What to Do After Ibrance Stops Working for Metastatic Breast Cancer

Understanding How Ibrance Works for Metastatic Breast Cancer

Ibrance (palbociclib) is an oral targeted therapy drug used to treat hormone receptor-positive, HER2-negative metastatic breast cancer. It is often prescribed in combination with other hormonal therapies like letrozole or fulvestrant.

Ibrance works by inhibiting proteins called cyclin-dependent kinases 4 and 6 (CDK 4/6). These proteins regulate the cell cycle and division of cancer cells. By inhibiting CDK 4/6, Ibrance can help slow or stop the growth of cancer cells.

For many patients, taking Ibrance helps control metastatic breast cancer for a period of time. However, eventually the cancer cells may stop responding to treatment with Ibrance. This is known as cancer progression.

Why Does Ibrance Stop Working?

There are a few reasons why Ibrance may stop controlling metastatic breast cancer after a period of time:

• The cancer cells develop resistance - They find ways to bypass the drug's mechanism of action
• The cancer cells activate alternate cell proliferation pathways not impacted by Ibrance
• The cancer cells mutate and no longer rely on CDK 4/6 activity

Most patients take Ibrance for somewhere between 1-3 years before cancer progression is detected. But this timeframe can vary substantially between patients.

Monitoring Disease Progression on Ibrance

While on Ibrance, patients should have regular scans (typically CT, bone scan, PET scan) every 2-3 months to monitor the disease. Blood tumor marker tests like CA 27.29 may also be checked.

If several consecutive scans show disease progression, it likely means Ibrance has stopped working. Some signs of progression include:

• New lesions in bones, lungs, liver or other areas
• Significant growth in pre-existing tumors
• Rising tumor marker levels

Patients who have taken Ibrance for over a year with no signs of progression may be considered to have an exceptional response. But eventually, the cancer cells will find ways to bypass Ibrance's effects.

Treatment Options After Ibrance Stops Working

If you have metastatic breast cancer and Ibrance has stopped keeping it in check, don't lose hope. There are still many treatment options to help extend and improve your quality of life.

Other CDK4/6 Inhibitors

Recently, two other CDK 4/6 inhibiting drugs similar to Ibrance have been approved:

• Kisqali (ribociclib) - FDA approved in 2017 for HR+/HER2- breast cancer
• Verzenio (abemaciclib) - FDA approved in 2017 for HR+/HER2- breast cancer

Studies have found these drugs to be effective after Ibrance stops working. The drugs have similar mechanisms but are not identical, so cancer cells may still respond.

Your oncologist can prescribe Kisqali or Verzenio in combination with an aromatase inhibitor or other hormone therapy after progression on Ibrance.

Hormone Therapies

There are also other hormone therapy options if cancer cells are still HR+ after Ibrance. These include:

• Aromatase inhibitors like letrozole (Femara) or exemestane (Aromasin)
• Estrogen receptor antagonists like fulvestrant (Faslodex)
• Estrogen receptor downregulators like lasofoxifene (Fablyn)
• Progestins like megestrol acetate (Megace)

A trial of a different hormonal drug or combination may help control cancer growth for some time.

Chemotherapy

Traditional chemotherapy is still used to treat metastatic breast cancer. It can reduce tumor size and help control symptoms.

Options like paclitaxel, docetaxel, capecitabine, gemcitabine and others may provide benefit after Ibrance stops working. Chemotherapy is typically given for several months at a time.

PARP Inhibitors

PARP inhibitors like Lynparza (olaparib) and Talzenna (talazoparib) can be used to treat HER2-negative metastatic breast cancer. They work by blocking enzymes involved in DNA damage repair.

Studies show PARP inhibitors provide clinical benefit after CDK4/6 inhibitors stop working. They are given orally on a continuous basis.

Immunotherapies

Immunotherapy harnesses the power of the immune system to fight cancer. The FDA has approved some immunotherapies for certain types of breast cancer:

• Keytruda (pembrolizumab) - Approved for PD-L1 positive triple negative breast cancer
• Tecentriq (atezolizumab) - Approved with chemotherapy for PD-L1 positive triple negative breast cancer

Clinical trials are also looking at using immunotherapy after CDK4/6 inhibitors stop working. This approach may become more common in the future.

Targeted Therapies

In addition to CDK4/6 inhibitors, researchers have identified other molecular targets involved in breast cancer growth:

• PI3K/AKT/mTOR pathway proteins
• Cell cycle proteins like aurora kinases
• Angiogenesis proteins like VEGFR
• DNA damage repair proteins beyond PARP

Newer targeted drugs that hit these targets are becoming available through clinical trials. Some like alpelisib (Piqray) are already FDA-approved. Targeted therapy based on genetic testing of your tumor may be an option after Ibrance if your cancer has certain mutations.

Supportive and Palliative Care

Supportive care helps improve quality of life and manage cancer symptoms. Palliative care provides relief from pain, nausea, fatigue and other issues. These remain important even when Ibrance stops working.

Your oncologist, palliative care team and other specialists can help develop a supportive care plan during all stages of treatment.

The Takeaway

Metastatic breast cancer treatment has made major advances in recent years. While no drug provides a cure, new therapies offer years of extra life.

If you have taken Ibrance for an extended time but now show progression, don't lose hope. Other options like Kisqali, Verzenio, hormonal drugs, chemotherapy, PARP inhibitors and immunotherapies may help control disease.

Working closely with your care team can help maximize quality of life and longevity even after Ibrance stops working.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult with a healthcare professional before starting any new treatment regimen.