Putting the immune system to work: immunotherapy in non-small cell lung cancer

This review examines the use of immunotherapy in the treatment of non-small cell lung cancer.

Non-small cell lung cancer is often diagnosed at more advanced stages, as it does not present with many symptoms. The first-line treatment for most patients is platinum-based chemotherapy (for example carboplatin [Paraplatin]), while patients who have certain genetic factors, such as mutations to the epidermal growth factor receptor, may also receive treatments targeted to those mutations. Bevacizumab (Avastin), which inhibits the formation of blood vessels a tumor needs for growth, is often used in conjunction with chemotherapy in some patients.

Despite these treatment options, survival rates for non-small cell lung cancer remain low, particularly for patients with metastatic disease, which has spread to other areas of the body. Immunotherapies are treatments that stimulate the immune system to fight tumor cells the way it fights a bacteria or virus. Immunotherapies have been shown to be effective against other forms of cancer, such as melanoma, and are now being developed as a new form of therapy for non-small cell lung cancer.

Current clinical trials are exploring multiple immunotherapies for use in non-small cell lung cancer. Many tumor cells have ways of “shutting down” the immune response, therefore, a main function of immunotherapies is to allow T-cells (white blood cells that travel through the body, looking for abnormal cells or infections) to act against tumor cells.

Mucinous glycoprotein-1 is an antigen (a molecule that produces an immune response) that is often expressed on some non-small cell lung cancer cells. L-BLP25 (Tecemotide) and TG4010 are two vaccines that work with mucinous glycoprotein-1. Trials have shown increased survival times with both vaccines either following or in conjunction with chemotherapy. Trials are ongoing to determine their effectiveness as first-line treatments.

Belagenpumatucel-L (Lucanix) decreases the growth of tumor cells and was shown to increase survival times when given at high doses (581 days) compared to lower doses (252 days).

Two types of immunotherapies that prevent cancer cells from blocking an immune response are ipilimumab (Yervoy) and nivolumab. Ipilimumab has been shown to improve survival rates in melanoma patients. Trials have shown that a phased dose with chemotherapy, for example chemotherapy followed by ipilimumab, improved the response to chemotherapy and overall survival time (12.2 months) in patients with squamous non-small cell lung cancer, in comparison to patients who received chemotherapy and ipilimumab at the same time (9.7 months).

Nivolumab doses of 3 mg/kg have been found to lead to overall survival rates of 18.2 months for non-squamous non-small cell lung cancer, compared to 9.5 months for squamous non-small cell lung cancer. Further trials are ongoing to evaluate the safety and effectiveness of this second-line treatment.

Other possible second-line treatments under evaluation include MK-3475, which has been shown to be effective against melanoma, and is currently being studied in combination with the chemotherapy agent docetaxel (Taxotere); and combinations of immunotherapies, such as ipilimumab and nivolumab. These studies are still in the early stages.

The most common adverse side effects noted with immunotherapies have been gastrointestinal problems (nausea, diarrhea) in 9%–32% of patients and dermatological problems (skin problems such as rashes) in 12%–44%.

This review concluded that immunotherapies have the potential to be beneficial non-small cell lung cancer therapies. Studies are ongoing to determine appropriate doses, safety, and effectiveness.