Now that a new standard of care has been established in frontline mesothelioma, clinical trials are needed to evaluate optimal sequencing with checkpoint inhibitors in the salvage setting and determine whether biomarkers of response to immunotherapy could further tailor treatment to individual patients, said Anne S. Tsao, MD, during a virtual presentation at the 18th Annual Winter Lung Cancer Conference….
Mesothelioma is a complex disease that has a latency period of 20 to 50 years from the time of environmental exposure, with the main causative agent being asbestos, explained Tsao. The primary sites of disease include the pleura, peritoneum, testicle, and pericardium. Additionally, 3 main histologic subtypes can arise, including epithelioid, biphasic, and sarcomatoid.
Historically, mesothelioma was largely chemotherapy resistant, but combinations proved to be more effective, and a current standard of care in the United States is cisplatin plus pemetrexed (Alimta). Then, bevacizumab (Avastin) was added to the combination after demonstrating improved overall survival (OS) compared with cisplatin/pemetrexed alone across all evaluable subpopulations with unresectable malignant pleural mesothelioma in the phase 3 MAPS trial.
“[Chemotherapy plus bevacizumab] is not currently FDA approved, but is commonly used in the United States, as well as various places in Europe and Asia,” explained Tsao, a professor, section chief, and program chair of the Department of Thoracic/Head and Neck Medical Oncology in the Division of Cancer Medicine, as well as the director of the Department of Mesothelioma Program at The University of Texas MD Anderson Cancer Center.
In 2020, a new standard of care was introduced to the frontline setting with the findings of the phase 3 CheckMate-743 trial. The study showed an improvement in OS and progression-free survival (PFS) with the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) versus cisplatin or carboplatin plus pemetrexed in patients with unresectable pleural mesothelioma.
At a median follow up of 29.7 months, the median OS was 18.1 months with nivolumab/ipilimumab versus 14.1 months with chemotherapy (HR, 0.74; 95% CI, 0.60-0.91; P = .002). The 2-year OS rates were 41% and 27%, respectively, and the 2-year PFS rates were 16% and 7%, respectively.
The OS and PFS was improved with the immunotherapy combination, irrespective of disease histology; however, patients with non-epithelioid mesothelioma (25% of the total population) derived a greater OS benefit (HR, 0.47; 95% CI, 0.35-0.63) compared with the epithelioid subgroup (HR, 0.93; 95% CI, 0.68-1.28).
“If a patient has biphasic or sarcomatoid [disease], we need to consider giving them ipilimumab and nivolumab in the frontline setting,” said Tsao. “The magnitude of benefit from CheckMate-743 was significant, and we do see remarkable responses with high duration of response [with the immunotherapy combination].”
When broken down by PD-L1 expression status, which patients were not stratified for, patients with PD-L1 expression of 1% or greater appeared to derive more benefit from nivolumab/ipilimumab versus patients with a PD-L1 expression of less than 1%.
“We do need additional investigation into predictive biomarkers for immunotherapy. As of right now, we do not use biomarkers in mesothelioma to predict whether or not somebody should be receiving immunotherapy,” added Tsao.
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