Treatments for recurrent non–small cell lung cancer

Recurrent non−small cell lung cancer means that the cancer has come back after it has been treated. The following are treatment options for recurrent non−small cell lung cancer. Your healthcare team will suggest treatments based on your needs and work with you to develop a treatment plan.

Treatment decisions are based on:

• where the cancer has come back

• what treatments have already been given

• any side effects that you have from treatment you've already been given

• if the cancer has certain gene changes

• your overall health

Chemotherapy may be used to treat recurrent non–small cell lung cancer if you are well enough to have it. It is the treatment offered if there are no genetic changes (mutations) that can be identified in the lung cancer tumours. (If there are, you will be offered targeted therapy that is based on those mutations.) If chemotherapy was not previously used as a treatment for non–small cell lung cancer, combination chemotherapy may be used.

The most common chemotherapy drug combination used to treat recurrent 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 adenocarcinoma 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 if you are in poor health. A single chemotherapy drug may also be offered if cisplatin can't be used anymore because of side effects. The drugs that may be used include:

• gemcitabine

• paclitaxel

• docetaxel

Targeted therapy is usually offered for non–small cell lung cancer that has come back after treatment. The type of targeted therapy given will depend on the type of genetic change found during diagnosis using cell and tissue studies.

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+).

Erlotinib (Tarceva) may be used to treat non−small cell lung cancer that has come back after 2 or 3 different types of chemotherapy. This drug is offered for recurrent non−small cell lung cancer whether the cancer is EGFR+ or not. Erlotinib may also be offered as maintenance therapy for EGFR+ tumours after chemotherapy has finished.

Gefitinib (Iressa) or afatinib (Giotrif) may be used to treat recurrent EGFR+ non–small cell lung cancer if targeted therapy has not been used before. Afatinib may also be given to people with squamous cell non-small cell lung cancer if the cancer has stopped responding to chemotherapy.

Osimertinib (Tagrisso) may be offered for recurrent EGFR+ non-small cell lung cancer that has developed a mutation to the T790M gene. You would only be offered this drug after being treated with other drugs that target EGFR+ tumours.

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 recurrent 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. Cancer cells that have the ALK mutation are called ALK positive (ALK+). A very small number of non–small cell lung cancers are ALK+.

If targeted therapy drugs have not yet been used, the drugs that may be offered for ALK+ recurrent non–small cell lung cancer are:

• crizotinib (Xalkori)

• ceritinib (Zykadia)

If recurrent ALK+ non–small cell lung cancer has stopped responding to other targeted therapy, the following drugs may be offered:

• alectinib (Alecensaro)

• brigatinib (Alunbrig)

• lorlatinib (Lorbrena)

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+ recurrent non–small cell lung cancer may be treated with crizotinib if you haven't had it before.

Entrectinib (Rozlytrek) may be offered for ROS1+ recurrent 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 recurrent 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, 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+).

Recurrent 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.

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

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 recurrent non−small cell lung cancer.

Immunotherapy drugs may be used to treat non–small cell lung cancer after it has stopped responding to chemotherapy or targeted therapy.

The most common type of immunotherapy drug used to treat recurrent non−small cell lung cancer are PD-1 or PD-L1 checkpoint inhibitors.

The following PD-1 or PD-L1 checkpoint inhibitor drugs are used to treat recurrent non−small cell lung cancer. You will only be offered one type because research suggests that if a cancer stops responding to a specific checkpoint inhibitor, it will not respond to a different drug.

Nivolumab (Opdivo) may be used to treat non–small cell lung cancer that has stopped responding to chemotherapy with cisplatin or carboplatin or has come back after chemotherapy. It may also be given for EGFR+ and ALK+ recurrent non–small cell lung cancer that has stopped responding to targeted therapy.

Pembrolizumab (Keytruda) may be used for recurrent non–small cell lung cancer that is PD-L1 positive and has stopped responding to chemotherapy with cisplatin or carboplatin. It may also be given for EGRF+ and ALK+ recurrent non–small cell lung cancer that has stopped responding to targeted therapy.

Atezolizumab (Tecentriq, Tecentriq SQ) may be used by itself as the first treatment for recurrent non–small cell lung cancer that does not have EGFR or ALK gene mutations. It is also used to treat recurrent non−small cell lung cancer that has stopped responding to chemotherapy or has come back after chemotherapy. Atezolizumab may also be used to treat recurrent EGFR+ or ALK+ non–small cell lung cancer that has stopped responding to a targeted therapy drug used to treat these genetic changes.

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.

Endobronchial therapies remove a blockage caused by the cancer inside the lung. They are used to treat and prevent symptoms caused by recurrent 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. You may be offered:

• bronchial debridement

• stent placement

• brachytherapy

• laser surgery

• cryotherapy

• electrocautery

• photodynamic therapy (PDT)

External radiation therapy may be used for recurrent non–small cell lung cancer if it hasn't been used as a treatment before. It may be offered to people who are not able to have chemotherapy to treat a recurrence in the lymph nodes in the chest or the lung and to relieve symptoms caused by the cancer (palliative radiation therapy).

Radiation therapy may also be used to treat recurrent non–small cell lung cancer that has spread to the bones or the brain. If you cannot have external radiation therapy because your lungs are not working well, you may be offered brachytherapy (internal radiation therapy).

Brachytherapy may also be used as an endobronchial therapy to treat a non–small cell lung cancer tumour by removing the blockage caused by the cancer inside the lung. This can also be called endobronchial radiation therapy or endobronchial brachytherapy.

Surgery may be used to treat recurrent 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.

Surgery to remove a local recurrence in the lung may be offered if you are 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.