1896MO - Volumetric PET response assessment outperforms conventional criteria in patients receiving high-dose pembrolizumab for malignant mesothelioma

Background

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 2^nd-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 retrospectively analyzed. RECIST v1.1, mRECIST, PERCIST_SULpeak and PERCIST_MTV 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. Programmed Cell Death Protein 1 (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 rates were 7%, 7%, 30%, and 30% based on RECIST v1.1, mRECIST, PERCIST_SULpeak, and PERCIST_MTV response criteria, respectively. Response according to PERCIST_MTV predicted prolonged OS or PFS (p < 0.01), whereas all other imaging criteria and PD-L1 expression did not.

Conclusions

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

PD Dr. med. Daniel C. Christoph.

Funding

Has not received any funding.

Disclosure

D.C.C. Christoph: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Chugai; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck, Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda. W.P. Fendler: Advisory/Consultancy: BTG; Advisory/Consultancy: Endocyte; Advisory/Consultancy: Ipsen; Honoraria (self): RadioMedix. L. Kessler: Honoraria (self): Sanofi. M. Metzenmacher: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck, Sharp & Dohme; Honoraria (self): Roche; Honoraria (self): Takeda. T. Hager: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Chugai; Honoraria (self): Merck, Sharp & Dohme; Honoraria (self): Roche. K. Herrmann: Non-remunerated activity/ies: ABX; Honoraria (self): Adacap; Honoraria (self): Amgen; Honoraria (self): Bayer; Honoraria (self), Research grant/Funding (institution): BTG; Honoraria (self): Curium; Honoraria (self): Endocyte; Honoraria (self): GE Healthcare; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): Siemens Healthineers; Honoraria (self): Sirtex, Honoraria (self), Non-remunerated activity/ies: Sofie Biosciences; Honoraria (self): ymabs. All other authors have declared no conflicts of interest.