Medical Oncologist
When gefitinib stops working
T790M Testing After — Gefitinib Stops Working
When gefitinib stops controlling your cancer, the next step is not to give up on targeted treatment — it is to find out why the drug has stopped working. T790M testing answers that question.
Medically reviewed by Dr. Bharati Devi Gorantla, Medical Oncologist, MBBS · MD · DM (Adyar, Chennai) · ECMO · MRCP SCE (UK) · Last reviewed August 2026
- Resistance is expected — Most EGFR-mutant cancers develop resistance to gefitinib over time. Testing is the plan for that moment, not a surprise.
- T790M is the most common cause — In roughly half of cases where gefitinib has stopped working, a secondary mutation called T790M is responsible, according to ESMO.
- A blood test is usually enough — Liquid biopsy — a blood draw — can detect T790M without a second tissue biopsy in many cases.
- The result guides the next treatment — A positive T790M result opens a specific treatment pathway. A negative result redirects the plan to other options.
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When gefitinib stops controlling your cancer, T790M testing looks for the most common resistance mutation. A blood sample or repeat biopsy is sent to the laboratory, and the result — usually within one to two weeks — tells your oncologist which treatment to consider next. NCCN and ESMO both recommend T790M testing as the standard first step at progression.
Why does gefitinib stop working?
Gefitinib works by blocking an abnormal EGFR signal that some cancer cells depend on to grow. Over time, cancer cells can develop a second change in that same gene — called T790M — that makes the drug less effective.
This is a known biological process, not a sign that something went wrong with your treatment. Resistance developing after a period of control is the expected trajectory for most people on first-generation EGFR inhibitors, which is why testing at progression is built into international guidelines from NCCN and ESMO.
In roughly half of people whose gefitinib has stopped working, T790M is the cause, according to ESMO. The remainder have different resistance mechanisms that require a different approach.
What to have ready before your T790M test
- Your most recent CT scan report, so your oncologist can confirm that progression has occurred before ordering the test.
- The original pathology report showing your EGFR mutation type — the laboratory needs this context.
- A note of when you started gefitinib, what dose you are taking, and whether you have missed any doses.
- A list of any other medicines, supplements or herbal preparations you are currently taking.
- Contact details for the oncologist coordinating your care, in case the testing centre needs to share results directly.
Terms your oncologist may use
- T790M
- A secondary mutation in the EGFR gene that develops in some cancer cells after exposure to first-generation EGFR inhibitors. It is the most common reason gefitinib stops working.
- Liquid biopsy
- A blood test that detects fragments of cancer DNA circulating in the bloodstream. It is the preferred first approach to T790M testing because it is less invasive than a tissue procedure.
- Tissue re-biopsy
- A sample taken from a tumour site — typically a lymph node, a secondary deposit, or the original tumour — when the liquid biopsy result is negative or inconclusive.
- Progression
- The point at which imaging shows the cancer has grown or spread despite treatment. This is the trigger for T790M testing, not a reason to stop treatment altogether.
- Resistance
- The biological process by which cancer cells develop the ability to grow despite a drug that was previously controlling them. Testing identifies the mechanism so the next step can be targeted.
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MBBS, MD(General Medicine), DM(Medical Oncology)(Adyar,Chennai), ECMO, MRCP SCE(UK)
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What does the T790M result mean for your next treatment?
If T790M is found, the result opens a specific treatment pathway. Third-generation EGFR inhibitors are designed to work even in the presence of the T790M mutation, and your oncologist will discuss whether that pathway applies to your situation.
If T790M is not found, the resistance is coming from a different mechanism. NCCN and ESMO both recommend broader molecular profiling at this point, so that other actionable changes — some of which have their own targeted options — are not missed.
A negative result is not the end of options. It is information that tells your team where to look next.
How T790M testing happens, step by step
Progression is confirmed
Your oncologist reviews your latest CT scan or other imaging. The test is ordered when there is clear evidence that gefitinib is no longer controlling the cancer.
A blood sample is taken
A liquid biopsy is the usual first step. Blood is drawn and sent to a specialist laboratory to look for T790M in circulating tumour DNA.
Tissue re-biopsy if needed
If the liquid biopsy is negative or the result is unclear, your oncologist may arrange a sample from a tumour site. This gives the laboratory more material to work with.
Results are reviewed
The laboratory report comes back, usually within one to two weeks. Your oncologist interprets it alongside your full clinical picture.
The next plan is discussed
Your oncologist explains what the result means for your specific situation and what the recommended next step is. Bring someone with you to this appointment if you can.
What happens if T790M is not the reason gefitinib stopped working?
Roughly half of people whose gefitinib has stopped working do not have T790M. In that group, resistance has come through other changes — some of which can be identified through comprehensive molecular testing on a new tissue sample.
NCCN and ESMO both recommend looking beyond T790M at progression, because other actionable mutations — such as MET amplification or HER2 changes — are found in a meaningful proportion of these cases and have their own targeted treatment options.
A clinical trial may also be relevant at this stage. Your oncologist can tell you whether trials are currently open for your cancer type and resistance profile.
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Common questions
Frequently asked questions
How will I know when gefitinib has stopped working?
The usual sign is a CT scan showing that the cancer has grown or spread despite taking gefitinib. You may also notice a return or worsening of symptoms — breathlessness, cough, or new pain — but imaging is what confirms it. Your oncologist monitors you with regular scans throughout treatment, so progression is typically identified at a scheduled review rather than as a sudden event. If symptoms worsen between scans, contact your team rather than waiting for the next appointment.
How long does T790M testing take?
A liquid biopsy result usually takes one to two weeks from when the blood sample reaches the laboratory. A tissue re-biopsy takes slightly longer because the sample first needs to be processed before the molecular analysis begins. Ask your oncologist when the sample was dispatched and when the result is expected, so you have a clear timeline rather than an open-ended wait.
Is a blood test enough, or will I need another biopsy?
A liquid biopsy — a blood draw — is the recommended first step under NCCN and ESMO guidance, because it can detect T790M without a surgical procedure. If the blood test comes back negative, a tissue re-biopsy may be needed. A negative liquid biopsy does not completely rule out T790M — it may mean that the circulating DNA levels were too low to detect. Your oncologist will advise based on your specific result.
What if the T790M test comes back negative?
A negative result means T790M is not the reason gefitinib stopped working, and the next step is broader molecular testing to look for other resistance mechanisms. Some of these — such as MET amplification — have their own targeted treatments, so a negative T790M result is not a closed door. NCCN and ESMO both recommend comprehensive molecular profiling at progression rather than stopping at a single negative result.
Can T790M testing be arranged at CION?
Your oncologist at CION can order T790M testing and coordinate where the sample is sent. Liquid biopsy and tissue re-biopsy referrals are arranged as part of the progression assessment. The result comes back to your treating oncologist, who reviews it in the context of your full clinical picture before discussing next steps with you.
What should I ask at the appointment where progression is discussed?
Ask four things: whether T790M testing is being ordered, whether it will be a blood test or tissue biopsy and why, when the result is expected, and what the plan is for both a positive and a negative result. Having the answer to the last question before you leave means you are not waiting in uncertainty. Also ask whether comprehensive molecular profiling is being considered alongside T790M, so that other resistance mechanisms are not missed.