Molecular Testing In Lung Cancer

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. In recent years, the diagnostic work up and therapeutic options have completely evolved in non-small cell lung cancer. Molecular testing is currently performed before selecting the therapy.

If the EGFR (epidermal growth factor receptor) mutation is present the FDA approved a class of drugs called tyrosine kinase inhibitors (erlotinib, afatinib, gefitinib, osimertinib). This class of drugs in randomized trials was shown to be more effective than chemotherapy as far as disease free survival, overall survival, and less toxic. The most common side effects have been rash and diarrhea.

If the ALK mutation is positive (anaplastic lymphoma receptor tyrosine kinase). The class of drugs effective is ALK inhibitors (crizotinib, alectinib and certinib) small molecule inhibitors of the tyrosine kinase ALK. Only ~ 5% of all NSCLC are ALK positive. This patient population is usually younger non-smokers. The response rate with ALK inhibitors is ~ 60% and the two year survival rate is greater than 50%. The most common side effects included visual disturbance, elevated liver function test and gastrointestinal side effects, in general these drugs were tolerated much better than chemotherapy.

Emerging treatments not yet FDA approved are the HER 2 NEU inhibitor, a monoclonal antibody called Herceptin. HER2NEU mutation is present only in 2% of lung cancers.

Also, the BRAF inhibitors (dabrafinib, trametinib, bemurafenib) are currently being studied in clinical trials.

Molecular profiling has revolutionized the therapy for non-small cell lung cancer.