Maintenance therapy with cancer drug defactinib did not boost survival rates after front line chemotherapy for patients with pleural mesothelioma, according to the latest results from this phase II COMMAND trial.
The researchers wrote in their report released June 15 that defactinib is not recommended as potential maintenance therapy for malignant pleural mesothelioma in the advanced stages.
With few treatment options for pleural mesothelioma, which is incurable cancer caused by asbestos exposure, combined therapy with cisplatin and pemetrexed is the only effective, front line therapy for such patients. But the degree of efficacy with that chemotherapy regimen is quite limited. There are no approved maintenance treatments or therapies approved when mesothelioma progresses.
Precision and targeted cancer therapies continue to improve in treating many forms of cancer, these therapies are currently underexplored for those with pleural mesothelioma, according to the authors of the study.
Merlin-low is an expression common in pleural mesothelioma cases that is related to a higher sensitivity to FAK inhibitors, including defactinib.
So the clinical researchers did the global, double-blind, randomized, placebo-controlled COMMAND trial to review the efficacy of defactinib in 345 patient with merlin low pleural mesothelioma as possible maintenance therapy after four cycles of first-line chemotherapy.
Progression-free survival or the length of time from treatment to the disease getting worse – and the overall survival rate was the clinical study’s major primary endpoints. Quality of life also was measured.
Patients were randomized one to one to get oral defactinib (172 patients) or placebo (170 patients) until the disease progressed, there was high toxicity or withdrawal happened. There were 72 patients in the defactinib arm and 71 in the placebo arm that was thought to be merlin low.
Most of the patients – 68% – were men and their median age was 68.
Median progression-free survival was four months with defactinib, compared to four months with the placebo. It was 4.5 and 2.8 months for patients with merlin high and merlin low disease in the treatment arm.
Overall rates of survival were better with patients who got the placebo than those who got the FAK inhibitor – 13.6 months compared to 12.7 months. Also, for people who had the merlin low disease, the median rate of survival was nine months in the group with defactinib and 9.5 months in the placebo group.
Generally, there was no statistical significance seen between the arms regarding response rate, progression-free survival, overall survival rate and life quality for those with merlin-low malignant pleural mesothelioma.
The most common reason for stopping the study drug was the progression of the disease – 62%. The clinical study was closed after the first analysis by the IRB.
The most common side effects of the study drug were nausea, diarrhea, fatigue, dyspnea, and reduced appetite.
Several clinical trials are continuing to look at treatment options for mesothelioma patients. The researchers noted that molecularly stratified therapy for mesothelioma is a possibly promising approach to better outcomes for this cancer, but this sort of approach is only starting to be studied.
Overview of Treatment Options for Mesothelioma
After you have been diagnosed with mesothelioma and been tested, you will need to develop a treatment plan with your doctors. The medical team that will you with your treatment plan usually consist of:
- Social workers
The major treatment options for mesothelioma today are:
- Surgery: The aim is to take out as much of cancer as possible when it is diagnosed in the early stages. Surgery also can be an option for palliative care for a late-stage diagnosis to reduce pain by targeting the build-up of fluid in the pleural area.
- Chemotherapy: It is used to reduce the size of mesothelioma tumors or to kill any cancer cells that are left. These drugs can be used alone or can be used in a multimodal treatment plan.
- Radiation: Specifically targets mesothelioma cancer cells and prevents reproduction. Radiation is often recommended for people who are in very poor health as there are fewer side effects.
Multimodal treatment, which is a combination of several treatments, or possibly combined with new treatments, are often recommended for people with any form of mesothelioma. One of the best multimodal approaches to treat mesothelioma is surgery and HIPEC, which is a type of chemotherapy that is used for treating peritoneal mesothelioma.
Clinical Trials for Mesothelioma and Emerging Treatments
Emerging treatments and clinical trials offer a lot of promise, with new therapies such as immunotherapy showing some success in the treatment of mesothelioma. These clinical trials allow doctors to see how effective the new treatment options are, and patients are able to try a new therapy if their cancer is not responding to mainline treatments. Some of the most common experimental therapies are:
- Photodynamic therapy
- Gene therapy
- Mesothelioma virotherapy
- Epigenetic therapy
Palliative Care for Mesothelioma
Mesothelioma treatment is complex options may be limited based on the overall patient health, stage, type of cancer cell and type of cancer. Curative treatment options may not be good options for some patients, so they could be limited to palliative care. Palliative care may be the best choice in these circumstances:
- Poor health of the patient: Patients who are in poor health have a weak immune system, and cannot handle the side effects of chemotherapy, which can damage healthy and cancerous cells.
- Late stage diagnosis: Patients who are diagnosed in the early stages have several treatment options, but those who are diagnosed at stages 3 or 4 have limited options, which is generally palliative care. This is usually the case when cancer has traveled to distant organs and the lymph nodes.
- Aggressive type of cancer or cell type: One of the most aggressive is sarcomatoid mesothelioma and is harder to treat than the epithelioid variety.
If you have been diagnosed with mesothelioma, speaking to a skilled mesothelioma attorney could benefit you financially. You may be able to hold the company or companies responsible that exposed you to asbestos.
- Patients With Mesothelioma See No Survival Benefit With Defactinib Maintenance Therapy. (2019). Retrieved from https://www.curetoday.com/articles/patients-with-mesothelioma-see-no-survival-benefit-with-defactinib-maintenance-therapy-