RT Journal Article
SR Electronic
T1 Volumetric PET response assessment outperforms conventional criteria in patients receiving high-dose pembrolizumab for malignant mesothelioma
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP jnumed.120.245803
DO 10.2967/jnumed.120.245803
A1 Ferdinandus, Justin
A1 Barbato, Francesco
A1 Chodyla, Michal
A1 Fendler, Wolfgang Peter
A1 Kessler, Lukas
A1 Pomykala, Kelsey L.
A1 Metzenmacher, Martin
A1 Krefting, Frederik
A1 Hager, Thomas
A1 Umutlu, Lale
A1 Herrmann, Ken
A1 Christoph, Daniel Christian
YR 2020
UL http://jnm.snmjournals.org/content/early/2020/06/12/jnumed.120.245803.abstract
AB 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.