Avelumab plus axitinib in unresectable or metastatic type B3 thymomas and thymic carcinomas (CAVEATT): a single-arm, multicentre, phase 2 trial

Conforti, Fabio; Zucali, Paolo Andrea; Pala, Laura; Catania, Chiara; Bagnardi, Vincenzo; Sala, Isabella; Vigna, Paolo Della; Perrino, Matteo; Zagami, Paola; Corti, Chiara; Stucchi, Sara; Barberis, Massimo; Guerini-Rocco, Elena; Venosa, Benedetta Di; Vincenzo, Fabio De; Cordua, Nadia; Santoro, Armando; Giaccone, Giuseppe; Pas, Tommaso Martino De

doi:10.1016/s1470-2045(22)00542-3

Cited by 28 publications

(32 citation statements)

References 23 publications

(42 reference statements)

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“…48,50 In contrast, response rates to avelumab and axitinib in B3 thymoma and thymic carcinoma patients did not differ by PD-L1 expression although there was a positive association with higher TMB. 52 TP53 mutations were found more frequently in patients with low or no PD-L1 expression than in patients with high PD-L1 expression, whereas patients with a CYLD mutation had high PD-L1 expression. 48 Coexpression of TP53 and BAP1 mutations were noted in a patient with a poor response to ICB.…”

Section: Biomarkers Of Response and Toxicity In Tet Patients Treated ...mentioning

confidence: 90%

Understanding the landscape of immunotherapy in thymic epithelial tumors

Maniar

Loehrer

2023

Cancer

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Thymic epithelial tumors (TETs) are a rare group of malignancies arising from the thymus. Surgery remains the foundation of treatment for patients with early‐stage disease. Limited treatment options are available for the treatment of unresectable, metastatic, or recurrent TETs and are associated with modest clinical efficacy. The emergence of immunotherapies in the treatment of solid tumors has generated significant interest in understanding their role in TET treatment. However, the high rates of comorbid paraneoplastic autoimmune disorders, particularly in thymoma, have tempered expectations regarding the role of immune‐based therapies. Clinical studies of immune checkpoint blockade (ICB) in thymoma and thymic carcinoma have revealed higher frequencies of immune‐related adverse events (IRAEs) and limited efficacy. Despite these setbacks, the growing understanding of the thymic tumor microenvironment and systemic immune system has advanced the understanding of these diseases and provided opportunities for novel immunotherapy modalities. Ongoing studies are evaluating numerous immune‐based treatments in TETs with the goal of improving clinical efficacy and mitigating IRAE risk. This review will provide insight into the current understanding of the thymic immune microenvironment, outcomes of previous ICB studies, and review treatments currently being explored for the management of TET.

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Section: Biomarkers Of Response and Toxicity In Tet Patients Treated ...mentioning

confidence: 90%

Understanding the landscape of immunotherapy in thymic epithelial tumors

Maniar

Loehrer

2023

Cancer

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“…A second cohort investigating the combination of nivolumab plus ipilimumab is currently enrolling patients ( ClinicalTrials.gov : NCT03134118). Recently published results from a phase II study in the same population (n=32; 84% with thymic carcinoma) exploring the combination of the tyrosine kinase inhibitor axitinib with the anti-PD-L1 monoclonal antibody avelumab showed an overall response rate of 34%, with a 12% rate of serious adverse events, including grade 3 or 4 polymyositis [ 130 ].…”

Section: Thymic Epithelial Tumoursmentioning

confidence: 99%

Rare thoracic cancers: a comprehensive overview of diagnosis and management of small cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumours

et al. 2023

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Despite the progress in outcomes seen with immunotherapy in various malignancies, including nonsmall cell lung cancer, the benefits are less in small cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumours. New effective treatment options are needed, guidedviamore in-depth insights into the pathophysiology of these rare malignancies. This review comprehensively presents an overview of the clinical presentation, diagnostic tools, staging systems, pathophysiology and treatment options for these rare thoracic cancers. In addition, opportunities for further improvement of therapies are discussed.

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“…So far, three immune-checkpoint inhibitors have been tested in TETs: pembrolizumab, avelumab, and nivolumab [ 10 , 11 , 134 , 135 , 136 , 137 ]. In seminal work by Giaccone et al, pembrolizumab showed a 22.5% response rate in thymic carcinomas, although up to 15% of patients experienced severe autoimmune toxicity [ 10 ].…”

Section: Diagnostic and Therapeutic Approachesmentioning

confidence: 99%

“…Avelumab has also shown a promising effect in TETs, either alone or in association with axitinib [ 136 , 142 ]. As regard to combination therapies, three currently ongoing phase II trials are evaluating the putative synergic effects of immune-checkpoint inhibitors and multikinase inhibitors, namely, avelumab plus axitinib and pembrolizumab plus lenvatinib in pre-treated B3 thymomas and thymic carcinomas [ 135 , 136 ], and pembrolizumab plus sunitinib in thymic carcinomas (NCT03463460). Another trial (NCT02364076) is evaluating the association of pembrolizumab with the indoleamine 2–3dioxygenase (IDO)-inhibitor epacadostat.…”

Section: Diagnostic and Therapeutic Approachesmentioning

confidence: 99%

Thymic Epithelial Tumors: An Evolving Field

Kuhn

Pescia

Mendogni

et al. 2023

Life

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Despite their rarity, thymic epithelial tumors (TETs) have attracted much interest over the years, leading to an impressive number of histological and staging classifications. At present, TETs are divided by the WHO classification into four main subtypes: type A, type AB, and type B thymomas (subdivided into B1, B2, and B3), and thymic carcinomas, going from the more indolent to the most aggressive ones. Among many debated staging proposals, the TNM and the Masaoka–Koga staging systems have been widely accepted and used in routine practice. The four-tiered histological classification is symmetrically mirrored by the molecular subgrouping of TETs, which identifies an A-like and an AB-like cluster, with frequent GTF2I and HRAS mutations; an intermediate B-like cluster, with a T-cell signaling profile; and a carcinoma-like cluster comprising thymic carcinomas with frequent CDKN2A and TP53 alterations and a high tumor molecular burden. Molecular investigations have opened the way to tailored therapies, such as tyrosine kinase inhibitors targeting KIT, mTOR, and VEGFR, and immune-checkpoints that have been adopted as second-line systemic treatments. In this review, we discuss the crucial events that led to the current understanding of TETs, while disclosing the next steps in this intriguing field.

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Avelumab plus axitinib in unresectable or metastatic type B3 thymomas and thymic carcinomas (CAVEATT): a single-arm, multicentre, phase 2 trial

Cited by 28 publications

References 23 publications

Understanding the landscape of immunotherapy in thymic epithelial tumors

Understanding the landscape of immunotherapy in thymic epithelial tumors

Rare thoracic cancers: a comprehensive overview of diagnosis and management of small cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumours

Thymic Epithelial Tumors: An Evolving Field

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