Join Leora Horn, MD, MSc, FRCPC and Christine Lovly, MD, PhD as they present their multidisciplinary expertise on a range of cases pertaining to biomarker driven advanced disease lung cancer.

The NCCN Guidelines recommend a multidisciplinary approach for patients with NSCLC so that treatment can be tailored for individual patients, which will improve outcomes by decreasing toxicity and increasing quality of life. Before recommending therapy, it is essential to determine both the histology of the tumor and whether the patient has specific genetic alterations, such as sensitizing EGFR mutations or ALK rearrangements. NSCLC is typically divided into two categories: nonsquamous (which is the most common) and squamous cell carcinomas. For nonsquamous, adenocarcinoma is the most common histology. If the subtype is not clear, it is referred to as NSCLC not otherwise specified (NOS); ideally the subtype should be determined.  Currently, most available targeted therapies outside of a clinical trial are only appropriate for patients with non-squamous NSCLC or NSCLC NOS who have specific genetic alterations.  In patients with advanced adenocarcinoma who have specific genetic alterations, recent randomized trials have shown that targeted therapy improves outcomes by decreasing dyspnea, pain, and cough when compared with chemotherapy. For patients without genetic alterations, systemic chemotherapy is recommended.

It is essential to perform biomarker testing for genetic alterations (i.e., molecular testing) for patients with advanced non-squamous NSCLC to identify which treatment will be most effective for individual patients. Molecular testing may considered in select patients with squamous cell carcinoma if the initial histology was done on a small sample and therefore may not be pure squamous cell carcinoma or if patients  have never smoked. Genotyping driver mutations may change therapeutic decisions for many patients. Molecular testing for EGFR sensitizing mutations and ALK gene rearrangements is recommended in the NCCN Guidelines. The different biomarkers and assays are described in the NCCN Biomarkers Compendium. Many different biomarker screening assays are available including systems that can determine more than 100 genetic alterations at one time (eg, multiplex mutation screening assays, next-generation sequencing [multiplex/NGS]). Conventional screening assays are available and some have been approved by the FDA (e.g., FISH assays to detect ALK gene rearrangements). Multiplex/NGS systems may provide the most information if only small biopsy specimens or cytology samples are available for testing. NGS technology holds great promise for pharmacogenomics; an NGS system was recently approved by the FDA. Oncologists and pathologists need to be familiar with the latest information about pharmacogenomics so they can select the most appropriate testing systems and therapy for their patients.

Patient Considerations -- Advances in histology, molecular diagnostic studies, and targeted therapy are transforming the management of NSCLC. Recent advances permit the rational development of treatment plans and use of multimodality therapy based on the specific characteristics of patient’s tumors (i.e., individualized therapy). In patients with local lung cancer, treatment decisions are made based on the location of the tumor. In advanced disease, clinicians must know whether patients are candidates for targeted therapy by testing tumor tissue to see if certain mutations are present prior to deciding on a treatment for the patient. Patient and physician discussions should include the importance of obtaining a biopsy and the size of the tissue sample for the expected testing requirements. Patients should also be aware that if their tumor contains certain mutations, they may be eligible for targeted therapy.