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Mesothelioma Patients Stand to Gain from Serum Biomarker That May Predict Response to Immunotherapy Drugs


MesotheliomaHelp reported in December that researchers from the UK reported a blood test may be useful for identifying “how well and how long a patient might respond to chemotherapy.” Now, researchers report a serum biomarker could do the same thing for patients treated with certain checkpoint inhibitors.

Researchers from the Dana Farber Cancer Institute report that in melanoma patients receiving immune checkpoint therapy targeting the CTLA-4 and PD-1 proteins the levels of the ANGPT2 serum biomarker either increased or decreased depending on the efficacy of the treatment, according to a Dec. 21 press release from the American Association of Cancer Research.

“In this study, we found ANGPT2 to be a predictive and prognostic biomarker of response to the inhibitors of immune checkpoints CTLA-4 and PD-1,” said F. Stephen Hodi, MD, director of the Melanoma Center at Dana-Farber Cancer Institute, professor of medicine and investigator at the Ludwig Center at Harvard Medical School in Boston.

Dr. Hodi said that due to the “complexity of the biology of cancer” finding a serum biomarker that can be predictive is “a huge challenge.” His team set out to determine the role the formation of new blood vessels from ANGPT2 played in immune regulation and to see if ANGPT2 could be a potential biomarker with immune checkpoint inhibitors.

The team looked at results of three cohorts of over 40 patients each treated with ipilimumab (Yervoy), ipilimumab plus bevacizumab (Avastin), and an anti-PD1 nivolumab (Opdivo), or pembrolizumab (Keytruda). They found that of the 134 patients those who started with high levels of ANGPT2 and had the largest fold changes, change from the initial value of ANGPT2 to the final value of the biomarker, had the worst survival. On the other hand, those with low pretreatment protein levels and small fold changes had the best survival.

Mesothelioma and melanoma are both notoriously aggressive and difficult to treat, and both have shown some success with both ipilimumab (Yervoy), a CTLA-4 checkpoint inhibitor from Bristol-Myers Squibb, and Keytruda, an immunotherapy drug from Merck that works by targeting the cellular pathway PD-1/PD-L1. Mavis Nye of England, who has had pleural mesothelioma for seven years, was brought to remission through a clinical trial with Keytruda.

“This correlation between the dynamic ANGPT2 levels and survival consolidates the role of this protein as a prognostic biomarker,” the team concluded.

When oncologists can quickly determine whether the immunotherapy is working they can adjust treatments as appropriate to ensure the patient is receiving the most effective care. Research to find a biomarker that can be used to monitor this is critical for improving survival in cancer patients.

Nearly 3,000 Americans are diagnosed with mesothelioma, an asbestos-caused cancer, each year. There is no cure for the cancer.

Read the full study in the Dec. 21 issue of Cancer Immunology Research.

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