In April, MesotheliomaHelp reported on the findings of a phase I clinical trial showing that the five-year survival rate for some lung cancer patients treated with Opdivo (nivolumab), an immunotherapy treatment, was “much higher” than historical data. Now, researchers report that results from a phase III clinical trial may help oncologists determine those lung cancer patients, and possibly, mesothelioma patients, who will benefit from the immuno-oncology drug.
Opdivo, developed by Bristol-Myers Squibb, works by blocking the PD-L1 protein and activating the immune system, leading it to attack and kill cancer cells. According to a June 21 press release from The Ohio State University Comprehensive Cancer Center, a team of researchers led by David Carbone, MD, PhD, of The Ohio State University Comprehensive Cancer – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, found that although the trial did not improve progression-free survival when compared with chemotherapy in the overall population, those patients with a high expression of PD-L1 did benefit.
“The good news is that we discovered that a subset of patients who had both high tumor mutation burden and high PDL-1 positive status did experience a significant benefit from immunotherapy,” says Carbone.
Specifically, the researchers report that patients who had “both high tumor mutation burden and high PDL-1 positive status” realized a 75 percent response rate compared to just 16 percent response rate with low mutation burden and low PDL-1. However, the response rates for chemotherapy treatment in these same subsets were nearly the same leading the researchers to conclude that the PDL-1 markers “were selective for immunotherapy.”
Mesothelioma, a rare, asbestos-related cancer of the lining of the lungs, abdomen or heart, is highly aggressive and is resistant to many cancer treatments. The prognosis for mesothelioma patients is usually grim: the average survival time varies from 4 – 18 months after diagnosis. For the close to 3,000 Americans diagnosed with the disease each year, personalized care may bring a breakthrough treatment not previously considered by their physician.
The benefits of personalized care for mesothelioma patients have been proven where researchers have identified genetic biomarkers that reflect the aggressiveness of mesothelioma as well as markers that can assess the effectiveness of a particular treatment.
Opdivo is currently in a phase III clinical trial in the UK for mesothelioma patients. Known as The CheckpOiNt Blockade For Inhibition of Relapsed Mesothelioma, or CONIFRM, the trial has a goal of ‘exploiting the potential of immunotherapy.’
Keytruda, which gained popularity after saving former President Jimmy Carter’s life after sending his melanoma into remission, is also a PD-L1 inhibitor. Both immunotherapy drugs have shown in studies to be effective in fighting pleural mesothelioma. Keytruda is, perhaps, more well known due to eight-year mesothelioma survivor Mavis Nye of England, who went into remission after a two-year clinical trial of the drug.
“This study is an important step toward understanding the impact of tumor mutation burden and PDL-1 in immunotherapy response. This data shows we should evaluate these two factors independently to most accurately define who will benefit from immunotherapy,” says Carbone.
See the full results of the study in the June 22 issue of the New England Journal of Medicine.