Treatment Update: Lung Cancer

After your diagnosis, you and your health care team will discuss the best way to proceed with your treatment. Factors that influence the choice of treatment include the type of lung cancer, its stage and whether it has a genetic mutation.

Surgery

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. When additional precision is needed, robotic surgery is sometimes an option for the removal of tumors in the lung.

Radiation Therapy

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, called a linear accelerator, that directs multiple beams of radiation to the tumor. The use of CT (computerized tomography) 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 destroys more cancer cells and minimizes the impact on healthy tissue. Research is ongoing to determine those people with early-stage lung cancer who 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 with minimal doses delivered to nearby areas of the body. This type of radiation is especially useful for people whose tumor is close to a critical structure, such as the spinal cord, or who have previously received radiation.

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.

Prophylactic cranial irradiation helps lower the risk of SCLC spreading to the brain. It is mostly used in the treatment of limited stage SCLC, but it may also help some people with extensive stage SCLC.

Chemotherapy

Chemotherapy, the use of drugs to destroy cancer cells by stopping the ability of the cells to grow and divide, has long been a mainstay of lung cancer treatment. Chemotherapy is extremely effective in treating SCLC, and is also used to treat many cases of NSCLC. Chemotherapy can also be helpful for people whose tumors have (or will be) removed by surgery, and in combination with radiation (chemoradiation) for locally advanced cancer. It is also an important part of treatment for many 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). Most chemotherapy treatment approaches include either cisplatin or carboplatin in combination with another chemotherapy drug, often etoposide.

• 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, and for 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) and docetaxel (Taxotere). These drugs 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.

• Etoposide (Etopophos, Vepesid). Etoposide is used in combination with other cancer medications, including chemotherapy, for the treatment of SCLC.

• Lurbinectedin (Zepzelca) and Topotecan (Hycamtin). These chemotherapies are for the treatment of metastatic SCLC that has progressed after platinum-based chemotherapy.

Targeted Therapy

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 NSCLC 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, six medications are approved treatment options in the United States for lung cancer that has this gene mutation:

• Erlotinib (Tarceva). 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). In 2018, the FDA approved dacomitinib as an initial treatment for NSCLC with certain EGFR gene mutations as detected by an FDA-approved test.

• Amivantamab-vmjw (Rybrevant). In May 2021, the FDA approved amivantamab-vmjw for the treatment of NSCLC with EGFR exon 20 insertion mutations.

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 NSCLC 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 NSCLC 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 (Alecensa). Alectinib was approved in 2015 for people with ALK-positive NSCLC who were previously 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 NSCLC that was previously treated with crizotinib.

• Lorlatinib (Lorbrena). In 2018, lorlatinib was approved for the treatment of ALK-positive metastatic NSCLC that progressed while being treated with crizotinib or another ALK inhibitor. In March 2021, the approval was extended to the first-line treatment of NSCLC that has the ALK mutation.

There are other targeted therapies for the treatment of NSCLC that has other specific gene mutations:

• In 2017, the FDA approved dabrafenib and trametinib, administered in combination, for people whose NSCLC has a mutation of the BRAF V600E gene.

• In September 2020, the FDA granted approval to pralsetinib (Gavreto) for the treatment of metastatic RET fusion-positive NSCLC.

• In March 2021, the FDA approved tepotinib (Tepmetko) for the treatment of metastatic NSCLC that has the MET exon 14 skipping alteration.

• In June 2021, the FDA approved sotorasib (Lumakras) as a first-line treatment for NSCLC that has the KRAS G12C genetic mutation and that has been treated with at least one prior therapy.

• In September 2021, the FDA approved mobocertinib (Exkivity) for the treatment of locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations and which has progressed on or after platinum-based chemotherapy.

• In December 2022, the FDA granted accelerated approval to adagrasib (Krazati) for the treatment of KRAS G12C-mutated locally advanced or metastatic NSCLC.

Immunotherapy

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. In 2020, the FDA approved nivolumab in combination with ipilimumab (Yervoy) as first-line treatment for people with metastatic NSCLC whose tumors have the PD-L1 characteristic.

• 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. It was subsequently 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. In January 2023, the approval was expanded to include treatment, following surgery and platinum-based chemotherapy, of stage IB, II, or IIIA NSCLC.

• 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 2018, the FDA approved durvalumab for the treatment of locally advanced NSCLC after treatment with chemotherapy and radiation. In March 2020, the approval was extended to the first-line treatment of extensive stage SCLC, in combination with etoposide and either carboplatin or cisplatin.

• Cemiplimab-rwlc (Libtayo). In February 2021, the FDA approved cemiplimab-rwlc for the first-line treatment of NSCLC that has high PD-L1 expression and cannot be treated with surgery or chemoradiation.

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 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) 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) 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.

All cancer treatments can cause side effects. It’s important that you report any side effects that you experience to your health care team so they can help you manage them. Report them right away—don’t wait for your next appointment. Doing so will improve your quality of life and allow you to stick with your treatment plan. It’s important to remember that not all people experience all side effects, and people may experience side effects not listed here.

Side Effects of Radiation Therapy

Fatigue is the most common side effect of radiation. Additionally, changes to the skin can frequently occur. The changes can include dryness, swelling, peeling, redness and (rarely) blistering. If a reaction occurs, contact your health care team so the appropriate treatment can be prescribed. It’s especially important to contact your health care team if there is any open skin or painful area, as this could indicate an infection. Infections can be treated with an oral antibiotic or topical antibiotic cream.

Side Effects of Chemotherapy

The side effects of chemotherapy depend on the type and dose of drugs given and the length of time they are used, and can include:

• Hair loss
• Increased risk of infection (from having too few white blood cells)
• Easy bruising or bleeding
• Changes in memory or thinking
• Peripheral neuropathy (numbness or tingling in hands and feet)

Side Effects of Targeted Therapy

Targeted therapy doesn’t have the same effect on the body as do chemotherapy drugs, but it can still cause side effects. Side effects of targeted therapies can include diarrhea, liver problems (such as hepatitis and elevated liver enzymes), nerve damage, high blood pressure and problems with blood clotting and wound healing.

Side Effects of Immunotherapy

Immunotherapy travels through the bloodstream, helping to prompt an immune response. Because it can trigger an attack on healthy cells as well as cancer cells, certain side effects may be experienced, including fatigue, decreased appetite and digestive tract symptoms.

Some side effects may occur across treatment approaches. This section provides tips and guidance on how to manage these side effects should they occur.

Managing Digestive Tract Symptoms

Nausea and vomiting

• Avoid food with strong odors, as well as overly sweet, greasy, fried or highly seasoned food.

• Eat meals that are chilled, which often makes food more easily tolerated.

• Nibble on dry crackers or toast. These bland foods are easy on the stomach.

• Having something in your stomach when you take medication may help ease nausea.

Diarrhea

• Drink plenty of water. Ask your doctor about using drinks such as Gatorade which provide electrolytes. Electrolytes are body salts that must stay in balance for cells to work properly.

• Over-the-counter medicines such as loperamide (Imodium A-D and others) and prescription drugs are available for diarrhea but should be used only if necessary. If the diarrhea is bad enough that you need medicine, discuss it with your doctor or nurse.

• Choose fiber-dense foods such as whole grains, fruits and vegetables, all of which help form stools.

• Avoid food high in refined sugar and those sweetened with sugar alcohols such as sorbitol and mannitol.

Managing loss of appetite

• Eating small meals throughout the day is an easy way to take in more protein and calories, which will help maintain your weight. Try to include protein in every meal.

• To keep from feeling full early, avoid liquids with meals or take only small sips (unless you need liquids to help swallow). Drink most of your liquids between meals.

• Keep high-calorie, high-protein snacks on hand such as hard-boiled eggs, peanut butter, cheese, ice cream, granola bars, liquid nutritional supplements, puddings, nuts, canned tuna or trail mix.

• If you are struggling to maintain your appetite, talk to your health care team about whether appetite-building medication could be right for you.

Managing Fatigue

Fatigue (extreme tiredness not helped by sleep) is one of the most common side effects of many cancer treatments. If you are taking a medication, your doctor may lower the dose of the drug, as long as it does not make the treatment less effective. If you are experiencing fatigue, talk to your doctor about whether taking a smaller dose is right for you.

There are a number of other tips for reducing fatigue:

• Take several short naps or breaks during the day.
• Take short walks or do some light exercise, if possible.
• Try easier or shorter versions of the activities you enjoy.
• Ask your family or friends to help you with tasks you find difficult or tiring.
• Save your energy for things you find most important.

Fatigue can be a symptom of other illnesses, such as anemia, diabetes, thyroid problems, heart disease, rheumatoid arthritis and depression. So be sure to ask your doctor if they think any of these conditions may be contributing to your fatigue.

Managing Pain

To help your doctor prescribe the best medication, it’s useful to give an accurate report of your pain. Keep a journal that includes information on:

• Where the pain occurs
• When the pain occurs
• How long it lasts
• How strong it is on a scale of 1 to 10, with 1 being the least amount of pain and 10 the most intense
• What makes the pain feel better and what makes it feel more intense

There are a number of options for pain relief, including prescription and over-the-counter medications. It’s important to talk to a member of your health care team before taking any over-the-counter medication to determine if they are safe and will not interfere with your treatments.

Physical therapy, acupuncture and massage may also be of help in managing your pain. Consult with a member of your health care team before beginning any of these activities.

Frequently Asked Questions

Q: My breathing has been affected by surgery and chemotherapy. What can I do about this?

A: When surgery reduces the size of the lungs, you cannot take in as much air. Some medications also change lung function and lead to shortness of breath. Any time you have difficulty breathing, you should report it to your doctor, as there is pulmonary (lung) rehabilitation therapy that may be available to you. To improve lung function, this therapy may include exercise training, energy-conserving techniques, breathing strategies and nutritional counseling.

Q: I had Stage 1A NSCLC surgically removed. My doctor says I don’t need chemotherapy or any other type of treatment. Should I get a second opinion?

A: If your cancer was truly Stage 1A (tumor of 3 centimeters or smaller that had not spread beyond the lung), treatment after successful surgery is generally not recommended. However, it’s important to get a computerized tomography (CT) scan every six months for the first two years after surgery, to check for recurrence and any new cancer. After the first two years, your doctor will recommend how frequently you should get a CT scan.

Q: I have SCLC and recently read about trilaciclib and its impact on bone marrow. What is it?

A: Bone marrow is the spongy tissue inside bones where blood cells are made. Trilaciclib (Cosela) is designed to help protect bone marrow cells from damage caused by certain types of chemotherapy. Protecting bone marrow function may help make chemotherapy safer and allow people to complete their course of treatment as prescribed.