Volumetric PET Response Assessment Outperforms Conventional Criteria in Patients Receiving High-Dose Pembrolizumab for Malignant Mesothelioma

Our plain-English summary of Volumetric PET Response Assessment Outperforms Conventional Criteria in Patients Receiving High-Dose Pembrolizumab for Malignant Mesothelioma, by J. Ferdinandus, F. Barbato, M. Chodyla, et al (Journal of Nuclear Medicine, 2021).

The study

• Authors: J. Ferdinandus, F. Barbato, M. Chodyla, W.P. Fendler, L. Kessler, K.L. Pomykala, M. Metzenmacher, F. Krefting, T. Hager, L. Umutlu, K. Herrmann, D.C. Christoph
• Journal: Journal of Nuclear Medicine
• Published: 2021;62(2):191-194
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Fixed-dose pembrolizumab (200 mg absolute, day 1, every 3 wk) for the treatment of malignant pleural mesothelioma did not result in survival benefit in the phase 3 PROMISE-meso trial compared with second-line chemotherapy. Because of 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, day 1, every 2 wk) 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, version 1.1; modified RECIST; and PERCIST using both tumor lesion metabolic activity in a 1 cm3 spheric region of interest of up to 5 target lesions (PERCISTSULpeak) and metabolic tumor volume PERCIST (PERCISTMTV) were applied separately to categorize responders in CT and PET imaging studies. Progression-free survival (PFS) and overall survival (OS) were compared between responders and nonresponders using Kaplan-Meier and log-rank analyses. Programmed cell death protein 1 ligand expression status was assessed, and its association with outcome was investigated. Results: Twenty-seven 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 mo, respectively. Response rates were 7%, 7%, 30%, and 30% based on RECIST, modified RECIST, PERCISTSULpeak, and PERCISTMTV response criteria, respectively. Response according to PERCISTMTV predicted prolonged OS or PFS (P < 0.01), whereas all other imaging criteria and programmed cell death protein 1 ligand 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.

© 2021 by the Society of Nuclear Medicine and Molecular Imaging.

In plain English

This single-arm retrospective study from University Hospital Essen, Germany, looked at patients with malignant mesothelioma of the pleura or peritoneum. Their disease had progressed after chemotherapy, and they received high-dose pembrolizumab, an immunotherapy drug, off-label between June 2015 and December 2017. Asbestos exposure was not reported. Of 52 eligible patients, 27 had PET/CT scans before treatment and at follow-up and were analysed. The authors compared two CT-based and two PET-based ways of judging whether tumors responded. Median overall survival was 15.1 months and median progression-free survival 3.4 months. Response rates were 7.4% by each CT method and 29.6% by each PET method. Only response measured by PET metabolic tumor volume was associated with longer survival. For responders versus non-responders, median progression-free survival was 13.5 versus 1.7 months and overall survival 24.5 versus 9.2 months (both P less than 0.01). Tumor PD-L1 levels showed no significant link to survival. The authors concluded that metabolic volume response predicts survival in this setting, but said their sample was too small for definitive conclusions.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-arm retrospective study
• Who was studied: 27 patients with chemotherapy-pretreated malignant mesothelioma of the pleura and/or peritoneum, treated at University Hospital Essen, Germany. They were selected from 52 eligible patients and had PET/CT at baseline and after four cycles (one patient after five). There were 23 men and 4 women, with a median age at diagnosis of 68 (range 51-82). Treatment ran from June 2015 to December 2017, with follow-up to December 2019.
• Exposure: The exposure studied was a treatment, not asbestos: high-dose pembrolizumab (10 mg/kg, day 1, every 2 weeks), given off-label for up to two years after progression on at least one line of platinum- and pemetrexed-based chemotherapy. The article does not report asbestos or fiber exposure.
• Main results:
  • In the 27 analysed patients, median follow-up was 29.7 months. Median overall survival was 15.1 months and median progression-free survival 3.4 months.
  • Objective response rates were 7.4% (RECIST v1.1), 7.4% (mRECIST), 29.6% (PERCIST SULpeak) and 29.6% (PERCIST metabolic tumor volume). In the table, each 29.6% is 8 of 27 patients.
  • Only response by PERCIST metabolic tumor volume was associated with longer progression-free and overall survival. The medians were 1.7 vs. 13.5 months for progression-free survival and 9.2 vs. 24.5 months for overall survival, both P less than 0.01. The article states that responders had the longer survival.
  • RECIST and mRECIST agreed in 23 of 27 patients. The two PET-based criteria agreed in 14 of 27 patients.
  • PD-L1 expression was available for 26 of 27 patients. It was not associated with response by any imaging criteria. There was no significant difference in overall or progression-free survival between patients whose tumors did or did not express PD-L1.
  • The authors reported that high-dose pembrolizumab was well tolerated.
• The authors' conclusion: The authors concluded that PERCIST-derived metabolic volume response predicts survival in pre-treated patients with malignant mesothelioma receiving high-dose pembrolizumab, and that no other imaging criteria predicted survival. They said the results warrant including PET response assessment in future clinical trials and routine practice.
• Limitations the authors state:
  • The sample size does not allow definitive conclusions on whether PET, or metabolic tumor volume response specifically, can guide treatment decisions.
  • Patients with pleural and/or peritoneal mesothelioma were combined. The authors note that peritoneal disease has a much poorer prognosis.
  • Patients who died before the first follow-up PET/CT could not be included in the efficacy analysis.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pembrolizumab (Keytruda), Malignant Mesothelioma, Pleural Mesothelioma, Chemotherapy, Pleura, Peritoneum, Modified RECIST (mRECIST), Progression-Free Survival.

Related studies

• Efficacy and safety of pembrolizumab in patients with advanced mesothelioma in the open-label, single-arm, phase 2 KEYNOTE-158 study — T.A. Yap, K. Nakagawa, et al. (2021)
• Prospective real-world study on the pharmacokinetics of pembrolizumab in patients with solid tumors — D.P. Hurkmans, S.D.T. Sassen, et al. (2021)
• Impressive clinical response to anti-PD-1 therapy in epithelioid mesothelioma with high clonal PD-L1 expression and EML4-ALK rearrangement — G. Bronte, A. Delmonte, et al. (2020)
• Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study — A. Marabelle, M. Fakih, et al. (2020)
• Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial — E.W. Alley, J. Lopez, et al. (2017)
• Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1-2 trial — B. Geoerger, H.J. Kang, et al. (2020)

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