1919P - Clinical actionability of germline alterations in pleural mesothelioma: Results from a multicentric study

Background

Around 10% of patients affected by pleural mesothelioma (PM) carry a germline pathogenic variant (PV). Some of these variants might be therapeutically exploited using targeted agents. The goal of this study is to clinically characterize the PM patients that carry germline mutations.

Methods

A blood sample was drawn and germline NGS testing was performed using panel testing, that included 96-107 genes involved in inherited cancer syndromes. Fifty-three of the analyzed genes were involved in DNA repair. The identified PVs were confirmed by Sanger sequencing [1-3]. The collection of extensive clinical data of the mutated patients is ongoing.

Results

Totally, 23/213 patients (10.8%) carried a germline PV. The most frequently mutated genes are BAP1 (6/23-26%), CDKN2A, SLX4 and BRCA1 (2/23 each, 8.6%), while 1 germline PV was found for ATM, BRCA2, BRIP1, CHEK2, FANCC, FANCF, FANCI, FLNC, PALB2, SBDS, VHL, XPC (1/23-4.3%). Twelve genes were involved in Homologous Recombination Repair.Of these mutations BRCA1 and BRCA2 germline PVs are an ESCAT tier IIIa (13% of the germline PV carriers, 1.4% overall) for Olaparib, while ATM mutations might be considered an ESCAT tier IV for tazemetostat. Histology is epithelioid in 150, biphasic in 34, sarcomatoid in 22, unknown in 2 and not available in 5 patients.

Conclusions

The identification of PM patients carrying germline PVs may enrich the therapeutic landscape for PM. Analyses on the associations of PV and clinical variables are ongoing, putting in context the hypothetic predictive value of these alterations on conventional treatments for PM.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

L. Cerbone: Non-Financial Interests, Personal, Other, Travel and accommodation: Pierre Fabre. F. Grosso: Financial Interests, Personal, Advisory Role: BMS, MSD, Pierre Fabre, PharmaMar, Novocure, Novartis; Financial Interests, Personal, Speaker’s Bureau: Novocure. All other authors have declared no conflicts of interest.