Volumetric PET response assessment outperforms conventional criteria in patients receiving high-dose pembrolizumab for malignant mesothelioma.

Introduction: Fixed-dose pembrolizumab (200 mg abs., d1, q3w) for the treatment of malignant pleural mesothelioma did not result in survival benefit in the phase 3 PROMISE-meso trial compared to 2nd-line chemotherapy. Due to lack of validated imaging response criteria, responder-subgroups with potential survival benefit have not yet been identified. Here, we administered high-dose pembrolizumab (10 mg/kg, d1, q2w) considering the KEYNOTE-028 trial and assessed the prognostic value of PET metabolic response in patients with chemotherapy-resistant malignant mesothelioma of the pleura or peritoneum. Methods: Data from 27 patients with baseline and follow-up 18F-FDG PET/CT imaging were analyzed. RECIST v1.1, mRECIST, PERCISTSULpeak and PERCISTMTV were used separately to categorize responders in CT and PET imaging studies. Progression-free survival (PFS) and overall survival (OS) of responders were compared to non-responders using Kaplan-Meier and log-rank analyses. PD-L1 expression status was assessed and its association with outcome was investigated. Results: 27 patients had 18F-FDG-PET/CT imaging at baseline and after at least 4 cycles pembrolizumab. Median PFS and OS were 3.4 and 15.1 months, respectively. Response rate (RR) was 7%, 7%, 30%, and 30% based on RECIST v1.1, mRECIST, PERCISTSULpeak, and PERCISTMTV response criteria, respectively. Response according to PERCISTMTV predicted prolonged OS or PFS (P < 0.01), whereas all other imaging criteria and PD-L1 expression did not. Conclusion:18F-FDG PET metabolic volume response predicts survival in patients with malignant mesothelioma receiving high-dose pembrolizumab. These results should prompt inclusion of PET response assessment in future phase 3 clinical trials and investigation of high-dose pembrolizumab instead of fixed-dose.