Immunologic Therapy or Immuno-oncology

Immunotherapy treatment of NSCLC has also progressed considerably over the past few decades and has now become a standard treatment. The immune system is a network of cells, tissues, and biologic substances that defend the body against viruses, bacteria, and cancer. Doctors have been trying for years to find ways to harness an individual’s immune system to fight cancer.

The immune system recognizes cancer cells as foreign and can eliminate them or keep them in check—up to a point. Cancer cells are very good at finding ways to avoid immune destruction however, so the goal of immunotherapy is to help the immune system eliminate cancer cells by either activating the immune system directly or inhibiting the mechanisms of suppression of the immune system.

Recent promising clinical results have generated an explosion of interest and research in the field of immuno-oncology. Researchers are mainly focused on two promising types of immunotherapy. One type creates a new, individualized treatment for each patient by removing some of the person’s immune cells, altering them genetically to kill cancer, and then infusing them back into the bloodstream. This procedure has been pioneered mainly in the treatment of leukemia or lymphoma.

The second type of immunotherapy is a group of drugs that do not have to be tailored to each patient; these are called checkpoint inhibitors. These drugs block a mechanism, called a checkpoint, that cancer uses to shut down the immune system.1,2 These drugs have been approved by the US Food and Drug Administration (FDA) to treat several types of cancer, including NSCLC.

Checkpoint inhibitors work on killer T-cells—the white blood cells that are often described as the soldiers of the immune system. T-cells have built-in brakes, or checkpoints, to turn them off and keep them from attacking normal tissue, which could result in autoimmune diseases. One checkpoint stops T-cells from multiplying; another weakens them and shortens their life span.

Several checkpoint inhibitors have already been approved for treatment of patients with more-advanced NSCLC, based on clinical trials showing they were superior to chemotherapy,3,4,5 Keytruda  has shown prolonged survival and an increased time to cancer recurrence compared with standard chemotherapy in patients with newly diagnosed advanced NSCLC whose tumors expressed high levels of PD-L1. Patients had to have PD-L1 expression greater than 50 percent to participate in the trial.1

This is in contrast to the checkpoint inhibitor Opdivo, which, in another clinical trial in newly diagnosed patients, did not improve outcomes for PD-L1–positive NSCLC when compared with chemotherapy.6 This came as a bit of a surprise to many in the oncology community, but the results may be explained by the fact that the Opdivo trial did not require participants’ cancers to have as high a level of PD-L1 expression.

Researchers suspect that checkpoint inhibitors might work better if they are combined with treatments that kill tumor cells because debris from dead cancer cells may help the immune system recognize its target. Studies are under way to test checkpoint inhibitors in combination with chemotherapy. But it is a delicate balance to adjust the timing and doses because in addition to killing cancer cells, chemotherapy treatments can knock out the immune system just when it is needed most.

One significant side effect of checkpoint inhibitors will require further research: in addition to causing lung inflammation, checkpoint inhibitors can lead to autoimmune disease, including colitis and rheumatoid arthritis, which result from an attack on other tissues by the revved-up immune system.

More-detailed and in-depth results of the recent clinical trials evaluating checkpoint inhibitors will is forth coming, and this will provide better guidance regarding their optimal use in the treatment of NSCLC. Importantly, there are also ongoing clinical trials evaluating these and other novel targeted and immunotherapies for the management of NSCLC; patients should discuss the potential role of these trials with their treating physician.

Next: Precision Cancer Medicine for Non Small Cell Lung Cancer

References


1 Merck’s KEYTRUDA® (pembrolizumab)Demonstrates Superior Progression-Free and Overall Survival Compared to Chemotherapy as First-Line Treatment in Patients with Advanced Non-Small Cell Lung Cancer [news release]. Merck website. Available at: http://www.mercknewsroom.com/news-release/oncology-newsroom/mercks-keytruda%C2%A0pembrolizumab-demonstrates-superior-progression-free-. June 16, 2016.

2 Leighl NB, Rekhtman N, Biermann WA, et al. Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Guideline. Journal of Clinical Oncology. 2014;32(32):3673-79. Available at: http://jco.ascopubs.org/content/32/32/3673. Accessed September 30, 2016.

3 Brahmer J, Reckamp KL, Bass P, et al. Nivolumab versus docetaxel in advanced squamous-cell non–small-cell lung cancer. New England Journal of Medicine. 2015;373(2):123-35. Abstract. doi: 10.1056/NEJMoa1504627.

4 Borghaei H, Paz-Arez L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. New England Journal of Medicine. 2015;373(17):1627-39. doi: 10.1056/NEJMoa1507643.

5 Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. New England Journal of Medicine. 2015;372(21):2018-20. Abstract. doi: 10.1056/ NEJMoa1501824.

6 Bristol-Myers Squibb Announces Top-Line Results from CheckMate -026, a Phase 3 Study of Opdivo (Nivolumab) in Treatment-Naïve Patients with Advanced Non-small Cell Lung Cancer [news release]. Bristol-Myers Squibb website. Available at: http://investor.bms.com/investors/news-and-events/press-releases/press-release-details/2016/Bristol-Myers-Squibb-Announces-Top-Line-Results-from-CheckMate–026-a-Phase-3-Study-of-Opdivo-nivolumab-in-Treatment-Nave-Patients-with-Advanced-Non-Small-Cell-Lung-Cancer/default.aspx. August 5, 2016.