Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in

Nowak, Anna K.; Lesterhuis, W. Joost; Kok, Peey‐Sei; Brown, Chris; Hughes, Brett; Karikios, Deme; John, Thomas; Kao, Steven; Leslie, Connull; Cook, Alistair; Pavlakis, Nick; Briscoe, Karen; O’Byrne, Kenneth J.; Karapetis, Christos S.; Lam, Wei-Sen; Langford, Ailsa; Yip, Sonia; Stockler, Martin R.

doi:10.1016/s1470-2045(20)30462-9

Cited by 119 publications

(96 citation statements)

References 27 publications

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“…The solution to these challenges lies with the investigation of reliable predictive biomarkers, which will allow the selection of appropriate candidates for improving the benefits of ICI therapy. The role of chemo-immunotherapy combinations (78) and dual blockage immune checkpoint inhibition (77) seems more promising, but the best combination of ICIs has not yet been determined. Because MPM is also characterized as an extremely inflammatory tumor, further studies focusing on MPM cells and epigenetic alterations may lead to the identification of reliable biomarkers.…”

Section: Resultsmentioning

confidence: 99%

Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors–Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment

et al. 2020

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Malignant pleural mesothelioma (MPM) is strongly associated with occupational or environmental asbestos exposure and arises from neoplastic transformation of mesothelial cells in the pleural cavity. The only standard initial treatment for unresectable MPM is combination chemotherapy with cisplatin (CDDP) and pemetrexed (PEM). Further, CDDP/PEM is the only approved regimen with evidence of prolonged overall survival (OS), although the median OS for patients treated with this regimen is only 12 months after diagnosis. Thus, the development of new therapeutic strategies has been investigated for approximately 20 years. In contrast to recent advances in personalized lung cancer therapies, diagnostic and prognostic biomarker research has just started in mesothelioma. Epigenetic alterations include DNA methylation, histone modifications, and other chromatin-remodeling events. These processes are involved in numerous cellular processes including differentiation, development, and tumorigenesis. Epigenetic modifications play an important role in gene expression and regulation related to malignant MPM phenotypes and histological subtypes. An immune checkpoint PD-1 inhibitor, nivolumab, was approved as second-line therapy for patients who had failed initial chemotherapy, based on the results of the MERIT study. Various clinical immunotherapy trials are ongoing in patients with advanced MPM. In this review, we describe recent knowledge on epigenetic alterations, which might identify candidate therapeutic targets and immunotherapeutic regimens under development for MPM.

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Section: Resultsmentioning

confidence: 99%

Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors–Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment

et al. 2020

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“…Combination of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) provides a survival benefit over chemotherapy in malignant pleural mesothelioma (14). Platinum-based chemotherapies may synergize with ICB, with single arm studies showing that combination chemo-immunotherapy reduces tumor burden and shows promising progression-free and overall survival outcomes for mesothelioma (17)(18)(19). In addition, complete tumor regression has been observed in some NSCLC (20)(21)(22) and SCLC (23)(24)(25) patients treated with chemo-immunotherapy.…”

Section: There Is An Urgent Need To Develop Biomarkers Of Response To Immune Checkpoint Blockadementioning

confidence: 99%

Malignant Pleural Effusions—A Window Into Local Anti-Tumor T Cell Immunity?

Principe¹,

Kidman²,

Lake³

et al. 2021

Front. Oncol.

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The success of immunotherapy that targets inhibitory T cell receptors for the treatment of multiple cancers has seen the anti-tumor immune response re-emerge as a promising biomarker of response to therapy. Longitudinal characterization of T cells in the tumor microenvironment (TME) helps us understand how to promote effective anti-tumor immunity. However, serial analyses at the tumor site are rarely feasible in clinical practice. Malignant pleural effusions (MPE) associated with thoracic cancers are an abnormal accumulation of fluid in the pleural space that is routinely drained for patient symptom control. This fluid contains tumor cells and immune cells, including lymphocytes, macrophages and dendritic cells, providing a window into the local tumor microenvironment. Recurrent MPE is common, and provides an opportunity for longitudinal analysis of the tumor site in a clinical setting. Here, we review the phenotype of MPE-derived T cells, comparing them to tumor and blood T cells. We discuss the benefits and limitations of their use as potential dynamic biomarkers of response to therapy.

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“…Later study data indicated durvalumab alone or combined with tremelimumab improved OS and PFS compared with standard of care as third-line or later treatment ( Planchard et al, 2020 ). Numerous clinical trials are investigated in HNSCC ( Ferris et al, 2020 ), TNBC ( Loibl et al, 2019 ), HER2-positive breast cancer ( Chia et al, 2019 ), gastric and GEJ adenocarcinoma ( Kelly et al, 2020 ), lymphoma ( Herrera et al, 2020 ) and pleural mesothelioma ( Nowak et al, 2020 ).…”

Section: Clinical Use Efficacy and Safetymentioning

confidence: 99%

Comparisons of Underlying Mechanisms, Clinical Efficacy and Safety Between Anti-PD-1 and Anti-PD-L1 Immunotherapy: The State-of-the-Art Review and Future Perspectives

2021

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Over the past decade, diverse PD-1/PD-L1 blockades have demonstrated significant clinical benefit in across a wide range of tumor and cancer types. With the increasing number of PD-1/PD-L1 blockades available in the market, differences between the clinical performance of each of them started to be reported. Here, we provide a comprehensive historical and biological perspective regarding the underlying mechanism and clinical performance of PD-1/PD-L1 blockades, with an emphasis on the comparisons of their clinical efficacy and safety. The real-world evidence indicated that PD-1 blockade may be more effective than the PD-L1, though no significant differences were found as regards to their safety profiles. Future head-to-head studies are warranted for direct comparison between them. Finally, we summarize the yet to be elucidated questions and future promise of anti-PD-1/PD-L1 immunotherapy, including a need to explore novel biomarkers, novel combinatorial strategies, and their clinical use on chronic infection.

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Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in

Cited by 119 publications

References 27 publications

Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors–Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment

Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors–Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment

Malignant Pleural Effusions—A Window Into Local Anti-Tumor T Cell Immunity?

Comparisons of Underlying Mechanisms, Clinical Efficacy and Safety Between Anti-PD-1 and Anti-PD-L1 Immunotherapy: The State-of-the-Art Review and Future Perspectives

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