Abstract 165P
Background
Pleural mesothelioma (PM) is a rare disease with a poor prognosis, often diagnosed at advanced stage. Chemotherapy traditionally addresses unresectable cases; recent phase III trials emphasize the emerging role of immunotherapy (IO). Nevertheless, predictive and prognostic factors for IO remain elusive. This study aimed to assess clinical and molecular determinants that could impact the outcome of IO-treated PM patients (pts).
Methods
We retrospectively analysed data from 24 unresectable PM pts treated with at least one cycle of IO based treatment in any line at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan from March 2018 to December 2023. Next Generation Sequencing analysis (OncomineTM Comprehensive Assay Plus, FoundationOne®CDx or OmniSeq INSIGHT®) was performed. Tumor mutational burden (TMB) was calculated using IonReporter v5.18 software on non-synonymous mut of exonic region >1 Mb. Cox regression models and χ2 tests evaluated associations, Kaplan-Meier estimated the survival curves.
Results
Median age at diagnosis was 67 years, predominantly male (58%). Epithelioid histology was the most common (67%), followed by biphasic (29%) and sarcomatoid (4%). With a median follow up of 26,2 months (mo), median IO progression free survival was 7,85 mo (95% CI 4,4-27,85 mo). The majority of pts were referred to our centre after exhausting standard of care therapies, possibly contributing to the noteworthy median overall survival (mOS) of 27,5 mo. The most frequent somatic mutations were BAP1 (29%), NF2 (17%), FANCA (17%), SNCAIP (17%), CDNK2A (12%), PIK3CA (12%), ATR (12%) and ATM (12%). The median number of gene alterations was 9 and the median TMB was 3.9 mut/Mbp. No statistically significant associations were found among the somatic mutations, the main clinical (age, gender, smoking status, asbestos exposure) or pathological (histology, TMB) variables, and outcome. There was a trend suggesting a potential association between BAP1 loss and mOS (p= 0.13).
Conclusions
Our study did not identify predictive or prognostic factors for IO outcomes in unresectable PM, emphasizing the complexity and heterogeneity of PM. Further research with larger cohorts is crucial to unveil biomarkers in this setting.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Brambilla: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Other: Lilly. S. Manglaviti: Financial Interests, Personal, Other: Italfarmaco, Sanofi, MSD. A. Prelaj: Financial Interests, Personal, Other, Training of personnel: AstraZeneca, Italfarma; Financial Interests, Personal, Invited Speaker, THE HIVE PROJECT: Discussant: Roche; Financial Interests, Personal, Advisory Board, Advisory board in Lung Cancer project: BMS; Financial Interests, Personal, Other, travel grant: Janssen; Financial Interests, Personal, Advisory Board: Janssen, AstraZeneca; Financial Interests, Personal, Invited Speaker: MEDSIR; Financial Interests, Institutional, Invited Speaker: Bayer, BMS, AstraZeneca, Lilly, MSD, SPECTRUM. C. Proto: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, MSD, Roche, Sanofi; Financial Interests, Personal, Other: AstraZeneca, BMS, MSD, Roche. Proto: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, MSD, Roche, Sanofi; Financial Interests, Personal, Other: AstraZeneca, BMS, MSD, Roche. G. Lo Russo: Financial Interests, Personal, Advisory Board: MSD, Novartis, AstraZeneca, BMS, Sanofi, Pfizer, Roche, Lilly, GSK; Financial Interests, Personal, Invited Speaker: Italfarmaco, Sanofi; Financial Interests, Institutional, Other, contribute for meeting organization: Janssen; Financial Interests, Institutional, Other, Contribute for meeting organization: Bayern; Financial Interests, Personal, Other, Travel accommodation: Amgen; Financial Interests, Institutional, Invited Speaker: MSD, BMS, Roche, GSK, Celgene, Novartis, AstraZeneca, Amgen. F.G.M. De Braud: Financial Interests, Personal, Invited Speaker: Amgen, Ambrosetti, Ambrosetti, BMS, Dephaforum, ESO, Healthcare Research & Pharmacoepidemiology, Incyte, MSD, Merck Group, Nadirex, Pfizer, Roche, Sanofi, Seagen, Servier, Accmed, Dynamicom Education, BMS, Basilea Pharmaceutica International AG, Daiichi Sankyo SANKIO Dev. Limited, Exelixis Inc, F.Hoffmann-LaRoche Ltd, IQVIA, Ignyta Operating INC, Janssen-Cilag International NV, Kymab, LOXO Oncology Incorporated, MSD, MedImmune LCC, Merck KGAA, Merck Sharp & Dohme Spa, Novartis, Pfizer, Tesaro; Financial Interests, Personal, Other, Think Thank: MCCann Health; Financial Interests, Personal, Other, Consultant: Mattioli 1885; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other, Consultant Advisory Board: AstraZeneca, BMS, EMD Serono, Incyte, MSD, Menarini, NMS Nerviano Medical Science, Novartis, Pierre Fabre, Roche, Sanofi; Financial Interests, Personal, Other, Consultant Adv Board: Taiho. All other authors have declared no conflicts of interest.