Treatments for stage 4 non–small cell lung cancer

The following are treatment options for stage 4 non−small cell lung cancer. Your healthcare team will suggest treatments based on your needs and work with you to develop a treatment plan.

Chemotherapy may be offered for stage 4 non–small cell lung cancer if there are no genetic changes (mutations) that can be identified in the lung cancer tumours using cell and tissue studies. You need to be well enough to have chemotherapy.

The most common chemotherapy drug combination used to treat stage 4 non−small cell lung cancer is cisplatin or carboplatin with gemcitabine. Other chemotherapy combinations that may be used include:

• cisplatin or carboplatin and docetaxel (Taxotere)

• carboplatin and paclitaxel

• gemcitabine and docetaxel

• gemcitabine and vinorelbine

• cisplatin and pemetrexed (Alimta) – only used for non-squamous types of non–small cell lung cancer

Pemetrexed may also be offered by itself as maintenance therapy to slow the return of lung cancer if the cancer has responded to chemotherapy. You will not be offered pemetrexed if you have already had it as part of your chemotherapy treatment.

Single drugs may be offered to treat stage 4 non–small cell lung cancer if you are in poor health. The drugs used include:

• gemcitabine

• paclitaxel

• docetaxel

Targeted therapy may be offered instead of chemotherapy for stage 4 non–small cell lung cancer if there are genetic changes to the lung cancer cells. The type of targeted therapy given will depend on the type of genetic mutation that was identified using cell and tissue studies.

If testing does not show genetic mutations that can be treated with targeted therapy, you will not be offered it as treatment for stage 4 non−small cell lung cancer tumours.

Sometimes genetic changes are found in the cells during chemotherapy. If so, you may have targeted therapy when chemotherapy is finished, or your healthcare team may switch you to the targeted therapy drug alone.

Epidermal growth factor receptor (EGFR) is a receptor on the surface of cells that sends signals to cells that allow them to grow and divide. A mutation in the EGFR gene can cause cancer cells to grow and divide more than normal. Cancer cells that have the EGFR mutation are called EGFR positive (EGFR+).

EGFR-positive stage 4 non−small cell lung cancer may be treated with erlotinib (Tarceva), gefitinib (Iressa) or osimertinib (Tagrisso) instead of chemotherapy.

Erlotinib may also be given as maintenance therapy for stage 4 non−small cell lung cancer after 4 cycles of chemotherapy with cisplatin or carboplatin.

The EGFR exon 20 insertion mutation happens when a small piece of genetic material gets added (inserted) into the area of the EGFR gene called the exon 20.

Targeted therapy drugs used for other EGFR mutations don't work for the exon 20 insertion mutation.

Amivantamab (Rybrevant) may be offered for stage 4 non–small cell lung cancer with the EGFR exon 20 insertion mutation if it doesn't respond to, or stops responding to, chemotherapy with cisplatin or carboplatin.

Anaplastic lymphoma kinase (ALK) is a protein that helps with cell growth and division. It is controlled by the ALK gene. A very small number of non–small cell lung cancers have a mutation in the ALK gene. Cancer cells that have the ALK rearrangement are called ALK positive (ALK+).

ALK-positive stage 4 non−small cell lung cancer may be treated with crizotinib (Xalkori). If you can't take crizotinib, other drugs that may be given are ceritinib (Zykadia), alectinib (Alecensaro) or brigatinib (Alunbrig).

The ROS1 gene makes a protein that is responsible for signals in cells and helps with cell growth. A mutation in the ROS1 gene can cause cancer cells to grow and divide more than normal. Cancer cells that have the ROS1 mutation are called ROS1 positive (ROS1+).

ROS1-positive stage 4 non−small cell lung cancer may be treated with crizotinib.

Entrectinib (Rozlytrek) may be offered for ROS1-positive stage 4 non–small cell lung cancer, if you have not been given crizotinib as a treatment.

KRAS G12C is a common genetic mutation found in people with non–small cell lung cancer. A tumour that has the KRAS G12C mutation is called KRAS G12C-positive.

Sotorasib (Lumakras) is a targeted therapy drug that can be used to treat people with stage 4 KRAS G12C-positive non–small cell lung cancer that have received at least one other systemic treatment.

BRAF is a protein that sends signals in cells and helps with cell growth. Changes in the BRAF gene, which is called BRAF V600E, can be found in higher amounts in some types of lung cancer. Cancer cells that have changes to this gene are called BRAF V600E positive (BRAF V600E+).

Stage 4 non–small cell lung cancer that is BRAF V600E positive may be treated with a combination of dabrafenib (Tafinlar) and trametinib (Mekinist).

Mutations in the NTRK gene can cause too much cell growth and lead to abnormal cells and cancer. Sometimes this mutation is found in non–small lung cancer. Cancer cells that have changes to this gene are called TRK fusion positive.

Stage 4 non−small cell lung cancer that is TRK fusion positive may be treated with larotrectinib (Vitrakvi).

MET exon 14 skipping mutations (METex 14) is a mutation that has been found in a small number of non–small cell lung cancer tumours.

Tepotinib (Tepmetko) or capmatinib (Tabrecta) may be used in people who have stage 4 non–small cell lung cancer that has METex 14 mutations.

The RET gene makes a protein that is responsible for signals in cells and in cell growth. A very small number of non–small cell lung cancers have a change in the RET gene. Cancer cells that have changes in the RET gene are called RET fusion–positive (RET+).

Stage 4 RET+ non–small cell lung cancer may be treated with Gavreto (pralsetinib) or Retevmo (selpercatinib) instead of chemotherapy.

Bevacizumab (Avastin, MVASI, Zirabev) is a type of targeted therapy called an angiogenesis inhibitor. It targets a protein called vascular endothelial growth factor (VEGF), which helps new blood vessels grow.

Bevacizumab is combined with the chemotherapy drugs carboplatin and paclitaxel. This combination may be offered for stage 4 non−small cell lung cancer.

Immunotherapy may be offered for stage 4 non−small cell lung cancer.

Pembrolizumab (Keytruda) may be used to treat non–small cell lung cancer that make too much PD-1.

Atezolizumab (Tecentriq) may be used alone or in combination with bevacizumab (Avastin) or biosimilar drugs, paclitaxel and carboplatin as the first treatment for non–small cell lung cancer that does not have EGFR or ALK gene mutations. It blocks the PD-L1 protein on cells that are making too much of this protein.

Nivolumab (Opdivo) combined with ipilimumab (Yervoy) may be used as the first treatment for metastatic non–small cell lung cancer that does not have EGFR or ALK gene mutations and has very little PD-L1 in the cancer cells. Nivolumab and ipilimumab may also be used in combination with cisplatin or carboplatin plus another chemotherapy drug.

Cemiplimab (Libtayo) is a PD-L1 checkpoint inhibitor. It may be offered for non−small cell lung cancer that makes a lot of PD-L1, but doesn't have changes to other genes such as EGFR, ALK or ROS-1.

Endobronchial therapies remove a blockage caused by the cancer inside the lung. They are used to treat and prevent symptoms caused by stage 4 non–small cell lung cancer, such as coughing, problems breathing, bleeding and pain.

The type of endobronchial therapy used will depend on how quickly the symptoms must be treated.

External beam radiation therapy may be used for stage 4 non–small cell lung cancer if you can't have chemotherapy. It is also used to relieve symptoms caused by the cancer (palliative radiation therapy). Radiation therapy may also be used to treat non–small cell lung cancer that has spread to the bones or the brain.

Find out more about bone metastases and brain metastases.

Surgery may be used to treat stage 4 non–small cell lung cancer that has spread to the adrenal gland, brain or liver. For brain metastases, it is used when there is only one area of cancer found in the brain. For liver metastases, it may be offered if there is one area of cancer or a few areas of cancer found close together.

Some people with stage 4 non–small cell lung cancer are not well enough to have surgery.

You may want to consider a type of care to make you feel better without treating the cancer itself. This may be because the cancer treatments don't work anymore, they're not likely to improve your condition or they may cause side effects that are hard to cope with. There may also be other reasons why you can't have or don't want cancer treatment.

Talk to your healthcare team. They can help you choose care and treatment for advanced cancer.

Talk to your doctor about clinical trials open to people with non−small cell lung cancer in Canada. Clinical trials look at new ways to prevent, find and treat cancer. Find out more about clinical trials.