Targeted Therapies for Lung Cancer

As I’ve previously written, the most useful biomarkers for predicting the efficacy of targeted therapy in advanced non-small cell lung cancer (NSCLC) are genomic alterations known as “driver mutations.” These gene mutations occur in cells encoded for proteins that are 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, this mutation is more common in patients with adenocarcinomas and no prior history of smoking, as well as in women and those of Asian descent.

I remember attending the American Society of Clinical Oncology (ASCO) conference in 2004 and hearing the buzz surrounding a drug called Gefitinib (Iressa). The FDA had approved Iressa in May of 2003 for treatment of 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 realized 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.

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.

Today, 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 fewer 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 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. Test results showed that he had the EGFR exon 19 mutation and his regimen was immediately changed from chemo to Tarceva. We were all blown away with how quickly he responded to the targeted treatment.  It showed me how remarkable the response was to a targeted therapy.  Every cancer patient deserves to get molecular testing to identify the best course of treatment, which may be a targeted therapy such as Tarceva.

Dave Bjork Precision Medicine Advocate

Dave Bjork Precision Medicine Advocate

Dave Bjork is a lung cancer survivor who was diagnosed when he was 34 years old. He has spent the past 15 years advocating for patient education and cancer research. He connects individuals, businesses, academic institutions and other key influencers to forge strong partnerships in the fight against cancer. Learn more about Dave.