Stage IV non-small cell lung cancer may not be as “scary” as you think
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When it comes to advanced lung cancer, many patients are afraid to talk about it and feel that there is no hope. In fact, with the development of science, the technology for treatment of advanced lung cancer is rapidly evolving, with a wide range of treatments such as targeted, immune, anti-angiogenic, and chemotherapy.
How to live in harmony with advanced lung cancer? Can we achieve maximum benefit by combining different treatments, buy more time, and wait for the opportunity to receive more new therapies?
The answer is yes. In this article, let’s take a look at one of the best tips for advanced non-small cell lung cancer (NSCLC) treatment: targeted therapy, through Mr. Zhou’s story.
First encounter – gentle targeted drugs
In the winter of 2013, Mr. Zhou had a chest X-ray at a local hospital because he always had a dry cough, and a mass of about 5 cm was found in his right lung. He came to the Guangdong Lung Cancer Institute and underwent PET-CT, which revealed that the tumor had metastasized to the thoracic spine and liver and was diagnosed as advanced lung cancer.
On the advice of his primary care physician, Mr. Zhou underwent a lung puncture biopsy and had tumor tissue taken for pathology, which was found to be adenocarcinoma.
Adenocarcinoma of the lung is a common type of NSCLC, mostly seen in patients who do not smoke. After the diagnosis of lung adenocarcinoma, the primary care physician recommended genetic testing of the tumor tissue to determine if there are variants in genes such as EGFR, ALK, and ROS1. The reason for this is that these genetic variants are closely related to the development of lung cancer and are called the “driver genes” of lung cancer.
Non-smoking women with lung cancer have a high prevalence of EGFR mutations, and once they are detected, it is a “stroke of luck”. The reason is that targeted drugs for EGFR mutations are like the blood pressure medications that older people take today, and they are effective with fewer side effects than traditional chemotherapy, which is typically a gentle girl.
Mr. Zhou was fortunate to have a “positive” EGFR gene mutation and met this “gentle girl”, the first-generation EGFR-targeting drug gefitinib. One week after taking the drug, his dry cough improved significantly, and two months after taking the drug, a follow-up CT showed a 31% reduction in tumor size! He returned to work with no discomfort other than a mild rash while on the drug.
Day by day – targeted love has its bumps and bruises
In the blink of an eye, Mr. Zhou has been taking gefitinib for 22 months. Recently, he felt his cough had worsened, and a review revealed that his lung tumor was significantly larger than before. He approached his primary care physician again with anxiety and was evaluated and determined to be resistant to gefitinib, which is a “hurdle” that patients taking targeted drugs have to go through sooner or later.
The doctor recommended another biopsy of his tumor tissue and a blood test for EGFR gene variants.
Why another puncture biopsy? The doctor told Mr. Zhou that T790M mutations are detected in about 50% to 60% of patients taking a generation of EGFR-targeted drugs after resistance occurs, which is often the cause of drug resistance. Simply put, targeted therapies need to “find the right bullseye” in order to work, and once the bullseye changes, it will naturally fail. The good news is that we now have a “nemesis” for the T790M mutation in the EGFR gene – a third-generation EGFR-targeting drug.
There are other reasons for resistance in some patients, such as MET amplification, small cell transformation, and so on, which require going back to the source and finding the right new drug to deal with.
Mr. Zhou couldn’t help but feel that for EGFR mutation-positive lung cancer, the process of using a generation of drugs is like first love, but it can go wrong after a long time, and it’s time not to blindly start the next relationship, but to first figure out what kind of girl is right for you. The first step is to take another tumor biopsy and do genetic testing to help us find the right drug to start the next “targeted love”.
Hua Ming – Meeting the third generation of EGFR-targeted drugs
Mr. Zhou first had his blood tested for EGFR mutations, and no T790M mutation was found, but his primary care physician said, “This ‘negative’ result could be ‘false’. The tumor may be releasing a low amount of DNA into the bloodstream, or the test may not be sensitive enough to get a more reliable result by taking tumor tissue.”
On the advice of his doctor, Mr. Zhou underwent another puncture biopsy of his lung tumor, and the pathology results 1 day later confirmed that the type of pathology was still adenocarcinoma, while the genetic test 4 days later found an EGFR T790M mutation.
At that time, the hospital was conducting a clinical study of the third-generation EGFR-targeted drug, ivitinib. The company’s main goal is to provide the best possible service to its customers. After 1 week of taking the drug, the “miraculous” effect reappeared, his dry cough improved significantly, and a month later the tumor shrank by 25%.
The future – trust and confidence
Time is running out, and Mr. Zhou has been in treatment for more than 4 years. He has experienced the confusion and anxiety of his initial diagnosis, the surprising efficacy of targeted drugs, and the stumbling of targeted therapy resistance. But with the belief of living in harmony with lung cancer for a long time, he believed in his doctors and seized the opportunity in time to start his second targeted love through clinical research. In the blink of an eye, he persisted for another year or so. What if drug resistance occurs again in the future? This concern of Mr. Zhou is also the concern of many patients.
Believe it or not, research on targeted drugs is advancing rapidly, and many drugs that are not yet on the market are “reaching” some of the lucky ones through clinical studies, and more and more patients with advanced disease are expected to have a “love affair” with targeted therapy.
In this race against the disease, it is possible to control lung cancer as a “chronic disease” at the right time (timely drug resistance gene testing), in the right place (maintaining close long-term follow-up in the same hospital), and with the right targeted drug (choosing the right drug for the gene variant or joining a clinical study).
Disclaimer:
Tumors are extremely complex and treatment options are highly individualized, and this case does not represent a treatment decision for a “similar patient. Please seek professional advice from your supervising physician regarding your specific treatment plan.
Co-authors: Dr. Bai Xiaoyan Dr. Zhang Yichen, Guangdong Provincial People’s Hospital, Guangdong Lung Cancer Institute