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Home Run in Lung cancer treatment : Dr. Nilesh D. Mehta

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Lung cancer can often be a confusing topic to many. There are two major types of lung cancer: non-small cell Lung cancer ( includes sub-types of squamous cell carcinoma, adenocarcinoma, large cell carcinoma), and small cell carcinoma. Each lung cancer is treated in different ways utilizing combinations of treatment that generally include surgery, chemotherapy, radiation treatments, immunotherapy and targeted drugs. There has been a major impetus in lung cancer research over the last decade or so. The thought is to individually understand the biology of lung cancer and identify what “drives” those cancer cells. In the ideal world, lung cancer should be detected at a very early stage perhaps at stage I or a stage II which potentially would allow oncologists to cure more lung cancer patients. In the event that the cancer is diagnosed in stage III or stage IV, then additional treatments would become relevant.

In the United States, adenocarcinoma is the most common type of lung cancer, representing about 40% of all Lung cancer. Unfortunately, Lung cancer is the leading cause of cancer related deaths among both men and women and is responsible for more cancer related deaths than breast cancer, colon cancer, and prostate cancer combined. While Lung cancer is most commonly found in current or former smokers, people who have never smoked can get Lung cancer also. An estimated 15% of Lung cancer patients in the United States have never smoked. In certain parts of the world particularly in Asia, the majority of women who get lung cancer have never smoked.

This write-up is primarily to focus on the new advances in the field of non-small cell Lung cancer, an area of intense and fairly gratifying research. Once a biopsy has been performed, pathologist and oncology team will seek additional information on non-small cell Lung cancer patients to figure out if the patient has any mutations. Based on the mutations that are expressed by the tumor cells, oncologists often start treatment with an oral medication rather than the more toxic intravenous chemotherapy. It is important to realize that not all patients with non-small cell Lung cancer will have a mutation, that typically include EGFR, ALK, ROS1. At this point in time, there are oral drugs available for each of these patients who have this highly specific mutation. While these targeted drugs were being researched in patients with a specific mutation, several scientists researched our good old immune system of humans. Researchers have often felt the need to unlock the immune system mystery to assist cancer patients.

There has been a major milestone that was reached last month when immunotherapy trumped chemotherapy in lung cancer patients. Physicians wait decades sometimes for some new treatments to surface in treating patients with cancer. Historically, chemotherapy has been our mainstay of therapy for patients with stage IV lung cancer Immunotherapy is given as an intravenous solution that allows patient’s own immune system to fight cancer cells. It is almost like a self-recruitment or perhaps releasing the hand brakes for a full flowing immune system. Body’s T cells ( immune system) go into an overdrive state helping patients fight their Lung cancer.

In Demmark,at the European Society for Medical Oncology (ESMO) Congress 2016,immunotherapy with pembrolizumab (Keytruda, Merck & Co.) showed superiority over the traditional chemotherapy when used as first-line treatment of non-small cell lung cancer. Many believe that the results of this clinical trial are a home run in lung cancer treatment. To topple a well established therapy which has been utilized for decades with a non-chemotherapy treatment speaks volumes for the research effort that has gone into these compounds – immunotherapeutic agents or check point inhibitors. Speaking at the Congress, Dr. Jean Charles Soria, MD, PhD, Institut Gustave Roussy, Villejuif, France described chemotherapy as “the big gorilla.”

It is currently estimated that 20% of all non-small cell lung cancer show mutations and standard treatment would be the oral drugs that are specific targeted agents for specific mutations. Now, of the remainder 80% of the patients not displaying any mutation, approximately 30% patients have a high expression of programmed death ligand 1 (PD-L1). PD-1 pathway has been elucidated by scientists and contributes in a major way with regards to human immune responses. Cancer cells somehow figure out to curb the immune system or indirectly lessen body’s defence mechanisms.

Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has anti-cancer activity in advanced non–small cell lung cancer patients. This was particularly noticeable in patients with increased activity in tumors that express programmed death ligand 1 (PD-L1). This drug will be potentially utilized in patients with or without the mutations seen in non-small cell Lung cancer. This is cutting edge research that will transform the patient treatments in non-small cell Lung cancer patients who have metastatic or stage IV disease. While the treatment with pembrolizumab also has its own adverse effects, they are quite different than the traditional chemotherapy adverse effects. Patients would not lose their hair or experience any nausea or emesis which would mentally be of huge benefit for these patients. Since PD-L1 antibody drugs are immunotherapeutic agents, their side effects are typically related to diarrhea, potential inflammation of internal organs such as lung, colon, liver or other glandular functions which could be treated with medications.

This could represent a major paradigm shift in the management of non-small cell lung cancer patients and may have an immediate impact in patient management. Great news for our lung cancer patients and their families.

Dr. Nilesh D. Mehta