Lung Cancer

Advances in Treatment Offer Hope to Many People

In the past decade, treating lung cancer has changed as a result of newly approved therapies. Some of the biggest advances come in the form of immunotherapy, molecular therapy and targeted therapy. Immunotherapy harnesses the power of the immune system, molecular therapy targets enzymes known as tyrosine kinases, and targeted therapy allows doctors to give medicines that target specific genes or proteins. These new options may result in longer progression-free disease and a better quality of life.

Lung cancer is one of the first cancer types to embrace the use of precision medicine, which can target a patient’s specific tumor type based on the presence of genetic abnormalities. Research has discovered biomarkers that can be tested to find these abnormalities.

Biomarkers are substances that can be tested in the blood, urine or tissue. They can indicate the possibility of cancer or can be used to measure a response to treatment. Testing for biomarkers is becoming more common as scientists find new biomarkers through their research.

Now that more treatment options are available, it’s important to understand the basics of each so you can discuss them with your health care team.

A first-line therapy is the first treatment given for a disease. When used by itself, first-line therapy is the one accepted as the best treatment. Second-line therapy is given when the first-line therapy doesn’t work or stops working. The following therapies may be used alone or in combination.

Surgery

Surgery is typically the primary treatment for early-stage (Stages I, II and some IIIA) lung tumors. Ideally, a board-certified thoracic surgeon experienced in lung cancer should determine whether the tumor(s) can be successfully removed. The procedure selected will depend on how much of your lung is affected, tumor size and location and your overall health.

  • Wedge resection removes the tumor with a triangular piece of a lobe of the lung.
  • Segmental resection (segmentectomy) removes a larger section of a lobe.
  • Lobectomy removes one of the lungs’ five lobes.
  • Pneumonectomy removes an entire lung.
  • Sleeve resection (sleeve lobectomy) removes part of the bronchus (main airway) or pulmonary artery to the lung along with one lobe to save other portions of the lung.

Any of these types of resection may be done by open thoracotomy (a large incision in the chest wall that requires separation of the ribs) or by less invasive procedures, such as video-assisted thoracoscopic surgery (VATS) with or without robotic surgery. These are performed as the doctor makes small incisions and inserts scopes through the small incisions. These VATS procedures may help preserve muscles and nerves, reduce complications and shorten recovery time.

Some early-stage tumors may be removed with robotic surgery. Special equipment provides a three-dimensional view inside the body while the surgeon guides a robotic arm and high-precision tools that can bend and rotate much more than the human wrist. Finding a surgeon with extensive training and experience in robotic surgery is highly recommended.

Chemotherapy

Chemotherapy is a systemic drug therapy that is typically part of the treatment plan for most stages of NSCLC and is the primary treatment for all stages of SCLC (see Figure 1).

It may be given alone or in combination with surgery, radiation or immunotherapy. In early stages, it may be used before surgery (neoadjuvant) to help shrink the tumor, after surgery (adjuvant) to kill remaining cells, as maintenance therapy following standard chemotherapy or as palliative care to help relieve symptoms.

Your doctor will determine the best therapy for you based primarily on the type of cancer you have. For example, certain chemotherapy drugs may be more effective than others for squamous cell lung cancer.

You may receive chemotherapy in the form of pills to take at home or as a solution injected intravenously (IV) through a vein in your arm or hand or a port in your chest. Treatments may take place at your doctor’s office or an outpatient cancer center. Medication to prevent side effects and additional fluids are usually given with IV chemotherapy in a treatment that may take anywhere from 30 minutes to three hours.

Treatment plans vary but generally follow 21- or 28-day cycles for four to six cycles. A rest period follows each cycle to allow your body to recover. Discuss scheduling options with your treatment team.

Your doctor will monitor the effectiveness of your treatment during periodic appointments for physical exams and imaging. Chemotherapy is usually stopped when the tumor is no longer shrinking, at which point maintenance chemotherapy may be an option to consider.

Immunotherapy

Immunotherapy works by stimulating the patient’s immune system to find and fight cancer. It is systemic and may be used alone or with chemotherapy. It is standard first-line therapy for Stage IV NSCLC without specific molecular alterations. It is standard after chemotherapy and radiotherapy for unresectable Stage III NSCLC and is standard with chemotherapy for extensive-stage SCLC. The type of immunotherapy approved to treat NSCLC and SCLC is immune checkpoint inhibitors. These drugs prevent the immune system from slowing down by using antibodies that bind to proteins on cancer cells. This allows the immune system to keep up its fight against the cancer.

Checkpoints keep the immune system “in check,” preventing an attack on normal cells by using regulatory T-cells. When the correct proteins and cell receptors connect, a series of signals is sent to the immune system to slow down once an immune response is finished.

Two checkpoint receptors that slow down the immune system have been identified for their roles in lung cancer treatment.

  • PD-1 (programmed cell death protein 1) is a receptor involved with telling T-cells to die and to reduce the death of regulatory T-cells (suppressor T-cells). Both slow down an immune response. PD-1 can tell the immune system to slow down only if it connects with PD-L1.
  • PD-L1 (programmed death-ligand 1) is a protein that, when combined with PD-1, sends a signal to reduce the production of T-cells and enable more T-cells to die.

When PD-1 (the receptor) and PD-L1 (the protein) combine, the reaction signals it’s time to slow down.

One of the ways cancer cells can outsmart the immune system is by producing PD-L1 and using it as camouflage so that T-cells will see them as normal cells. T-cells expect only normal cells to produce PD-L1, so when a T-cell encounters PD-L1 on a cancer cell, it is tricked into signaling the immune system to slow down. This is how cancer can hide from the immune system.

The goal of immune checkpoint inhibitors is to prevent PD-1 and PD-L1 from connecting so that the immune system does not slow down. These drugs prevent these connections by targeting and blocking PD-1 or PD-L1, and the immune cells continue fighting the cancer.

This treatment is given by IV only. Your doctor will determine your dosing schedule.

Molecular Therapy

Molecular therapy targets a specific molecular (genetic) abnormality in a tumor. This systemic personalized treatment focuses on certain parts of cells and the signals that cause cancer to grow or keep from dying. These signals are often sent by proteins called tyrosine kinases, which are enzymes involved in many cell functions, including cell signaling, growth and division.

Three main types of NSCLC are driven by certain abnormalities that activate the related tyrosine kinases. Oral drugs called tyrosine kinase inhibitors (TKIs) have been developed for epidermal growth factor receptor (EGFR) abnormalities, anaplastic lymphoma kinase (ALK) rearrangements, neurotrophic receptor tyrosine kinase (NTRK) fusions, ROS1 fusions, MET exon 14 skipping mutations, RET fusion-positive alterations and certain BRAF mutations.

TKIs for other molecular abnormalities are currently under investigation. If your tumor contains a known abnormality, this therapy may be recommended as a first-line treatment for NSCLC.

More than one molecular therapy drug has been developed, so if the first one isn’t effective, another one may be considered.

To determine if you’re a candidate for this type of therapy, sample tissue from your tumor must be tested at a specialized lab to find out if any known molecular biomarkers are present in the cancer cells. Ask your doctor if tissue from a previous biopsy can be used. This should be done before your treatment begins.

If you are diagnosed with NSCLC and your tumor is found to contain a known abnormality, molecular therapy may be recommended as a first-line treatment. In such cases, it has been associated with higher response rates, longer-lasting benefits and far fewer side effects than chemotherapy.

It’s important to understand that many tumors do not test positive for biomarkers for which approved therapies currently exist. However, clinical trials are underway to find effective treatments for additional genetic abnormalities, including KRAS (the most common abnormality), MET, RET, HER2 and others. If your tumor tested positive for one of these biomarkers, ask your doctor if you may be eligible to participate in a clinical trial. Researchers are continuing to identify new biomarkers for lung cancer so additional treatments can be developed.

Radiation Therapy

Radiation therapy is used to kill cancer cells, stop their growth or shrink the tumor. It is often combined with other therapies and may be used as palliative care to help relieve pain when cancer has spread to the bone.

External-beam radiation therapy (EBRT) is the most common form used. Newer forms of radiation have been developed to more accurately target radiation to the tumor site.

  • Three-dimensional conformal radiation therapy (3D-CRT) uses precise mapping to shape and aim radiation beams at the tumor(s) from multiple directions, typically causing less damage to normal tissue.
  • Stereotactic body radiotherapy (SBRT) is a form of 3D-CRT offering precision delivery of high-dose radiation through beams aimed at the tumor from multiple directions. SBRT may be the primary treatment for small tumors or early-stage cancers when a person cannot undergo surgery or makes the decision not to have surgery.
  • Intensity-modulated radiation therapy (IMRT) is an advanced form of 3D-CRT that delivers radiation from a machine that moves around the person, aiming beams at varying strengths for increased precision. This technique may be used to treat tumors located near sensitive areas such as the spinal cord.
  • Proton beam therapy destroys cancer cells by using charged particles called protons. This treatment typically results in less damage to healthy tissue and fewer side effects than traditional radiation therapy.

Targeted Therapy

Targeted therapy is systemic therapy directed at proteins involved in making cancer cells grow but that do not have proven biomarkers. Monoclonal antibodies (mAbs) are laboratory-made anti-bodies that are designed to target specific tumor antigens. They can work in different ways, such as flagging targeted cancer cells for destruction, blocking growth signals and receptors and delivering other therapeutic agents directly to targeted cancer cells.

Monoclonal antibodies block the EGFR or vascular endothelial growth factor (VEGF) abnormality or its receptor; these are always given with chemotherapy.

Angiogenesis inhibitors shut down VEGF, a protein that is essential for creating blood vessels. With no vessels to supply blood, the tumor eventually “starves” and dies. Angiogenesis inhibitors are often given in combination with chemotherapy. Some of the treatments are antibodies that are given intravenously, and some are oral TKIs.

Radiofrequency Ablation

Radiofrequency ablation may be an option for small tumors when surgery is not advisable or if the person chooses not to have surgery. In this procedure, a needle placed directly into the tumor passes a high-frequency electrical current that destroys cancer cells with intense heat.

Cryosurgery

Cryosurgery, also called cryoablation and cryotherapy, kills cancer cells by freezing them with a probe or another instrument super-cooled with liquid nitrogen or similar substances. An endoscope, which is a thin tube-like instrument, is used for this procedure to treat tumors in the lungs’ airways.

Photodynamic Therapy

Photodynamic therapy is treatment with drugs that become active when exposed to light and kill cancer cells. A drug that is not active until it is exposed to light is injected into a vein. The drug collects more in cancer cells than in normal cells. Fiber optic tubes are then used to carry the laser light to the cancer cells, where the drug becomes active and kills the cells.

This treatment causes little damage to healthy tissue. It is used mainly to treat tumors on or just under the skin or in the lining of internal organs. When the tumor is in the airways, it is given directly to the tumor through an endoscope.

It is approved for relief of symptoms (such as breathing problems or bleeding) in NSCLC and can also treat small tumors.

Clinical Trials

Clinical trials are underway to find effective treatments for other abnormalities. Researchers are also looking for ways to improve existing treatments, such as surgery and radiation therapy, while reducing side effects.

Other areas of research include discovering new biomarkers that may be used to diagnose or treat lung cancer, finding improved methods to quit smoking, identifying better ways of reducing symptoms of cancer and its treatment, and improving a person’s quality of life.

 
Commonly Used Medications
Chemotherapy
carboplatin (Paraplatin)
cisplatin (Platinol)
docetaxel (Docefrez, Taxotere)
etoposide (Etopophos)
gemcitabine (Gemzar)
lurbinectedin (Zepzelca)
methotrexate (Trexall)
nab-paclitaxel (Abraxane)
paclitaxel (Taxol)
pemetrexed (Alimta)
topotecan (Hycamtin)
vinorelbine (Navelbine)
Immunotherapy
Checkpoint inhibitors
  • atezolizumab (Tecentriq)
  • durvalumab (Imfinzi)
  • nivolumab (Opdivo)
  • pembrolizumab (Keytruda)
Molecular therapy
Anaplastic lymphoma kinase (ALK) rearrangement
  • alectinib (Alecensa)
  • brigatinib (Alunbrig)
  • ceritinib (Zykadia)
  • crizotinib (Xalkori)
  • loratinib (Lorbrena)
BRAF mutation
  • dabrafenib (Tafinlar)/trametinb (Mekinist)
Epidermal growth factor receptor (EGFR) mutation
  • afatinib (Gilotrif)
  • dacomitinib (Vizimpro)
  • erlotinib (Tarceva)
  • gefitinib (Iressa)
  • osimertinib (Tagrisso)
MET exon 14 skipping mutation
  • capmatinib (Tabrecta)
Neurotrophic receptor tyrosine kinase (NTRK) gene fusion
  • larotrectinib (Vitrakvi)
RET fusion-positive alteration
  • selpercatinib (Retevmo)
ROS1 fusion
  • crizotinib (Xalkori)
  • entrectinib (Rozlytrek)
Targeted Therapy
Epidermal growth factor receptor (EGFR) inhibitor
  • necitumumab (Portrazza)
Vascular endothelial growth factor (VEGF) inhibitors (angiogenesis inhibitors)
  • bevacizumab (Avastin)
  • bevacizumab-awwb (Mvasi)
  • ramucirumab (Cyramza)
Some Possible Combinations
atezolizumab (Tecentriq) with bevacizumab (Avastin) with carboplatin (Paraplatin) and paclitaxel (Taxol)
atezolizumab (Tecentriq) with paclitaxel protein-bound (Abraxane) and carboplatin (Paraplatin)
bevacizumab (Avastin) with carboplatin (Paraplatin) and paclitaxel (Taxol)
bevacizumab-awwb (Mvasi) with carboplatin (Paraplatin) and paclitaxel (Taxol)
bevacizumab-bvzr (Zirabev) with carboplatin (Paraplatin) and paclitaxel (Taxol)
docetaxel (Taxotere) with cisplatin (Platinol)
docetaxel injection with cisplatin (Platinol)
durvalumab (Imfinzi) with etoposide (Etopophos) and either carboplatin (Paraplatin) or cisplatin (Platinol)
etoposide (Etopophos) with cisplatin (Platinol)
gemcitabine (Gemzar) and cisplatin (Platinol)
ipilimumab (Yervoy) with nivolumab (Opdivo)
necitumumab (Portrazza) with gemcitabine (Gemzar) and cisplatin (Platinol)
nivolumab (Opdivo) with ipilimumab (Yervoy) and platinum-doublet chemotherapy
paclitaxel protein-bound (Abraxane) with carboplatin (Paraplatin)
paclitaxel (Taxol) with cisplatin (Platinol)
pembrolizumab (Keytruda) with carboplatin (Paraplatin) and either paclitaxel (Taxol) or paclitaxel protein-bound (Abraxane)
pembrolizumab (Keytruda) with pemetrexed (Alimta) and platinum chemotherapy
pemetrexed (Alimta) with pembrolizumab (Keytruda) and platinum chemotherapy
pemetrexed (Alimta) with cisplatin (Platinol)
ramucirumab (Cyramza) with docetaxel (Taxotere)
ramucirumab (Cyramza) with erlotinib (Tarceva)
vinorelbine (Navelbine) with cisplatin (Platinol)
       As of 6/1/20

Palliative Care Services Provide Comfort For People With Metastatic Disease

As advances in lung cancer treatment continue to be developed, many people with metastatic disease may live longer. As a result, survivors are challenged with managing the long-term realities of advanced lung cancer and its accompanying treatments while trying to maintain the quality of life they desire.

Palliative care is a medical specialty designed to help people living with serious or life-threatening illnesses and their families meet physical, emotional, social and spiritual needs. This type of supportive care focuses on addressing disease symptoms, minimizing treatment side effects and managing pain.

For example, individuals with metastatic lung cancer often experience shortness of breath, which may be caused by fluid buildup in the area surrounding the lungs, tumor growth that restricts an airway or other factors. Some people with advanced lung disease may have decreased heart function if tumors spread to that area, causing fluid buildup. Your palliative care specialist can recommend the best procedure to resolve the problem and make you more comfortable.

Although palliative care is beneficial at any stage of cancer, it’s especially encouraged for people with metastatic disease. Over time, continual treatment can take a heavy toll physically and emotionally on patients as well as their loved ones. Your palliative care specialist/team is there to provide strategies, resources and ideas to help you cope. Ask your nurse navigator how to take advantage of these services.

Medication Adherence is Crucial to Effective Treatment

Today, an increasing number of cancer treatments are oral therapies (pills). People undergoing cancer treatment may prefer the at-home option of oral therapy instead of IV therapy. Oral therapy is just as potent as IV therapy, and to be fully effective, every dose must be taken with the same kind of accuracy, precise timing and safety precautions.

Taking the right drug in the right dose at the right time – every time – for as long as prescribed is referred to as medication adherence (or treatment adherence). Most cancer therapies are designed to maintain a specific level of drugs in your system for a certain time based on your cancer type and stage, your overall health, previous therapies and other factors. Even small changes to your oral therapy regimen can disrupt your treatment and affect its outcome.

Getting off schedule, missing doses, taking an incorrect dosage or not following the treatment instructions can lead to increased side effects, treatment delays or hospitalization. The most serious consequence is a poor outcome, including cancer progression or recurrence.

Taking your cancer treatment correctly may sound simple, but it takes serious effort and coordination to make it happen, particularly if you take numerous daily medications. Explore the many tools available to help you stay on track. Set alarms or phone reminders, make a daily medication schedule, ask loved ones to remind you, track medications on a calendar, check out medication trackers online or use smartphone apps.

Quit Smoking to Increase Treatment Effectiveness

Many tobacco users who have been diagnosed with lung cancer believe there is no longer any reason to quit. This isn’t true. There are many benefits of quitting, and the most important is that your treatments will be more effective when you no longer use tobacco.

Other benefits of quitting include the following:

  • Reduces lung inflammation that can lead to increased cancer growth
  • May decrease the severity of side effects, making treatment easier
  • Lessens the risk of infection and may speed healing after surgery
  • Improves immune system health, which is important in disease control
  • Lowers blood pressure and decreases heart rate
  • Decreases the risk of secondary cancers and other conditions linked to tobacco use
  • May improve your senses of smell and taste

You may feel overwhelmed by the idea of quitting. You may also experience “disease stigma,” which happens when others cast blame because they may make assumptions about your lifestyle choices.

Ask your health care team about the options your treatment facility and community may offer to help people quit using tobacco. Many resources are available, such as smoking cessation programs, local support groups, call lines, text-based help and online assistance. The following resources may also help:

  • American Cancer Society: www.cancer.org, 800-227-2345
  • BecomeAnEx: www.becomeanex.org
  • Freedom from Smoking: www.lung.org/stop-smoking/join-freedom-from-smoking
  • National Cancer Institute Smoking Quitline: 877-44U-QUIT (877-448-7848)
  • North American Quitline Consortium: naquitline.org
  • Quitter’s Circle: www.quitterscircle.com
  • Smokefree.gov: smokefree.gov, 800-784-8669
  • SmokefreeTXT: smokefree.gov/tools-tips/text-programs
  • Tobacco Quitline: 1-800-QUIT-NOW (800-784-8669)
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