Lung cancer is characterized by the uncontrolled growth of abnormal cells in one or both of the lungs. The majority of lung cancers begin in the bronchial tubes that conduct air in and out of the lungs. Cancers of the lung are classified by how they appear under a microscope. While there are more than a dozen different kinds of lung cancer, the two main types of lung cancer are non small cell and small cell, which together account for over 90% of all lung cancers. Non small cell lung cancer accounts for approximately 75% of these cancers and consists of squamous cell, adenocarcinoma and large cell types. Small cell lung cancer represents 20-25% of all lung cancers and is also referred to as “oat cell cancer” because of the shape of cells when examined under the microscope.
Diagnosing Lung Cancer
When lung cancer is diagnosed, the doctor must determine the type (small cell or non small cell) and the extent of spread or stage of the cancer in order to determine the best treatment. Lung cancer may grow locally in the lungs or spread distantly (metastasize) to other sites in the body, including lymph nodes, bones, and the brain. Determining the presence of a lung cancer and the type of lung cancer requires examination of tissues from the lung. A biopsy is the removal of a small piece of tissue for examination under a microscope and can be obtained using one or more of the following procedures.
Bronchoscopy: During a bronchoscopy, a surgeon inserts a bronchoscope (thin, lighted tube) through the nose or mouth into the trachea (windpipe) and bronchi (air passages that lead to the lung). Through this tube, the surgeon can examine the inside of the trachea, bronchi and lung and collect cells or small tissue samples.
Fine Needle Aspiration: During this procedure, a surgeon inserts a needle through the chest into the cancer to remove a tissue sample for examination under the microscope.
Thoracentesis: During a thoracentesis, a surgeon uses a needle to remove a sample of the fluid that surrounds the lungs in order to check for the presence of cancer cells.
Thoracotomy: A thoracotomy is a major operation, which involves opening the chest in order to diagnose lung cancer.
Sputum Cytology: Sputum cytology is a procedure used to examine mucus that is coughed up from the lungs or breathing tubes. The mucus is examined under a microscope in order to detect cancer cells.
Personalized Lung Cancer Care & Precision Medicine
Targeted and more-individualized treatment for NSCLC becomes a reality.
Lung cancers used to be diagnosed solely by a visual microscopic examination of tumor tissue and all patients received the same chemotherapy. Now, doctors are personalizing care by finding the genetic alterations within the cancer that drive its growth and use medicines that specifically counteract the cancerous effects of those genes. In addition, these “targeted therapies” are designed to treat only the cancer cells and minimize damage to normal, healthy cells. The ability to test a patients’ cancer for individual differences at the genetic level, and to make treatment decisions based on those differences is the hallmark of precision medicine.
Tailored treatments have emerged to match a person’s genetic makeup or a tumor’s genetic profile. As a result, ALL patients with lung cancer should receive molecular testing for epidermal growth factor receptor (EGFR), the anaplastic lymphoma kinase (ALK) mutation, and the ROS-1 mutation the results of which can guide their physicians in determining which therapies are more likely to be effective. In fact guidelines now recommend molecular testing on a sample of the cancer taken during a biopsy should be considered before deciding upon treatment.1 Results from these tests provide important information about every patient’s cancer so that treatment decisions can be tailored accordingly.
Treatment strategies are individualized based upon the test results to include agents that specifically target each patient’s cancer characteristics to achieve optimal outcomes.
PD-1: PD-1 is a protein that inhibits certain types of immune responses, allowing cancer cells to evade an attack by certain immune cells. Drugs that block the PD-1 pathway enhance the ability of the immune system to fight cancer and are referred to as checkpoint inhibitors for their ability to help the immune system recognize and attack cancer. Overall 66% of lung cancer patients have some expression of PD-1, and 28% are “high expressers” with over 50% of the tested tumor expressing PD-1.1
EGFR: The epidermal growth factor receptor (EGFR) pathway is a normal biologic pathway found in healthy cells. It is involved in regular cellular division and growth. However, certain mutations within the EGFR gene can lead to an overactive EGFR pathway, leading to the development and/or spread of cancer. These cancers are referred to as EGFR-positive, and there are several FDA-approved medications to block the activity of EGFR and slow cancer growth for EGFR-positive cancers. EGFR mutations are most common in people of Asian ethnicity, women, never-smokers, and those with a type of lung cancer known as adenocarcinoma.
FDA-approved medications that block EGFR activity in NSCLC include the following: Each is indicated for different treatment phases of NSCLC, and works via slightly different mechanisms so when one stops working, another may still be useful.1
- Tarceva® (erlotinib)
- Gilotrif® (afatinib)
- Iressa® (gefinitib)
- Tagrisso® (osimertinib)
- Necitumumab® (Portrazza)
ALK+ Lung Cancer: Approximately 5% of all NSCLC have an identified mutation referred to as the anaplastic lymphoma kinase (ALK) mutation. The ALK mutation is responsible for initiating and promoting cancer growth. Individuals with ALK+ lung cancer tend to be non-smokers or former light smokers; younger, and are a type of NSCLC referred to as adenocarcinoma (based upon the cells affected); and respond worse to standard chemotherapy regimens than patients who do not have the ALK mutation.
Recently, agents have been developed to specifically reduce or decrease cellular growth and spread caused by the ALK mutation.
FDA Approved Agents for ALK+- Lung Cancer
- Xalkori® (crizotinib)
- Alcensa® (alectuzumab)
- Zykadia® (ceritinib)
ROS-1+ Lung Cancer: The ROS-1 mutation is an uncommon mutation found in only 1% of individuals with NSCLC. Research has indicated that the ROS-1 mutation plays a role in the development and progression of some lung cancers, and patient characteristics are similar to those who have ALK+ NSCLC.
FDA Approved Agent for ROS-1 Lung Cancer
- Xalkori® (crizotinib)
Staging: Determining the stage or extent of spread of the cancer is essential in order to understand treatment options or interpret published cancer treatment information. Determining the stage of lung cancer may require many tests, which often include the following:
1 OSI Pharmaceuticals. FDA Approves Tarceva as a Maintenance Therapy for Advanced Non-small Cell Lung Cancer. Available at: http://investor.osip.com/releasedetail.cfm?ReleaseID=460783. Accessed April 19, 2010.
2 Zhou C, Wu Y-L, Chen G et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomized, phase 3 study. Lancet Oncology. Early online publication July 22, 2011.
3 Shaw AT, Kim DW, Mehra R, et al: Ceritinib in ALK-rearranged non–small-cell lung cancer. New England Journal of Medicine. 2014; 370: 1189-1197.
4 Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer. New England Journal of Medicine. 2015; 373:1627-1639.