Treatment Update: Non-Small Cell 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 often used, either alone or in combination with chemotherapy. 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 stereotactic body radiation therapy (SBRT), also called stereotactic ablative body radiation (SABR), is frequently 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. Multiple studies have shown that SBRT is an excellent alternative for patients who are not able or do not want to undergo 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.

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). 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, 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.

Targeted Therapy

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 August 2022, the FDA approved trastuzumab deruxtecan (Enhertu) for the treatment of unresectable or metastatic NSCLC with HER2 (ERBB2) mutations which has been treated by a prior systemic therapy.

• 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.

• Durvalumab (Imfinzi). In 2018, the FDA approved durvalumab for the treatment of locally advanced NSCLC after treatment with chemotherapy and radiation.

• 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.

Clinical trials are the standard by which we measure the worth of new treatments and the quality of life of patients as they receive those treatments. For this reason, doctors and researchers urge people with cancer to take part in clinical trials.

Your doctor can guide you in making a decision about whether a clinical trial is right for you. Here are a few things that you should know:

• Often, people who take part in clinical trials gain access to and benefit from new treatments.
• Before you participate in a clinical trial, you will be fully informed as to the risks and benefits of the trial, including any possible side effects.
• Most clinical trials are designed to test a new treatment against a standard treatment to find out whether the new treatment has any added benefit.
• You can stop taking part in a clinical trial at any time for any reason.