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Defactinib Fails Again as a Maintenance Therapy for Mesothelioma

patient chemotherapy for mesotheliomaThere has been another setback for a drug that showed promise as a maintenance therapy for mesothelioma.

Defactinib is a focal adhesion kinase (FAK) inhibitor. FAK is a signaling pathway that allows stem cells to give rise to new cancer cells. The developers of defactinib hoped that FAK inhibition would help keep mesothelioma tumors from growing back after chemotherapy.

But a team of international researchers has once again concluded that the drug does not work as a maintenance therapy for mesothelioma.

In Search of a Maintenance Therapy for Mesothelioma

Malignant pleural mesothelioma is an aggressive cancer that is very hard to treat.

Standard chemotherapy drugs like pemetrexed, cisplatin, gemcitabine and vinorelbine can sometimes shrink tumors, but they usually come back. Doctors have no good options for keeping mesothelioma at bay after chemotherapy ends.

Some studies suggest that pemetrexed (Alimta) can help. But there are problems with this approach, including the risk for serious side effects.

Scientists around the world are searching for other approaches to maintenance therapy for mesothelioma.

Defactinib’s Rocky Path in Mesothelioma Treatment

Defactinib had been the leading compound for Boston-based Verastem.

But in 2015, a clinical trial of defactinib maintenance therapy for mesothelioma had to stop early. Researchers determined that single-agent defactinib did not help.  

Then researchers saw another possibility.

Laboratory studies suggest that inhibiting FAK can selectively kill mesothelioma cells that have low levels of the protein “merlin”. The hope was that defactinib might help these patients, even if it could not help other mesothelioma patients.

The new trial tested defactinib in relapsed mesothelioma patients whose cells express low levels of merlin.

The trial included 344 mesothelioma patients with low merlin levels whose disease came back after at least four cycles of chemotherapy. One group of patients received oral defactinib while the other got a placebo. Neither doctors nor patients knew which group was which.

Disappointing Results for Maintenance Therapy for Mesothelioma

Once again, the results for defactinib as a maintenance therapy for mesothelioma were not good.

In patients on defactinib, it took 4.1 months for cancer to come back. It was 4 months for patients on placebo. The defactinib group lived for a median of 12.7 months. The placebo had an overall survival of 13.6 months.

“Neither PFS [progression-free survival] nor OS [overall survival] was improved by defactinib after first-line chemotherapy in patients with merlin-low MPM [malignant pleural mesothelioma],” concludes the report in the Journal of Clinical Oncology. “Defactinib cannot be recommended as maintenance therapy for advanced mesothelioma.”

Defactinib is still being studied in combination with immunotherapy as a mesothelioma treatment.


Fennell, DA, et al, “Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND-A Double-Blind, Randomized, Phase II Study.”, February 20, 2019, Journal of Clinical Oncology, Epub ahead of print, http://ascopubs.org/doi/10.1200/JCO.2018.79.0543

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