, Harvard Medical School) and Dr. Joel  Neal (Assistant Professor of Medicine–Oncology, Stanford University/ Stanford Cancer Institute) shares good information about the professional medical organizations that recommend analyzing either the primary NSCLC cancer tumor or a metastatic tumor for EGFR and ALK, regardless of patient characteristics (such as age, race, or smoking history). And The National Comprehensive Cancer Network guidelines for metastatic non-small cell lung cancer strongly recommend testing for alterations in EGFR, ALK, and ROS1 genes, as well a broader genomic panel to look for driver genes that might have clinical trials available. In this shifting landscape in lung cancer treatment, molecular testing may identify a targeted treatment, or help find a clinical trial. Patients need to be their own health care advocates.