Surgery, sometimes in combination with chemotherapy, is the most common treatment option for tumors confined to the lung. Advances in surgical techniques allow doctors to make much smaller incisions to remove tumors or sections of a lung affected by cancer. Using video-assisted thoracoscopic surgery (VATS), the surgeon inserts a tube called a thoracoscope into the chest. This device has a light and a tiny camera connected to a video monitor.
In cases where surgery is not possible, radiation therapy is sometimes used, either alone or in combination with chemotherapy. Radiation may also be used before surgery to shrink the tumor or after surgery to help prevent the cancer from recurring (coming back).
“External beam” radiation is commonly used in treating lung cancer. Standard external beam radiation uses a machine that directs a beam (or multiple beams) of radiation to the tumor. The use of CT (computerized tomography), MRI (magnetic resonance imaging) and PET (positron emission tomography) scans allows radiation oncologists to accurately target tumors, shaping the radiation beams to the size and dimensions of the tumor to help spare healthy tissue.
A newer form of radiation called SBRT (stereotactic body radiation therapy) is sometimes used in the treatment of early-stage lung cancer or lung cancer that has spread to only one site (or a small number of sites). SBRT delivers higher doses of radiation to a small area over a shorter period of time, which kills more cancer cells and minimizes the impact on healthy tissue. For early-stage lung cancer, SBRT has been shown to be beneficial with survival rates that are close to those expected with surgery. Research is ongoing to determine which people with early-stage lung cancer could best benefit from this type of focused radiation as an alternative to surgery.
Another form of radiation therapy uses streams of protons (tiny positively-charged particles located at the center of atoms) to kill tumor cells. With proton beam radiation therapy, precise doses of protons can be delivered to the exact location of the tumor. Recent research has shown that this type of radiation is a viable treatment option for people whose lung cancer has not spread outside of the lung area.
Enhanced technologies, such as image-guided radiation therapy (IGRT) and intensity modulated radiation therapy (IMRT), may be used to help radiation oncologists treat lung cancers with greater precision.
Chemotherapy has long been an effective treatment for lung cancer. It is extremely effective in treating SCLC, and is also used to treat many cases of NSCLC. Chemotherapy can also be helpful for people with early stage cancers that have been (or will be) removed by surgery, and in combination with radiation for locally advanced cancer. It is also an important part of treatment for most people with advanced stage lung cancer.
Chemotherapy drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of lung cancer include:
• Cisplatin (Platinol) and Carboplatin (Paraplatin). These platinum-based drugs are the most common chemotherapies used in treating lung cancer. Most chemotherapy treatment approaches include either cisplatin or carboplatin in combination with another chemotherapy drug.
• Pemetrexed (Alimta). Pemetrexed is used in combination with cisplatin for the initial treatment of advanced non-squamous NSCLC. Pemetrexed is also approved for use alone to treat advanced non-squamous NSCLC after another chemotherapy has been given. In January 2019, the FDA expanded the approval of pemetrexed to include its use with platinum-based chemotherapy and the immunotherapy pembrolizumab for the initial treatment of advanced non-squamous NSCLC that is not caused by a gene mutation.
• Gemcitabine (Gemzar). Gemcitabine is used to treat NSCLC, either in combination with cisplatin or carboplatin as an initial treatment or as a single drug after another chemotherapy has been given.
• Paclitaxel (Taxol), nab-paclitaxel (Abraxane), docetaxel (Taxotere). These drugs are forms of “taxane” chemotherapy and can be given in combination with cisplatin or carboplatin for all types of NSCLC. Docetaxel is frequently given alone or in combination with ramucirumab as a later line of therapy in advanced stage lung cancer. (See the section entitled “Cutting off the blood supply to tumors” for information on ramucirumab.)
• Etoposide (Etopophos, Vepesid). Etoposide is used in combination with other cancer medications for the treatment of SCLC.
Targeted therapies are designed to target the specific cell mechanisms that are important for the growth and survival of tumor cells.
Researchers have discovered that mutations in a gene called epidermal growth factor receptor (EGFR) can cause the development, growth and spread of lung cancer. Approximately ten percent of people with lung cancer have EGFR mutations present in their tumors. EGFR inhibitors—targeted therapies given in pill form—are often used to treat this type of lung cancer. Today, five medications are approved treatment options in the United States for lung cancer that has this gene mutation:
• Erlotinib (Tarceva and others). In 2004, the FDA approved the use of erlotinib for the treatment of NSCLC. In 2013, the approval was expanded as an initial treatment for people with NSCLC that has spread to other parts of the body and has certain types of EGFR mutations, or has a piece missing (called a “deletion”) from the EGFR gene.
• Afatinib (Gilotrif). In 2013, the FDA approved afatinib for the initial treatment of metastatic NSCLC in people with the same EGFR gene mutations or deletions as those treated with erlotinib. In 2018, the FDA expanded its approval to include the treatment of lung cancers with less common EGFR mutations.
• Gefitinib (Iressa). In 2015, the FDA approved gefitinib for the initial treatment of people with NSCLC whose tumors harbor specific types of EGFR gene mutations, as detected by an FDA-approved test.
• Osimertinib (Tagrisso). In 2016, the FDA approved osimertinib for the treatment of people with NSCLC whose tumors have specific EGFR gene mutations and have started to regrow after treatment with erlotinib, afatinib or gefitinib. In 2018, the FDA approved the use of osimertinib as a first-line treatment for people with metastatic NSCLC that harbors common EGFR mutations.
• Dacomitinib (Vizimpro). After a priority review, the FDA approved dacomitinib in September 2018 as an initial treatment for NSCLC with certain EGFR gene mutations as detected by an FDA-approved test.
Another genetic change found in some lung cancers is referred to as ALK fusion or rearrangement. Five targeted therapies are approved by the FDA as treatment options for people whose cancer has this genetic change. These drugs are designed to block the rearranged ALK gene, stopping the growth of the tumor.
• Crizotinib (Xalkori). Crizotinib was approved by the FDA in 2013 for the treatment of metastatic NSCLC tumors with the ALK gene fusion. Additionally, crizotinib was approved in 2016 to treat people with metastatic NSCLC that has a fusion of the ROS-1 gene.
• Ceritinib (Zykadia). Ceritinib was approved in 2014 for the treatment of people with metastatic ALK-positive lung cancer who cannot tolerate crizotinib or whose cancer continued to grow while being treated with crizotinib. In 2017, it was approved for the treatment of newly-diagnosed ALK-positive lung cancer.
• Alectinib (Alcensa). Alectinib was approved in 2015 for people with ALK-positive lung cancer who had already been treated with crizotinib. In 2017 alectinib was approved to be given as a first-line treatment option.
• Brigatinib (Alunbrig). In 2017, brigatinib was approved for the treatment of ALK-positive lung cancer that was previously treated with crizotinib.
• Lorlatinib (Lorbrena). In November 2018, lorlatinib was approved for the treatment of ALK-positive metastatic NSCLC that progressed while being treated with crizotinib or another ALK inhibitor.
In 2017, the FDA approved the targeted therapies dabrafenib and trametinib, administered in combination, for people with NSCLC that has a mutation of the BRAF V600E gene as detected by an FDA-approved test.
There are other gene mutations seen in NSCLC for which targeted therapy options may be available. As most gene mutations tend to be more common in the adenocarcinoma type of NSCLC, it is important that people with adenocarcinoma discuss the value of genetic testing with their oncologist.
Because the genes of cancer cells can evolve, some tumors may become resistant to being treated with a targeted therapy. Medications to meet those challenges are being studied in clinical trials.
Our immune system is constantly working to keep us healthy. It recognizes and fights against danger, such as infections, viruses and growing cancer cells. In general terms, immunotherapy uses our own immune system as a treatment against cancer.
The following immunotherapies have been approved for the treatment of lung cancer in specific situations:
• Nivolumab (Opdivo). In 2015, the FDA approved nivolumab for the treatment of metastatic squamous NSCLC that was unsuccessfully treated with chemotherapy. In the same year, the indication was expanded to include treatment of non-squamous NSCLC after unsuccessful chemotherapy. Nivolumab, an immune checkpoint inhibitor, works by releasing a molecular “brake” known as PD-L1 that prevents the body’s immune system from attacking tumors.
• Pembrolizumab (Keytruda). Initially approved by the FDA in 2015 for PD-L1 positive metastatic NSCLC in the second-line setting, this drug belongs to the same category of drugs as nivolumab. After several expansions of its approval, as of April 2019 it is the only drug in this category approved for the first-line treatment of NSCLC, either alone for treatment of PD-L1 positive tumors, or in combination with chemotherapy regardless of PD-L1 status.
• Atezolizumab (Tecentriq). Approved by the FDA in 2016, atezolizumab is another immune checkpoint inhibitor for the treatment of metastatic NSCLC after failure of chemotherapy. In December 2018, the FDA expanded its approval, in combination with the chemotherapy regimen of bevacizumab, paclitaxel and carboplatin, for previously untreated SCLC that has spread beyond the lung.
• Durvalumab (Imfinzi). In February 2018, the FDA approved durvalumab for the treatment of locally advanced NSCLC after treatment with chemotherapy and radiation.
Cutting Off the Blood Supply to Tumors
Another approach to destroying cancer cells is cutting off the blood supply that tumors need to grow.
Blood vessels grow in several ways, but the process depends on the presence of a substance called vascular endothelial growth factor (VEGF) that can be produced both by both tumors and normal cells. This substance can stimulate blood vessels to penetrate tumors and supply them with the oxygen, minerals and other nutrients that feed their growth.
Bevacizumab (Avastin), a monoclonal antibody, works by stopping VEGF from stimulating the growth of new blood vessels. When combined with chemotherapy, bevacizumab has been shown to effectively shrink tumors in adenocarcinoma (the most common type of NSCLC).
Ramucirumab (Cyramza), also a monoclonal antibody, targets VEGF receptors to help stop the formation of new blood vessels. Ramucirumab is most often given with the chemotherapy docetaxel as a later line of therapy in the treatment of NSCLC, after another treatment stops working.