Nivolumab in pre-treated malignant pleural mesothelioma: real-world data from the Dutch expanded access program

Our plain-English summary of Nivolumab in pre-treated malignant pleural mesothelioma: real-world data from the Dutch expanded access program, by L. Cantini, R.A. Belderbos, C.J. Gooijer, et al (Translational Lung Cancer Research, 2020).

The study

• Authors: L. Cantini, R.A. Belderbos, C.J. Gooijer, D.W. Dumoulin, R. Cornelissen, S. Baart, J.A. Burgers, P. Baas, J.G.J.V. Aerts
• Journal: Translational Lung Cancer Research
• Published: 2020;9(4):1169-1179
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Randomized phase III trials are ongoing to investigate the efficacy of nivolumab in malignant pleural mesothelioma (MPM), but real-world data are still scarce. In this real-world study, we investigated the clinical outcomes of nivolumab treatment in pre-treated MPM patients.

Methods: Data from 107 nivolumab treated MPM patients within the Dutch expanded access program were retrospectively analyzed. Treatment was independent of programmed death ligand 1 (PD-L1) expression on tumor samples. Univariable and multivariable analyses were performed to evaluate the relationship between clinically important factors, baseline peripheral blood parameters and survival. The landmark method was used to compare the outcome of patients according to their radiological response.

Results: In the full cohort, the median progression-free survival (mPFS) was 2.3 months (95% CI: 1.6-2.9) and the median overall survival (mOS) was 6.7 months (95% CI: 6.2-10.0). After 12 weeks, the disease control rate (DCR) was 37% and the objective response rate (ORR) was 10%. PD-L1 status was determined in 33 patients (30%) and PD-L1 positivity (≥1%) was associated with an improved ORR (36% vs. 9%, P value 0.05), but not with PFS or OS. Low albumin was associated with worse OS (P value 0.002). Median OS was significantly longer for patients who had partial response to treatment (P value 0.0002).

Conclusions: In this real-world analysis, ORR and mOS were lower compared to those obtained in phase II trials. However, exceptional survival rates were observed in patients who had a radiological response. Although we cannot determine whether prognostic or predictive, PD-L1 expression and albumin were associated with greater response rate and may represent useful biomarkers for nivolumab treatment in MPM.

2020 Translational Lung Cancer Research. All rights reserved.

In plain English

This retrospective study reviewed 107 patients with malignant pleural mesothelioma treated at two Dutch hospitals. Their cancer had worsened after at least one course of chemotherapy, and they received the immunotherapy drug nivolumab, 3 mg/kg every 2 weeks, through an expanded access program. Median time without disease progression was 2.3 months (95% confidence interval 1.6 to 2.9), and median overall survival was 6.7 months (95% confidence interval 6.2 to 10.0). At 12 weeks, 37% (40 of 107) had disease control and 10% (11 patients) had a partial response. No deaths were reported among partial responders during a median follow-up of 14.1 months. Only 33 patients were tested for the tumor marker PD-L1. Response was 36% in PD-L1 positive patients versus 9% in PD-L1 negative patients (P value 0.05). Higher blood albumin was associated with lower risk of death. A high monocyte count was associated with shorter time without progression. The authors said that the retrospective design and lack of a control group prevent definitive conclusions on whether PD-L1 and albumin are predictive biomarkers. The article did not report asbestos exposure.

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: retrospective analysis of patients treated in an expanded access program (real-world observational study)
• Who was studied: 107 eligible patients (of 135 treated) with malignant pleural mesothelioma that had progressed after at least one previous line of chemotherapy, treated at Erasmus Medical Center (Rotterdam) and The Netherlands Cancer Institute (Amsterdam); program running since February 2018, data cut-off November 2019
• Exposure: Treatment with nivolumab (a PD-1 inhibitor) at 3 mg/kg intravenously every 2 weeks; asbestos exposure was not studied
• Main results:
  • Full cohort: median progression-free survival 2.3 months (95% CI 1.6 to 2.9); median overall survival 6.7 months (95% CI 6.2 to 10.0)
  • Full cohort at 12 weeks: disease control rate 37% (40 of 107); 11 patients (10%) had an objective radiological response, all partial
  • Full cohort: 6-month overall survival 60% (95% CI 51 to 71%); 1-year overall survival 31% (95% CI 22 to 45%)
  • Partial responders: no deaths reported and only 2 progressed during a median follow-up of 14.1 months
  • Median overall survival was 10.2 months for patients with stable disease and 6.4 months for those with progressive disease; it was not reached for partial responders (log-rank P value 0.0002)
  • Among the 33 patients with PD-L1 testing: objective response rate 36% in PD-L1 positive vs 9% in PD-L1 negative (OR 1.31, 95% CI 1.00 to 1.72, P value 0.05)
  • Stage III/IV patients had shorter progression-free survival than stage I/II patients (median 1.6 vs 3.6 months, HR 1.82, 95% CI 1.11 to 3.01) but similar overall survival
  • Multivariable analysis: high absolute monocyte count was associated with worse progression-free survival (HR 3.16, 95% CI 1.56 to 6.37, P value 0.001)
  • Multivariable analysis: higher albumin was associated with lower risk of death (HR 0.87, 95% CI 0.81 to 0.95, P value 0.002)
  • Median overall survival was 2.5 months for patients with baseline albumin below 38 vs 8.0 months for those above 38
• The authors' conclusion: The authors concluded that PD-L1 expression and albumin were associated with higher response rate. They said the retrospective design and lack of a control group prevent definitive conclusions on their role as potential predictive biomarkers.
• Limitations the authors state:
  • Only 30% of biopsies were stained for PD-L1
  • PD-L1 was often measured on the biopsy taken at diagnosis rather than before nivolumab
  • Safety data were not reported because retrospective data may underreport adverse events
  • No control group, so the predictive role of albumin cannot be determined
  • Too few responders (11) for a multivariable analysis of response

Topics

Medical terms in this study, explained in our Lexicon: Nivolumab (Opdivo), Pleural Mesothelioma, PD-L1, Progression-Free Survival, Median Overall Survival, Biomarker.

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