ESMO Open

Our medical research library holds 10 studies published in ESMO Open (2017–2025). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 10 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Elsevier
• Published: 2016 to the present, England
• Language: English
• ISSN: 2059-7029 (electronic)
• Its record in the NLM Catalog

2020s

• Comprehensive genomic and transcriptomic analysis enables molecularly guided therapy options in peritoneal and pleural mesothelioma. L. Möhrmann, M. Werner, M. Oleś, et al. 2025;10(4):104532. PubMed · Publisher · Free full text

  Abstract

  Introduction: Peritoneal, pericardial and pleural mesothelioma (PeM/PcM/PM) are rare and aggressive diseases with limited survival. Molecularly guided therapy is currently not part of standard care.

  Methods: This study integrates molecular and clinical data from 51 patients (among them 28 PM, one PcM, 21 PeM and one synchronous PeM/PM) enrolled in the National Center for Tumor Diseases and the German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER), a multicenter precision oncology registry trial addressing adults with rare advanced-stage cancers. Analysis comprised both somatic and germline whole exome sequencing/whole genome sequencing and transcriptome analysis leading to personalized treatment recommendations issued by a dedicated molecular tumor board. To assess clinical efficacy, progression-free survival (PFS) ratios comparing molecularly informed therapies (PFS2) to preceding systemic therapies (PFS1) were calculated. Efficacy of immune checkpoint inhibition applied during the observation period was assessed accordingly.

  Results: Cancer-related genes altered in more than 5 out of 44 assessable patients were BAP1, CDKN2A, NF2, SETD2 and TP53. Somatic (n = 23) or germline (n = 9) alterations in homologous recombination-related genes were detected in 27/44 patients. In 21/44 cases, they were supported by positive combined homologous recombination deficiency scores or BRCAness signature. Following American College of Medical Genetics and Genomics guidelines, (likely) pathogenic germline variants in autosomal dominant cancer predisposition genes were found in 8/51 patients. Molecular tumor board recommendations were issued in 46 cases and applied in 6 cases. Mean PFS ratio was 2.45 (n = 5). Median PFS2 was 6.5 months (n = 6), median PFS1 was 4.0 months (n = 5). A total of 27 patients received immune checkpoint inhibition during the observation period leading to a mean PFS ratio of 1.69 (n = 19).

  Conclusions: In mesothelioma, comprehensive molecular analysis can provide valuable clinically actionable information. Molecularly informed therapy recommendations can lead to clinical benefit.

  Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.

• First-in-human study of a thorium-227-labeled mesothelin-targeting antibody-chelator conjugate (MSLN-TTC), in patients with malignant mesothelioma and other solid tumors. A. Minchom, O. Lindén, D.G. Knapen, et al. 2025;10(12):105905. PubMed · Publisher · Free full text

  Abstract

  Introduction: BAY 2287411 [227Th-anetumab corixetan; mesothelin-targeting antibody-chelator conjugate (MSLN-TTC)] is a targeted alpha therapy consisting of a fully human mesothelin-targeting monoclonal antibody conjugated with a 3,2-hydroxypyridinone (3,2-HOPO) chelator radiolabeled with the alpha particle-emitting radionuclide thorium-227. This phase I study determined the safety, pharmacokinetics, and antitumor activity of MSLN-TTC in mesothelin-expressing mesothelioma and serous ovarian cancer.

  Methods: MSLN-TTC was administered i.v. 1.5, 2.5, or 3.5 MBq of thorium-227 and with a total antibody dose of 10, 30, 50, or 150 mg every 6 weeks to 36 patients included in the intention-to-treat population. Adverse events, tumor response according to RECIST 1.1 and mRECIST criteria, and progression-free survival were determined. Tumor mesothelin expression was assessed retrospectively.

  Results: In dose escalation, 35 patients (30 with malignant pleural mesothelioma) received MSLN-TTC across three thorium-227 dose levels and four total antibody doses. No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached due to treatment discontinuations following 45.7% of the patients developing neutralizing antibodies. The most common treatment-emergent adverse events of any grade were fatigue (10/36, 27.8%), decreased lymphocyte count (7/36, 19.4%), nausea (7/36, 19.4%), anemia (6/36, 16.7%), and infusion-related reaction (6/36, 16.7%). The disease control rate was 34.3%, including 12 stable diseases (12/36, 34.3%). No complete or partial responses were observed. The median progression-free survival was 70 days (95% confidence interval 29-161 days).

  Conclusions: MSLN-TTC showed good tolerability, but the maximum tolerated dose could not be determined due to discontinuations after antidrug antibody formation. Stable disease was observed in 12 out of 36 patients.

  Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.

• Follow-up after first-Line nivOlumab plus ipilimumab in patients with diffuse pleuRal mesotheliomA: a real-world Dutch cohort study-FLORA. L.H. Douma, M.M. Hofman, F. Zwierenga, et al. 2025;10(2):104123. PubMed · Publisher · Free full text

  Abstract

  Background: Diffuse pleural mesothelioma (dPM) is an aggressive malignancy, primarily treated with palliative systemic therapy. Since 2022, nivolumab-ipilimumab (nivo/ipi) has replaced chemotherapy as the standard first-line treatment for dPM in the Netherlands. Chemotherapy remains a rational second-line treatment. The real-world effectiveness of second-line treatment after doublet immunotherapy remains unknown. The FLORA study aimed to provide an overview of treatment patterns in patients with dPM after first-line nivo/ipi and evaluate the effectiveness of second-line chemotherapy based on real-world data.

  Patients And Methods: FLORA was a Dutch multicenter retrospective cohort study. Clinical data were collected from the medical records. The primary endpoints were treatment patterns after nivo/ipi and median overall survival (mOS) of patients receiving second-line chemotherapy. The secondary endpoints were objective response rate (ORR), median progression-free survival (mPFS) of second-line chemotherapy, and subgroup analyses (Eastern Cooperative Oncology Group performance status and histological subtype). The study also updated the mOS for first-line nivo/ipi patients.

  Results: Between May 2021 and July 2023, 277 patients with dPM receiving first-line nivo/ipi therapy were included. Sixty-eight percent of the patients were male, with a median age of 72 years (interquartile range 67-77 years). The histological subtypes were epithelioid (62%), sarcomatoid (22%), biphasic (13%), and unknown (3%). One hundred and two (47%) of the 218 patients with disease progression received second-line treatment, of whom 83 received second-line platinum-pemetrexed chemotherapy. The mOS and mPFS for second-line chemotherapy were 8.2 months ([95% confidence interval (CI) 7.4-9.1 months] and 5.6 months (95% CI 4.9-6.3 months), respectively, with an ORR of 37%. Poor performance score was the main reason for not receiving second-line treatment.

  Conclusion: This study provides the first real-world data on subsequent treatment of patients with dPM with disease progression on nivo/ipi, resulting in an mOS of 8.2 months after second-line chemotherapy.

  Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

• Update on gene fusions and the emerging clinicopathological landscape of peritoneal and pleural mesotheliomas and other neoplasms. N. Benzerdjeb, P. Dartigues, V. Kepenekian, et al. 2024;9(8):103644. PubMed · Publisher · Free full text

  Abstract

  Background: Mesothelioma is a rare and aggressive malignant neoplasm arising from mesothelial cells, which occasionally manifests recurrent fusions. EWSR1/FUS-CREB, YY1, MAP3K8, NR4A3, and ALK-rearranged proliferations have been reported in limited series with no clear histological or clinical correlations, limiting clinicians' ability to assess prognosis and integrate these new entities into therapeutic decisions. The aim of this study was to better characterize these rearranged proliferations histologically, molecularly, and clinically.

  Methods: Clinical, pathological, and comprehensive transcriptome and mutation data were collected for each case.

  Results: A total of 41 tumors were included, encompassing 7 ALK, 10 MAP3K8, 4 NR4A3, 8 ESWR1/FUS::ATF1, 8 EWSR1::YY1, and 4 SUFU-fused cases. We found a female predominance, except for cases harboring NR4A3 and SUFU; and most patients were around 60 years of age, but those harboring ALK or EWSR1/FUS::ATF1 gene fusions were younger. Each group exhibited distinct histological, immunohistochemical, molecular features, and oncological courses. Specifically, MAP3K8 and ALK presented PAX8+ papillary proliferations, ESWR1/FUS::ATF1 and EWSR1::YY1 displayed angiomatoid fibrous histiocytoma-like patterns, while SUFU showcased 'tissue culture'-like spindle cell proliferation. Poor prognosis factors were the pleural site, male sex, Ki67 ≥10%, and ESWR1/FUS::ATF1 or SUFU gene fusions.

  Conclusions: This study significantly broadens the spectrum of mesothelial tumors associated with fusions, offering insight into novel epithelioid (mesothelial) proliferations with distinctive histological appearances, molecular profiles, and prognoses to guide adapted treatments for patients.

  Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

• Molecular alterations and potential actionable mutations in peritoneal mesothelioma: a scoping review of high-throughput sequencing studies. M.V. Dietz, J.P. van Kooten, M.S. Paats, et al. 2023;8(4):101600. PubMed · Publisher · Free full text

  Abstract

  Background: Peritoneal mesothelioma (PeM) is a rare malignancy with a poor prognosis. Currently there is a lack of effective systemic therapies. Due to the rarity of PeM, it is challenging to study new treatment options. Off-label use of targeted drugs could be an effective approach. This scoping review aims to explore the genomic landscape of PeM to identify potential therapeutic targets.

  Materials And Methods: A systematic literature search of Embase, Medline, Web of Science, the Cochrane Library, and Google Scholar was carried out up to 1 November 2022. Studies that reported on molecular alterations in PeM detected by high-throughput sequencing techniques were included. Genes that were altered in ≥1% of PeMs were selected for the identification of potential targeted therapies.

  Results: Thirteen articles were included, comprising 824 PeM patients. In total, 142 genes were altered in ≥1% of patients, of which 7 genes were altered in ≥10%. BAP1 was the most commonly altered gene (50%). Other commonly altered genes were NF2 (25%), CDKN2A (23%), CDKN2B (17%), PBRM1 (15%), TP53 (14%), and SETD2 (13%). In total, 17% of PeM patients were carriers of a germline mutation, mainly in BAP1 (7%).

  Conclusions: This scoping review provides an overview of the mutational landscape of PeM. Germline mutations might be a larger contributor to the incidence of PeM than previously thought. Currently available targeted therapy options are limited, but several targeted agents [such as poly (ADP-ribose) polymerase (PARP), enhancer of zeste homolog 2 (EZH2), and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors] were identified that might provide new targeted therapy options in the future.

  Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

• Final results of DIADEM, a phase II study to investigate the efficacy and safety of durvalumab in advanced pretreated malignant pleural mesothelioma. S. Canova, G.L. Ceresoli, F. Grosso, et al. 2022;7(6):100644. PubMed · Publisher · Free full text

  Abstract

  Background: Malignant pleural mesothelioma (MPM) is a cancer with a high mortality rate and few therapeutic options. After platinum-pemetrexed combination, no further promising drug seems to be effective. Immune checkpoint inhibitors may have some activity in pretreated patients and no data are available in this population about durvalumab.

  Materials And Methods: DIADEM was a multicenter, open-label, single-arm, phase II trial aimed at evaluating the efficacy and safety of durvalumab. Patients with locally advanced/metastatic MPM who progressed after platinum-pemetrexed chemotherapy were enrolled to receive durvalumab (1500 mg, intravenously Q4W) for 12 months or until evidence of disease progression or unacceptable toxicity. The primary endpoint was the proportion of patients alive and free from progression at 16 weeks (PFS16wks) calculated from treatment initiation. Secondary endpoints were progression-free survival, overall survival, overall response rate, and safety.

  Results: Sixty-nine patients with a median age of 69 years (range 44-82 years) were enrolled; 62 patients (89.9%) had epithelioid histotype. As first-line treatment, all patients received platinum derivatives-pemetrexed combination (60.9% with carboplatin and 39.1% with cisplatin). As of March 2021, the median follow-up was 9.2 months (interquartile range 5.2-11.1 months). Six patients (8.7%) completed the 12-month treatment; 60 patients discontinued, of whom 42 for progressive disease, and 4 died. Seventeen patients (28.3%; 95% confidence interval 17.5% to 41.4%) were alive or free from progression at 16 weeks. Eleven patients (18.6%) had a grade 3 or 4 treatment-related adverse event (AE), and one (1.4%) had a grade ≥3 immune-related, treatment-related AE. There was one drug-related death.

  Conclusion: Durvalumab alone in pretreated non-selected MPM did not reach a meaningful clinical activity, showing any new major safety issue signals.

  Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

• Long-term benefit of lurbinectedin as palliative chemotherapy in progressive malignant pleural mesothelioma (MPM): final efficacy and translational data of the SAKK 17/16 study. M. Mark, S. Rusakiewicz, M. Früh, et al. 2022;7(3):100446. PubMed · Publisher · Free full text

  Abstract

  Background: The SAKK 17/16 study showed promising efficacy data with lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma. Here, we evaluated long-term outcome and analyzed the impact of lurbinectedin monotherapy on the tumor microenvironment at the cellular and molecular level to predict outcomes.

  Material And Methods: Forty-two patients were treated with lurbinectedin in this single-arm study. Twenty-nine samples were available at baseline, and seven additional matched samples at day one of cycle two of treatment. Survival curves and rates between groups were compared using the log-rank test and Kaplan-Meier method. Statistical significance was set at P value <0.05.

  Results: Updated median overall survival (OS) was slightly increased to 11.5 months [95% confidence interval (CI) 8.8-13.8 months]. Thirty-six patients (85%) had died. The OS rate at 12 and 18 months was 47% (95% CI 32.1% to 61.6%) and 31% (95% CI 17.8% to 45.0%), respectively. Median progression-free survival was 4.1 months (95% CI 2.6-5.5 months). No new safety signals were observed. Patients with lower frequencies of regulatory T cells, as well as lower tumor-associated macrophages (TAMs) at baseline, had a better OS. Comparing matched biopsies, a decrease of M2 macrophages was observed in five out of seven patients after exposure to lurbinectedin, and two out of four patients showed increased CD8+ T-cell infiltrates in tumor.

  Discussion: Lurbinectedin continues to be active in patients with progressing malignant pleural mesothelioma. According to our very small sample size, we hypothesize that baseline TAMs and regulatory T cells are associated with survival. Lurbinectedin seems to inhibit conversion of TAMs to M2 phenotype in humans.

  Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

• The clinical utility of comprehensive measurement of autoimmune disease-related antibodies in patients with advanced solid tumors receiving immune checkpoint inhibitors: a retrospective study. N. Izawa, H. Shiokawa, R. Onuki, et al. 2022;7(2):100415. PubMed · Publisher · Free full text

  Abstract

  Background: The comprehensive measurement of autoimmune disease-related antibodies (Abs) before immune checkpoint inhibitor (ICI) treatment may be useful for predicting the development of immune-related adverse events (irAEs); however, the clinical utility is not well known.

  Materials And Methods: We retrospectively analyzed patients with advanced solid tumors treated with ICI monotherapy or doublet combination therapy between July 2014 and December 2020 at single institute. Anti-nuclear antibody (ANA), anti-thyroglobulin (Tg) Ab, anti-thyroid peroxidase (TPO) Ab, anti-glutamic acid decarboxylase (GAD) Ab, anti-acetylcholine esterase receptor (AchR) Ab, and platelet-associated immunoglobulin G (PA-IgG) Ab were comprehensively measured for the screening before ICI therapy.

  Results: Of 275 registered patients (median age, 70 years; male, 64.4%; Eastern Cooperative Oncology Group performance status of 0 or 1, 88.7%; and prior regimen of 0-1/≥2, 88.7%/11.3%), 128 non-small-cell lung cancer, 35 gastric cancer, 33 head and neck cancer, 24 melanoma, 19 renal cell carcinoma, 13 urothelial carcinoma, 12 esophageal cancer, 5 malignant mesothelioma of pleura, 2 endometrial cancer, and 4 other cancer were included. The number of patients with positive ANA, Tg, TPO, PA-IgG, GAD, and AchR Abs was 52 (24.9%), 38 (14.5%), 11 (10.1%), 6 (3.5%), 5 (2.0%), and 1 (0.5%), respectively. There was no association between the development of any irAEs and Abs positivity, while thyroid dysfunction developed more frequently among patients with than without Tg Ab or TPO Ab (39.5% versus 12.5%, P < 0.01; 45.5% versus 14.3%, P = 0.02).

  Conclusions: The clinical utility of comprehensive measurement of autoimmune disease-related Abs before introduction of ICI therapy was limited for predicting irAE. However, Tg and TPO Abs were risk factors as regards the development of ICI-induced thyroid dysfunction.

  Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

• How I treat malignant pleural mesothelioma. G. Viscardi, R. Di Liello, F. Morgillo. 2020;4(Suppl 2):e000669. Review PubMed · Publisher · Free full text

  Abstract

  Malignant pleural mesothelioma is a rare and aggressive malignancy mostly associated with occupational asbestos exposure. Prognosis is poor and only highly selected patients may benefit from aggressive surgical management, also as part of a multimodal approach. In advanced disease, the combination of pemetrexed and platinum remains the only established treatment, while efficacy evidence of second line chemotherapy is lacking. Thus, a deeper knowledge of biology of the disease and more effective treatments are urgently needed. Refer to specialised centres with multidisciplinary expertise is mandatory, as well as inclusion of patients in clinical trials is advisable whenever possible. In all stages of disease focus on symptoms control is paramount.

  © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ on behalf of the European Society for Medical Oncology.

2010s

• Indolent peritoneal mesothelioma: PI3K-mTOR inhibitors as a novel therapeutic strategy. S.O. Dolly, C. Migali, N. Tunariu, et al. 2017;2(1):e000101. PubMed · Publisher · Free full text

  Abstract

  Unlabelled: Peritoneal mesothelioma (MPeM) is a scarce abdominal-pelvic malignancy that presents with non-specific features and exhibits a wide clinical spectrum from indolent to aggressive disease. Due to it being a rare entity, there is a lack of understanding of its molecular drivers. Most treatment data are from limited small studies or extrapolated from pleural mesothelioma. Standard treatment includes curative surgery or pemetrexed-platinum palliative chemotherapy. To date, the use of novel targeted agents has been disappointing. Described is the management of two young women with papillary peritoneal mesothelioma with widespread recurrence having received platinum-pemetrexed chemotherapy. Both patients obtained symptomatic and disease benefit with apitolisib, a dual phosphoinositide 3-kinase-mammalian target of rapamycin (PI3K-mTOR) inhibitor for subsequent relapses, with one patient having a partial response for almost 3 years. Both are alive and well 10-13 years from diagnosis.

  Conclusion: These case presentations highlight a subgroup of rare MPeM that behave indolently that is compatible with long-term survival. This series identifies the use of targeted therapies with PI3K-mTOR-based inhibitors as a novel approach, warranting further clinical assessment. Development of prognostic biomarkers is essential to aid identify tumour aggressiveness, help stratify patients and facilitate treatment decisions.

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