bims-mesote 2024-03-10 papers

Issue of 2024–03–10
two papers selected by
Laura Mannarino, Humanitas Research

Mol Oncol. 2024 Mar 08.

Pleural mesothelioma (PMe): The evolving molecular knowledge of a rare and aggressive cancer.

Manuel Rigon, Luciano Mutti, Michelangelo Campanella.

Mesothelioma is a type of late-onset cancer that develops in cells covering the outer surface of organs. Although it can affect the peritoneum, heart, or testicles, it mainly targets the lining of the lungs, making pleural mesothelioma (PMe) the most common and widely studied mesothelioma type. PMe is caused by exposure to fibres of asbestos, which when inhaled leads to inflammation and scarring of the pleura. Despite the ban on asbestos by most Western countries, the incidence of PMe is on the rise, also facilitated by a lack of specific symptomatology and diagnostic methods. Therapeutic options are also limited to mainly palliative care, making this disease untreatable. Here we present an overview of biological aspects underlying PMe by listing genetic and molecular mechanisms behind its onset, aggressive nature, and fast-paced progression. To this end, we report on the role of deubiquitinase BRCA1-associated protein-1 (BAP1), a tumour suppressor gene with a widely acknowledged role in the corrupted signalling and metabolism of PMe. This review aims to enhance our understanding of this devastating malignancy and propel efforts for its investigation.

Keywords: BAP1 and therapy; asbestos; mesothelioma

DOI: https://doi.org/10.1002/1878-0261.13591

Eur J Cancer. 2024 Mar 01. pii: S0959-8049(24)00129-1. [Epub ahead of print]202 113973

UV1 telomerase vaccine with ipilimumab and nivolumab as second line treatment for pleural mesothelioma - A phase II randomised trial.

Vilde Drageset Haakensen, Åsa Kristina Öjlert, Solfrid Thunold, Saima Farooqi, Anna K Nowak, Wee L Chin, Oscar Grundberg, Weronika Maria Szejniuk, Susana Cedres, Jens Benn Sørensen, Tonje Sofie Dalen, Marius Lund-Iversen, Maria Bjaanæs, Åslaug Helland.

PURPOSE: The NIPU-trial investigates the effect of adding the telomerase vaccine UV1 to treatment with ipilimumab and nivolumab for patients with pleural mesothelioma (PM).
METHODS: In this phase 2 open-label trial, patients with PM progressing after first-line chemotherapy were randomised to receive ipilimumab and nivolumab alone (arm B) or combined with UV1 (arm A). The primary endpoint was progression-free survival (PFS) as determined by BICR. It was estimated that 69 PFS events were needed to detect a hazard ratio (HR) of 0.60 with 80% power and a one-sided alpha level of 0.10.
RESULTS: 118 patients were randomised. The median PFS determined by blinded independent central review (BICR) was 4.2 months (95%CI 2.9-9.8) in arm A and 4.7 months (95%CI 3.9-7.0) in arm B (HR 1.01, 80%CI 0.75-1.36 P = 0.979), after a median follow-up of 12.5 months (95%CI 9.7-15.6). The investigator-determined median PFS was 4.3 months (95%CI 3.0-6.8) in arm A and 2.9 months (95%CI 2.4-5.5) in arm B (HR 0.60, 80%CI 0.45-0.81 P = 0.025). Confirmed objective response rate (ORR) by BICR was 31% in arm A and 16% in arm B (odds ratio 2.44 80%CI 1.35-4.49 P = 0.056). After a median follow-up time of 17.3 months (95%CI 15.8-22.9), the OS was 15.4 months (95%CI 11.1-22.6) in arm A and 11.1 months (95%CI 8.8-18.1) in arm B, (HR 0.73, 80%CI 0.53-1.0, P = 0.197).
CONCLUSION: The primary endpoint was not met. Predefined analyses of response rates are in favour of adding the vaccine.

Keywords: Immunotherapy; Pleural mesothelioma; Telomerase vaccine

DOI: https://doi.org/10.1016/j.ejca.2024.113973