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New Directions in Lung Cancer

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Lung cancer treatment is changing, thanks to research in prevention, early detection and treatment. Recent advances include new ways to operate on lung cancer, improvements in radiation techniques and the approval of new therapies that target a specific feature of the cancer and activate the immune system against the cancer. These are some of the current major areas of research in lung cancer:

Targeted Therapies

The area of personalized medicine in cancer and the role that targeted therapies play is one of the most active areas of research in lung cancer. While several targeted therapies have already been approved for use in lung cancer (see Targeted Therapies), many more have been identified as possible treatments and are being tested in clinical trials. 

  • Necitumumab is designed to target the EGFR mutation and is showing promise in the treatment of advanced squamous cell carcinoma, a type of NSCLC.  
  • Dabrafenib (Tafinlar) is a kinase inhibitor, currently approved for the treatment of melanoma that contains the BRAF V600E mutation and cannot be removed by surgery or has spread. Based on phase II clinical trial results, it received Breakthrough Therapy* designation in January 2014 for people who have been diagnosed with non-small cell lung cancer (NSCLC) that has the mutation and who have received at least one previous course of chemotherapy.
  • Cetuximab (Erbitux) is a monoclonal antibody and an epidermal growth factor receptor (EGFR) inhibitor. Study results released in June 2008 showed a small but real increase in survival in NSCLC patients (including squamous cell carcinoma) who were treated with a combination of drugs including Cetuximab. In January 2009, the FDA application submitted to approve Erbitux as a treatment for advanced NSCLC was withdrawn because of potential differences in the drug formula within the US compared to what was available outside of the US in clinical trials. The application for approval is expected to be resubmitted.

Unfortunately, cancer always finds a way to get around targeted therapies and they eventually stop working. Research efforts are underway to find new treatments to overcome this "resistance." Two drugs in particular show promise and are expected to be FDA approved in 2015:

  • AZ-9291 and rociletinib both work against EGFR to overcome the most common way that cancer develops resistance to those targeted therapies. Both drugs act on T790M, a mutation that EGFR positive cancer often develops after being treated with Tarceva (erlotinib) or Iressa (gefitinib).

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Immunotherapies

Immunotherapy is another promising area of lung cancer research. Immunotherapies increase the body’s natural defenses to attack cancer, to fight and target disease and to improve and restore function to the immune system. Several approaches being studied in lung cancer: 

Checkpoint inhibitors

The immune system is kept under control by “checkpoints.” Cancer cells can fool the checkpoints so that it can do what it wants without being slowed down or stopped. Checkpoint inhibitors work to fix the problem so that the immune system can work against the cancer. The fix on the checkpoint may turn it on to work against the cancer or it may turn off the checkpoint so the cancer can’t get through without being caught. Of particular interest is a pathway called PD-1 (programmed death 1). PD-1 is normally used by the body as a “checkpoint” that prevents the immune system from attacking normal cells; however, cancer cells are often able to make proteins that bind PD-1 to keep the immune cells ‘off’. Drugs to keep these immune cells in their active ‘on’ state so that the body will fight the tumor have been approved (see Immunotherapies) and are under investigation.  

Monoclonal antibodies

Antibodies are proteins produced in blood to fight toxins or foreign substances in the body. To treat cancer, the cancer cells that grow and spread out of control are foreign substances to target. Monoclonal antibodies (mAbs) are manmade and designed to work with those the body creates naturally to help the immune system fight and shut down the growth of the cancer. They can be used alone or with other drugs to target defects in the cancer cells or to make the cancer cells more receptive to the body’s immune system. Monoclonal antibodies can also carry other drugs or substances directly to the cancer.

  • Keytruda (pembrolizumab) is a mAb and checkpoint inhibitor that targets the PD-1 pathway. It is expected to be approved in 2015 to treat NSCLC lung cancer that does not have the EGFR mutation or the anaplastic lymphoma kinase (ALK) rearrangement and that has grown or spread while on or after treatment with a platinum-based chemotherapy like cisplatin or carboplatin. It is already approved to treat melanoma and received Breakthrough Therapy* designation for lung cancer in October 2014. 
  • Yervoy (ipilumimab) is another mAb and checkpoint inhibitor. It targets a checkpoint called CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and may be especially effective in combination with therapies that target PD1. 

Vaccines

There are two types of cancer vaccines: prophylactic vaccines which prevent cancer and therapeutic vaccines which are used to treat cancer or to prevent recurrence. In lung cancer, prophylactic vaccines have not been a focus of research. Trials involving vaccines to prevent lung cancer from coming back have yet to show they are effective, however a wide variety of approaches to help make the immune system work against lung cancer are being tested. Some include activating the immune system against particular proteins found on cancer cells. Other approaches target one or more specific antigens, the toxins or other substances that cause the immune system to act in the body. 

Vaccine updates: In March 2014, Mage A3 ASCI (Antigen-Specific Cancer Immunotherapeutic) failed to significantly extend disease-free survival compared to placebo, in either the overall MAGE-A3 (a specific tumour antigen) positive population or in MAGE-A3-positive patients who did not receive chemotherapy. In February 2013, the Lucanix trial was closed because it was not on track to meet its primary endpoint and in December 2012, the Stimuvax trial was closed because it did not meet its primary endpoint. Vaccines for lung cancer continue to be tested in clinical trials.  

*FDA Breakthrough Therapy designation was enacted in 2012 and includes all the features of Fast Track designation (given to fast track drugs that may treat serious or life-threatening illnesses, address an unmet medical need or make a positive advancement in safet or effectiveness over existing drugs) but includes more intensive guidance from the FDA on the drug's clinical development program. 

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Chemotherapies

While much research is focusing on developing novel approaches to lung cancer treatment in the form of targeted therapies and immunotherapies, research is ongoing into new chemotherapies or improvements on existing chemotherapies.

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Maintenance Therapies

While several drugs have been approved for use or are commonly used as maintenance therapy, oncologists do not fully agree on whether it is always the best option. Research is continuing to test maintenance therapies in an effort to better identify patients who will benefit from them.

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Chemoprevention

While important research is going on in the treatment and diagnosis of lung cancer, another area of research is in chemoprevention, or the use of substances to prevent lung cancer from developing. This research has many challenges, and so far researchers have had mixed results come from their studies. Current research is focusing on drugs that have been approved for treatment in other conditions but that potentially decrease risk of lung cancer. 

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Early Detection

Access to quality screening for those at high risk for lung cancer is becoming common place all over the United States. You can find information on screening here and help finding a center of excellence near you here. Several other approaches are being explored to detect and screen for lung cancer, including blood tests, breath tests, sputum cytology and cell sampling from airway via bronchoscopy. While these are still in the research phase, these kinds of tests may one day be widely available. 

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