Non-Small Cell Lung Cancer Treatment
Surgery, radiation, chemotherapy, targeted treatments and immunotherapy—alone or in combination—are used to treat lung cancer. Each of these types of treatments may cause different side effects.
Most stage I and stage II non-small cell lung cancers are treated with surgery to remove the tumor. For this procedure, a surgeon removes the lobe, or section, of the lung containing the tumor.
Some surgeons use video-assisted thoracoscopic surgery (VATS). For this procedure, the surgeon makes a small incision, or cut, in the chest and inserts a tube called a thoracoscope. The thoracoscope has a light and a tiny camera connected to a video monitor so that the surgeon can see inside the chest. A lung lobe can then be removed through the scope, without making a large incision in the chest.
Chemotherapy and Radiation
For people with non-small cell lung tumors that can be surgically removed, evidence suggests that chemotherapy after surgery, known as “adjuvant chemotherapy,” may help prevent the cancer from returning. This is particularly true for patients with stage II and IIIA disease. Questions remain about whether adjuvant chemotherapy applies to other patients and how much they benefit.
For people with stage III lung cancer that cannot be removed surgically, doctors typically recommend chemotherapy in combination with definitive (high-dose) radiation treatments. In stage IV lung cancer, chemotherapy is typically the main treatment. In stage IV patients, radiation is used only for palliation of symptoms.
The chemotherapy treatment plan for lung cancer often consists of a combination of drugs. Among the drugs most commonly used are cisplatin (Platinol) or carboplatin (Paraplatin) plus docetaxel (Taxotere), gemcitabine (Gemzar), paclitaxel (Taxol and others), vinorelbine (Navelbine and others), or pemetrexed (Alimta).
There are times when these treatments may not work. Or, after these drugs work for a while, the lung cancer may come back. In such cases, doctors often prescribe a second course of drug treatment referred to as second-line chemotherapy.
Recently, the concept of maintenance chemotherapy has been tested in clinical trials, either as a switch to another drug before the cancer progresses; or to continue one of the drugs used initially for a longer period of time. Both of these strategies have shown advantages in selected patients.
Chemotherapy Before Other Treatments (Neoadjuvant Treatment)
Receiving chemotherapy before radiation or surgery may help people with lung cancer by shrinking the tumor enough to make it easier to remove with surgery, increasing the effectiveness of radiation and destroying hidden cancer cells at the earliest possible time.
If a tumor doesn’t shrink with chemotherapy, the medication can be stopped right away, allowing the doctor to try a different treatment. In addition, research shows that people with lung cancer are much more able to cope with the side effects of chemotherapy when it is given before surgery.
Sometimes, a short trial period of treatment with the drug shrinks the tumor before surgery. If that is the case, then continued treatment with the same drug after surgery is more likely to benefit the patient. Because many lung cancer specialists around the world are giving chemotherapy to their patients before surgery, patients should discuss it with their doctor.
One of the most exciting developments in lung cancer medicine is the introduction of targeted treatments. Unlike chemotherapy drugs, which cannot tell the difference between normal cells and cancer cells, targeted therapies are designed specifically to attack cancer cells by attaching to or blocking targets that appear on the surfaces of those cells. People who have advanced lung cancer with certain molecular biomarkers may receive treatment with a targeted drug alone or in combination with chemotherapy. These treatments for lung cancer include:
Erlotinib (Tarceva and others). A targeted treatment called erlotinib has been shown to benefit some people with non-small cell lung cancer. This drug blocks a specific kind of receptor on the cell surface—the epidermal growth factor receptor (EGFR). Receptors such as EGFR act as doorways by allowing substances in that they can encourage a cancer cell to grow and spread. Lung cancer cells that have a mutation on the EGFR are likely to respond to treatment with erlotinib instead of chemotherapy. For patients who have received chemotherapy, and are in need of additional treatment, erlotinib can be used even without the presence of the mutation.
Afatinib (Gilotrif). In 2013, the FDA approved afatinib for the initial treatment of metastatic NSCLC in patients with the same EGRF gene mutations or deletions as those who can be treated successfully with erlotinib.
Gefitinib (Iressa). In 2015, the FDA approved gefitinib for the first-line treatment of patients with NSCLC whose tumors harbor specific types of EGFR gene mutations, as detected by an FDA-approved test.
Bevacizumab (Avastin). Just like normal tissues, tumors need a blood supply to survive. Blood vessels grow in several ways. One way is through the presence of a substance called vascular endothelial growth factor (VEGF). This substance stimulates blood vessels to penetrate tumors and supply oxygen, minerals, and other nutrients to feed the tumor. When tumors spread throughout the body, they release VEGF to create new blood vessels.
Bevacizumab works by stopping VEGF from stimulating the growth of new blood vessels. (Because normal tissues have an established blood supply, they are not affected by the drug.) When combined with chemotherapy, bevacizumab has been shown to improve survival in people with certain types of non-small lung cancer, such as adenocarcinoma and large cell carcinoma.
Crizotinib (Xalkori). A treatment that has shown benefits for people with advanced non–small cell lung cancer who have the ALK gene mutation. Crizotinib works by blocking ALK and stopping the growth of the tumor.
Ceritinib (Zykadia). This was approved in 2014 for people with metastatic ALK-positive lung cancer who cannot tolerate crizotinib or whose cancer continued to grow while being treated with crizotinib.
Because the genes of cancer cells can evolve, some tumors may become resistant to a targeted treatment. Medications to meet those challenges are being studied now in clinical trials, which often offer important treatment options for people with lung cancer.
Immunotherapy has recently emerged as a new treatment option for certain lung cancers. While any cancer treatment can cause side effects, immunotherapy is generally well-tolerated; this is in part due to its mechanism of action.
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.
In March 2015, the FDA approved the immunotherapy nivolumab (Opdivo) for the treatment of metastatic squamous NSCLC which was unsuccessfully treated with chemotherapy. Nivolumab works by interfering with a molecular “brake” known as PD-1 that prevents the body’s immune system from attacking tumors.
In 2016, the FDA approved a new immunotherapy called pembrolizumab (Keytruda) for the treatment of advanced NSCLC as an initial therapy. Its therapeutic activity is similar to that of nivolumab. Patients are tested for a protein known as PDL-1 and if a sufficient quantity is identified they may qualify for this treatment.
Additional approaches to immunotherapy for lung cancer have shown promise in early clinical trials and are now in late-phase development. Treatments for NSCLC have advanced the furthest; however, a number of new immune-based treatments for SCLC are also in clinical development. These treatments fall into four main categories:
- Monoclonal antibodies are lab-generated molecules that target specific tumor antigens (a substance that the immune system sees as being foreign or dangerous).
- Checkpoint inhibitors target molecules that serve as checks and balances in the regulation of immune responses.
- Therapeutic vaccines target shared or tumor-specific antigens.
- Adoptive T-cell transfer is an approach in which T-cells (a type of white blood cell) are removed from the patient, genetically modified or treated with chemicals to enhance their activity, and re-introduced into the patient with the goal of improving the immune system’s anticancer response.