New treatment avenues for non-small cell lung cancer

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

Despite improvements in treatment options, including therapies that target common mutations (abnormal genes) such as those in the epidermal growth factor receptor (EGFR) gene, survival rates in non-small cell lung cancer are still low. Therefore, new treatments are being investigated for these patients, including immunotherapies.

Immunotherapies target the immune system, the body’s defense against invading organisms. These therapies increase the likelihood that the immune system will attack cancer cells as it would a virus or bacteria, and hopefully slow the cancer growth. While immunotherapies have been used successfully for many types of cancer, including prostate cancer and melanoma (skin cancer), many of the immunotherapy agents have not been effective for lung cancer.

Recent evidence has shown that many tumor cells have proteins which allow them to hide from the immune system. Targeting these proteins may be a more effective form of treatment for certain cancers, including non-small cell lung cancer.

This article examined recent research involving the use of immunotherapies in non-small cell lung cancer. The authors discuss different methods of making tumor cells visible to the immune system, and present current research into therapies exploiting these methods.

The protein CTLA-4 is expressed (present) in 51%–87% of non-small cell lung cancer tumors, and can block the activation of T cells (a type of white blood cell involved in immunity). Inhibiting CTLA-4, with a treatment such as ipilimumab (Yervoy), can increase the immune response to cancer cells. Ipilimumab has been found to be effective in melanoma. Current trials examining its use in non-small cell lung cancer have shown that it is effective when used in combination with chemotherapy. It significantly increased progression-free survival (5.7 months from treatment until disease progression) compared to patients receiving placebo (a substance that has no therapeutic effect; 4.6 months) when it was delivered early in the treatment cycles. A 3.9 month improvement was also seen in overall survival (time from treatment until death from any cause) compared to placebo, but this was not statistically significant. Further trials are underway to determine the effectiveness of ipilimumab in non-small cell lung cancer.

Another protein, the receptor PD-L1, is present in 27%–57.5% of non-small cell lung cancer tumors, and also works to hide tumor cells from T cells. Multiple possible PD-L1 inhibitors are currently being researched. Early results from one such treatment, MPDL3280A, has led to an overall response rate (such as tumor shrinkage) of 24% and a 24-week progression-free survival rate of 46%. The overall response rate was slightly higher in patients who were current/former smokers (25%) compared to those who had never smoked (16%).

Ongoing trials are examining inhibiting multiple other proteins, including PD-1, KIR, and OX-40. Combination therapy is also being investigated, it involves combining immunotherapies with other known non-small cell lung cancer treatments, in hopes of increasing response rates. Known treatments include chemotherapies and treatments that target specific mutations such as EGFR. 

This study suggested that the discovery that tumors have ways of hiding from the immune system opened the door to new treatment possibilities. However, future research is needed to determine the appropriate method and timing of such treatments.