Why did my EGFR lung cancer stop responding to Tagrisso?

Question

Hello doctor,

I really need someone to explain what is happening because my oncologist used a lot of terms I could not fully follow during our last appointment.

I am 35, diagnosed with EGFR mutant lung cancer two years ago, and was doing really well on Osimertinib (Tagrisso). My scans were showing shrinkage, and my CEA had dropped from 89 to 12, and everyone was happy.

My last CT scan three weeks ago showed two new lesions in my right lobe, and my CEA has jumped back to 67, and my oncologist said the lung cancer has developed resistance to Tagrisso. Why did my EGFR lung cancer stop responding to Tagrisso at age 35 when I was responding so well before?

He mentioned the C797S mutation and MET amplification as possible resistance mechanisms and discussed liquid biopsy to confirm which is present. He is now suggesting either combination chemotherapy with Carboplatin and Pemetrexed or enrolling in a clinical trial for a third-generation drug.

I have a six-month-old baby at home, and my husband is working double shifts to manage everything. I am also having new bone pain in my lower back and am waiting for the bone scan results. I cannot afford for this treatment to fail. What are my actual options here?

Please guide me.

Answer 1

Hello,

Welcome to icliniq.com.

I have read your query and understand your concern.

I can understand how frightening and exhausting this must feel for you, especially when things were going well for two years, and now you are hearing about resistance and new treatment decisions while also caring for a young baby.

Many patients with epidermal growth factor receptor (EGFR)-mutated lung cancer go through a similar phase after initially responding very well to targeted therapy, so what you are describing is something doctors do see in practice.

Osimertinib works by blocking the abnormal EGFR signal that allows those cancer cells to grow. In the beginning, most of the tumor cells depend heavily on that signal, which is why your scans improved and your CEA (carcinoembryonic antigen) level dropped so much.

Over time, however, some cancer cells can develop additional genetic changes that allow them to grow despite the medicine. This is what doctors mean when they say the cancer has developed resistance. It does not mean the treatment failed suddenly or that anything was missed earlier. It simply means the cancer cells have adapted.

The mutations your doctor mentioned are some of the known ways this resistance can occur. That is why a liquid biopsy is often done. It is a blood test that looks for tumor DNA (deoxyribonucleic acid) circulating in the bloodstream and can sometimes identify the exact resistance mechanism. If a specific change is found, there may be targeted drugs or clinical trials designed to treat that particular pathway.

If testing does not show a new targetable mutation, chemotherapy with medicines like Carboplatin and Pemetrexed is commonly used at this stage. Many patients with EGFR-mutated lung cancer still respond well to this treatment after targeted therapy stops working.

Clinical trials are also an important option because several newer drugs are currently being studied specifically to overcome resistance to Osimertinib.

The bone pain you mentioned is something your doctors are appropriately investigating with a bone scan. If the cancer has involved the bone, there are treatments that can help control the disease in those areas and reduce pain, including medications that strengthen the bones and sometimes focused radiation if required.

Hope I have addressed all of your queries and concerns. Do follow up whenever needed.

Thank you.