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. 2020 Aug;9(4):1169-1179.
doi: 10.21037/tlcr-19-686.

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

Luca Cantini  1   2   3 , Robert A Belderbos  1   2 , Cornedine J Gooijer  4 , Daphne W Dumoulin  1   2 , Robin Cornelissen  1   2 , Sara Baart  1   2   5 , Jacobus A Burgers  4 , Paul Baas  4 , Joachim G J V Aerts  1   2
Affiliations

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

Luca Cantini et al. Transl Lung Cancer Res. 2020 Aug.

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.

Keywords: Checkpoint inhibitors; PD-L1; immunotherapy; malignant pleural mesothelioma (MPM); nivolumab.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-19-686). DWD reports personal fees from Roche, BMS, MSD, Pfizer, Astra Zeneca and Novartis outside the submitted work. RC reports speakers fee from Roche, Pfizer and BMS, personal fees from Advisory Board MSD and Advisory Board Roche outside the submitted work. JAB reports other from Bristol-Meyers Squibb, MSD B.V., F. Hoffmann- La Roche Ltd. during the conduct of the study. PB reports other from Bristol-Myers Squibb, MSD B.V., AstraZeneca, Takeda outside the submitted work. JGJVA reports personal fees and non-financial support from MSD, personal fees from BMS, Boehringer Ingelheim, Amphera, Eli-Lilly, Takeda, Bayer, Roche, Astra Zeneca outside the submitted work; in addition, JGJVA has a patent allogenic tumor cell lysate licensed to Amphera, a patent combination immunotherapy in cancer pending, and a patent biomarker for immunotherapy pending; JGJVA serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. The other authors have no conflicts of interest to declare. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Kaplan-Meier curves of survival in the entire cohort of nivolumab treated MPM patients (median follow-up time of 10.1 months). (A) Progression-free survival in the entire cohort; (B) overall survival in the entire cohort. PFS, progression-free survival; OS, overall survival.
Figure 2
Figure 2
Kaplan-Meier curves of survival of subgroups based on stage of disease, histological subtype and programmed death ligand 1 (PD-L1) status. (A) Progression-free survival and (B) overall survival by stage of disease as determined by IASLC 8th edition of TNM for pleural mesothelioma. (C) Progression-free survival and (D) overall survival by histology. (E) Progression-free survival and (F) overall survival in patients with a PD-L1 expression ≥1% versus in those with a PD-L1 expression <1%. PFS, progression-free survival; OS, overall survival; PD-L1, programmed death ligand 1.
Figure 3
Figure 3
Kaplan-Meier curves of survival according to best overall radiological response. (A) Progression-free survival in patients with a partial response and stable disease as objective response to nivolumab treatment; (B) overall survival in patients with a partial response, stable disease and progressive disease as objective response to nivolumab treatment. PFS, progression-free survival; OS, overall survival; PR, partial response; SD, stable disease; PD, progressive disease.
Figure 4
Figure 4
Expression of programmed death ligand 1 (PD-L1) according to objective response to nivolumab treatment. PR, partial response; SD, stable disease; PD, progressive disease; PD-L1, programmed death ligand 1.
Figure 5
Figure 5
Kaplan-Meier curves of survival in patient groups per quartile of albumin level. OS, overall survival.
Figure S1
Figure S1
Flow diagram of study population. PD-L1, programmed death ligand 1.
See this image and copyright information in PMC

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