Monday, January 16, 2017

Targeting Mutations in Lung Cancer: EGFR

As I’ve previously written, the most useful biomarkers for predicting the efficacy of targeted therapy in advanced NSCLC are genomic alterations known as "driver mutations." These mutations occur in cancer cells within genes encoding for proteins critical to cell growth and survival. Through the use of molecular testing, the discovery of genetic mutations that drive NSCLC is rapidly improving the outlook for some patients in stage 4 disease. This is significant because almost 40% of lung cancer diagnoses are stage 4 patients. One of the first breakthroughs was the discovery of the EGFR (epidermal growth factor receptor) mutation, which is present in about 10 percent of patients who are diagnosed with lung cancer in the United States (interestingly more common in patients with adenocarcinomas and no prior history of smoking, as well as in women and those of Asian descent).

I remember being at the American Society of Clinical Oncology (ASCO) conference in 2004 and the buzz surrounding a drug called Gefitinib (Iressa). The FDA had approved Iressa in May of 2003 for treatment of Non-Small Cell Lung Cancer (NSCLC) and it was notable that in clinical trials the drug worked spectacularly well in about 10% of lung cancers patients but failed to help the rest. No one could figure out why. Then researchers figured out that most people who responded to Iressa had similar genetic mutations in their tumors. A later study extended the findings in EGFR research to a related drug, Tarceva, which was awaiting approval by the FDA.
The two groups of Harvard researchers, one at Massachusetts General Hospital (MGH) and one at Dana Farber Cancer Institute did a deep dive into the data regarding lung tumors from patients who responded to Iressa and those who did not. Most responders had the EGFR mutations. Non-responders did not. The laboratories began offering a test to detect the mutations and scientists speculated they could become widely available in the near future. MGH had a clinical trial that was testing patients for the mutations as a predictor of their response to Iressa as an initial treatment. Iressa wasn’t usually the first option; it was typically given to lung cancer patients who didn’t respond to chemotherapy. Now that scientists could explain the drug’s effectiveness in some cases, there was hope that they could better predict who would respond to them in the future and that lessons from Iressa and Tarceva could be applied to other cancers. This is when targeted therapy began to become a reality.
Iressa and Tarceva are part of a relatively new class of drugs known as targeted drugs, which are different from traditional chemotherapy drugs because they are designed to specifically hit cancer cells. Unlike chemotherapy drugs which kill healthy and cancerous cells, targeted drugs are supposed to kill only cancer cells. Until the mid-2000’s, treatment options for lung cancer were mostly limited to surgery, chemotherapy and radiation. Now, people diagnosed with lung cancer have newer, more personalized treatment options. The goal of targeted therapy is to accurately target your individual tumor, which hopefully leads to more effective treatments and less side effects.
Thankfully screening has become an increasingly standard part of the diagnostic work-up for NSCLC, and is useful in choosing between standard chemotherapy and targeted therapies. EGFR-targeting drugs — which include Tarceva (erlotinib), Iressa (gefitinib) and Gilotrif (afatinib) — are now used in the first-line treatment for metastatic lung cancer patients. Patients are able to get a treatment that matches the mutation that has been identified through a molecular test of their tumor. While most lung cancer patients with EGFR mutations who respond well to targeted treatments ultimately develop resistance to the drugs after a year or so as the cancer finds other ways to grow, newer drugs are being evaluated to be used as second-line treatments. This is why it’s important to have tumors continuously tested during treatment to detect different mutations that evolve during treatment. For example, Tagrisso (osimertinib) is approved for patients with a specific EGFR mutation called T790M who relapse after being treated with a different EGFR drug. A similar drug called rociletinib (CO-1686) is in late-stage trials in patients with the T790M resistance mutation.
I saw first-hand this process of genetic testing, and the resulting treatment when a good friend of mine was diagnosed with stage 4 lung cancer. He went to the hospital and started chemotherapy treatment. Within 24 hours he was on a ventilator fighting for his life and not responding to the chemo. Test results showed that he had the EGFR exon 19 mutation and his regimen was immediately changed from chemo to Tarceva. He started responding and was off the ventilator breathing on his own within 2 days. We were all blown away with how quickly he responded to the targeted treatment. While unfortunately in his case it was too late to save his life, it did show me how remarkable the response was to a targeted therapy. It also convinced me that every cancer patient deserves to get molecular testing to identify the best course of treatment, which may be a targeted therapy such as Tarceva.
#CancerResearchEvangelist
#PrecisionMedicine

5 comments:

  1. ALL THANKS TO DR WILLIAMS WITH HIS HERBAL PORTION I WAS COMPLETELY CURED FROM BREAST CANCER.
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    1. Glory be the Name of the( LORD JESUS)
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  4. Hello everyone am here to share my testimony. I was suffering from BREAST CANCER for the past 3 years and my Dr told me that there is nothing he could do, after the 5 times chemotherapy and radiation and i was not responding to treatment and not even getting better and i had no money for Surgery because it was too expensive for me. I was frustrated and confused, seeking advice from people until a friend told me about Dr. Osebulu Herbal Medicine and herbal cannabis oil and its fast curing ability of any kind of cancer and told me that her mother's LUNGS CANCER was cured by the same Doctor Osebulu. I was desperate to to have the HERBS and i contacted Dr. Osebulu via email to get the miraculous oil. The Dr send me the Herbal Medicine and Cannabis oil through FedEx, to cut the long story short, i got Completely Cured after taking the Herbs for a week. To cut the long story short, as i am writing this testimony on this Blog am so strong and healthy no more cancer in my body again. I did my test and the Doctor confirmed it, i do not have BREAST CANCER anymore which he (The Medical Doctor) was Shock when he confirmed it. I really want to Appreciate Dr Osebulu who got me cured with the help of his herbal medicine and to God Be All The Glory.

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