NEW YORK – Newly identified biomarkers in mesothelioma patients' exhaled breath may be useful in predicting if they're likely to respond to treatment, researchers reported over the weekend at the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer.
Kevin Lamote, an assistant professor at the University of Antwerp who presented the research at the WCLC taking place in Singapore, said in a webcast press briefing that volatile organic compounds (VOCs) can be detected as biomarkers in patients' breath. The VOCs reflect changes in patients' metabolism as they're developing mesothelioma after asbestos exposure, Lamote noted.
"By inhaling asbestos, you induce necrosis and induce oxidative stress, and this liberates these oxidative volatile compounds, and we can detect them in the exhaled breath," he said.
His team hopes the breath analysis could provide a new way to select treatment and monitor response, compared to more invasive methods like blood draws or biopsies. Most mesothelioma patients typically receive chemotherapy, he said, but new treatments are emerging. In 2020, the US Food and Drug Administration approved Bristol Myers Squibb's immunotherapy combination Opdivo (nivolumab) and Yervoy (ipilimumab) as a first-line treatment for an all-comer population of patients with unresectable malignant pleural mesothelioma.
Lamote noted that the Opdivo-Yervoy combination benefited these patients, but there is room for improvement. The CheckMate-743 study that led to the FDA approval demonstrated a response rate of 40 percent versus 43 percent in the chemo arm. The Opdivo-Yervoy combination did improve overall survival in that study, with a median survival of 18.1 months on Opdivo-Yervoy compared to 14.1 months on chemo.
"There's a lack [of biomarkers] to select these patients who will respond to certain treatments," Lamote said. "In order to improve the survival rate, we tried to identify companion diagnostic biomarkers in exhaled breath."
Prior studies from Lamote's group have explored using exhaled breath VOCs to diagnose malignant pleural mesothelioma, finding that their VOC model had a high negative predictive value and could help rule out cancer for patients who had other asbestos-related diseases.
Other researchers have also explored breath-based biomarkers in mesothelioma, including one study that used eNose technology, a device that can analyze compounds in gas samples, to find differences in breath profiles between responders and nonresponders to Opdivo and Yervoy.
The latest study presented at the WCLC included 15 patients with malignant pleural mesothelioma who were treated with either chemotherapy, an immunotherapy combination, or dendritic cell vaccination. The researchers collected exhaled breath samples prior to treatment and every three months since beginning treatment to determine if the VOCs differed between responders and nonresponders.
Lamote's team used multi-capillary column-ion mobility spectrometry to characterize VOCs in these patients' breath and in the surrounding air to correct for potential confounding factors.
The researchers first examined the post-treatment samples including 10 samples from patients with stable disease and nine samples for patients with progressive disease. In this analysis, they identified six VOCs that appeared to differentiate between responders and nonresponders, Lamote said.
Then, researchers applied the model with these six VOCs to the pretreatment exhaled breath samples. The model could predict which patients would be responders and nonresponders with 100 percent sensitivity, 87.5 percent specificity, and 93.8 percent accuracy.
Lamote said his team aims to validate this preliminary research and the six-VOC predictive model in a larger cohort. They also hope to be able to identify the VOCs using gas chromatography mass spectrometry in future studies and link them to underlying metabolites.
"We also will define a VOC-profile for each treatment," he said, noting that because most patients in the present study got chemotherapy, it was not powered to differentiate responses between those who got chemotherapy and the patients on immunotherapy.