Targeted cancer medicines such as osimertinib (Tagrisso), palbociclib (Ibrance), imatinib and enzalutamide (Xtandi) can keep a cancer under control for a long time. But for many people there comes a point when the cancer starts to grow again. Hearing that your medicine has “stopped working” is hard news. This guide explains what it means, why it happens, and how doctors decide what to do next.
What “stopped working” means
Doctors usually find out from one or more of these:
- Scans that show the cancer has grown or spread (often called progression).
- Blood tests. In prostate cancer, for example, a rising PSA level can be a sign the cancer has started growing again or become resistant to treatment9. In blood cancers such as chronic myeloid leukaemia (CML), blood and bone marrow tests can show the leukaemia cells increasing again5.
- Symptoms that return or get worse.
One result on its own does not always mean the treatment has failed. A single PSA change, for example, does not always reflect how well a treatment is working for you9. Your team will look at the whole picture before making a change.
Why it happens: resistance
Cancer cells can become resistant to targeted medicines in two main ways1:
- The target changes. A new change (mutation) in the protein the medicine was aimed at means the medicine can no longer attach to it properly.
- The cancer finds another route. The cells switch to a different way of growing that does not depend on the target.
This is not your fault, and it does not mean you took the medicine wrongly. It is a known limit of targeted treatment, and it is one reason targeted medicines are often combined with other treatments1.
Tests that guide the next step
Because the cancer’s genes can change over time, a test done when you were first diagnosed may not show what is driving the cancer now. Your doctor may want to test again when the cancer grows2. The sample can come from:
- A new biopsy of the tumour2.
- A liquid biopsy, which looks for cancer DNA in a blood sample. It can be useful when the tumour is hard to reach with a needle2.
The lab report lists the changes found in the cancer and any treatments that might work for them2. A well-known example comes from lung cancer: osimertinib is licensed for lung cancer with an EGFR change called T790M that has grown on or after an earlier EGFR tablet, and this change is found by testing3. Our guide to osimertinib and T790M resistance explains this in more detail.
Typical next options, by cancer
These are the general principles. The right choice for you depends on your cancer, your earlier treatment, your test results and your health, so treat this as background for a talk with your oncologist, not a plan.
EGFR-positive lung cancer (osimertinib)
For lung cancer that grows after earlier treatment, options may include chemotherapy, targeted therapy with or without chemotherapy, and immunotherapy4. Which targeted medicine, if any, depends on what the new tests find2. See also our generic Tagrisso page.
Chronic myeloid leukaemia (imatinib)
Several tyrosine kinase inhibitors are used for CML, including imatinib, dasatinib, nilotinib, bosutinib and asciminib5. If the leukaemia comes back after a response, treatment may include ponatinib or asciminib5. Gene tests matter here too: asciminib, for example, is licensed for CML with a specific change called T315I6. See our guide to how imatinib works.
HR-positive breast cancer (palbociclib and other CDK4/6 inhibitors)
When breast cancer grows on a CDK4/6 inhibitor and hormone therapy, the team may test the cancer’s genes. Some changes open up specific options: palbociclib is licensed with inavolisib and fulvestrant for cancers with a PIK3CA change, and abemaciclib with imlunestrant for cancers with an ESR1 change78. Other options can include a different hormone therapy or chemotherapy. See our guide to Ibrance, Kisqali and Verzenio.
Prostate cancer (abiraterone and enzalutamide)
Abiraterone and enzalutamide both work on the testosterone pathway, and there is evidence of cross-resistance between them. In general, later treatments tend to help less than earlier ones10. Other options for prostate cancer that has stopped responding to hormone treatment include chemotherapy (docetaxel or cabazitaxel), radiation-based medicines and, for cancers with certain gene changes, PARP inhibitors9. See our guide to abiraterone vs enzalutamide.
Chronic lymphocytic leukaemia (ibrutinib and venetoclax)
For CLL that comes back or stops responding, options include a BTK inhibitor (such as ibrutinib, acalabrutinib or zanubrutinib), venetoclax with or without an antibody, other targeted drugs, chemotherapy, and in some cases a stem cell transplant or a clinical trial of CAR T-cell therapy11. See our guide to venetoclax in CLL.
Clinical trials
Clinical trials test new ways to treat cancer and to manage its side effects12. When a medicine stops working, a trial may give you access to a newer treatment. It is worth asking your team about trials whenever you discuss your next options12.
Questions to ask your oncologist
- What do my scans or blood tests show, and how sure are we that the medicine has stopped working?
- Should my cancer be tested again, and would a biopsy or a blood test (liquid biopsy) be better for me?
- What are my options now, and what are the side effects of each?
- Is there a clinical trial I could join?
- Should I keep taking my current medicine until the next one starts?
The practical side: cost and access
The next medicine may be more expensive than the last, or not funded where you live. Generic versions of many targeted medicines contain the same active ingredients as the original brands. Our pages on generic Ibrance, generic Xtandi, generic Imbruvica and generic Venclexta explain the options, and our cancer medicines section lists what we supply. Any change of medicine should be decided with your oncologist, and all of these need a prescription.
Medicines mentioned in this guide that we supply include Osimert 80 mg (osimertinib), Ibrance 125 mg (palbociclib), Enzamide 40 mg (enzalutamide) and Imbruvica 140 mg (ibrutinib). All need a prescription.
Frequently asked questions
What happens when Tagrisso stops working?
Your team will usually look at your scans and may test the cancer again, with a biopsy or a blood test. Depending on the results, options can include chemotherapy, a different targeted medicine with or without chemotherapy, immunotherapy, or a clinical trial.
How long does Ibrance work?
It varies from person to person, and no one can say in advance how long it will keep a particular cancer under control. It is usually continued for as long as it is working and the side effects are manageable, with regular scans to check.
What comes after abiraterone?
It depends on your earlier treatment and test results. Options can include chemotherapy, radiation-based medicines, PARP inhibitors for cancers with certain gene changes, or a clinical trial. Switching to enzalutamide may help less, because the two work in a similar way.
Does a medicine stopping working mean I did something wrong?
No. Cancer cells can change over time and find ways around a targeted medicine. It is a known limit of these treatments, not a sign that you took the medicine wrongly.
Should I stop my tablets if I think they have stopped working?
No. Keep taking your medicine as prescribed until your oncologist tells you to change. Your team may want you to continue until the next treatment is ready.
Sources & references
- National Cancer Institute. Targeted Therapy to Treat Cancer. Updated 31 May 2022.
- National Cancer Institute. Biomarker Testing for Cancer Treatment. Updated 14 December 2021.
- US National Library of Medicine, DailyMed. Tagrisso (osimertinib) prescribing information.
- National Cancer Institute. Non-Small Cell Lung Cancer Treatment (PDQ), Patient Version. Updated 16 May 2025.
- National Cancer Institute. Chronic Myeloid Leukemia Treatment (PDQ), Patient Version. Updated 9 April 2025.
- US National Library of Medicine, DailyMed. Scemblix (asciminib) prescribing information.
- US National Library of Medicine, DailyMed. Ibrance (palbociclib) tablets prescribing information.
- US National Library of Medicine, DailyMed. Verzenio (abemaciclib) prescribing information.
- National Cancer Institute. Hormone Therapy for Prostate Cancer. Reviewed 4 October 2024.
- European Association of Urology. EAU Guidelines on Prostate Cancer: Treatment.
- National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ), Patient Version. Updated 15 October 2024.
- National Cancer Institute. What Are Clinical Trials? Updated 3 November 2024.
Related reading
- CML treatment: imatinib vs dasatinib vs nilotinib
- PARP inhibitors: olaparib vs niraparib
- Ibrutinib vs acalabrutinib for CLL
- Lenalidomide in myeloma
- Cancer medicines: how oncology drugs work
- Is it chemotherapy?
- Abiraterone vs enzalutamide
This content is for informational purposes only and is not medical advice. Decisions about changing cancer treatment should be made with your oncologist. Do not stop or change any medicine on your own. Used as prescribed by a licensed medical professional.
Sangeeta Shukla is a licensed clinical pharmacist with 19 years of experience. She holds a B.Pharm and M.Pharm from Zaporozhye State Medical University. At OnlineMeds, she reviews medicine and health content to help ensure it is accurate, evidence-based, and easy to understand.