72P - MDM alterations in patients with advanced or metastatic cancers

Background

Oncogenic alterations in MDM represent important therapeutic targets in various type of cancer. We aimed to assess the prevalence of its incidence together with p53 status in advanced solid tumors based on commercially available NGS panel and to monitor patients’ clinical pathway care.

Methods

Between 2019-2022, 740 patients were included for molecular testing in the Center of Excellence for Precision Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. The population with MDM alterations was extracted for this analysis. We analyzed their therapeutic options over the years, access to clinical trials and impact on patients’ survival.

Results

In our cohort, 48 patients (6.5%) had been identified with MDM alterations as amplification (38), rearrangements (5), and SNPs (5). The most common histology were sarcomas (22), cholangiocarcinoma (3), gastric cancer (3), colorectal cancer (3), breast cancer (3), ovarian cancer (2), salivary gland cancer (2), melanoma (2), urothelial cell carcinoma (2), other (6). In sarcoma, 20/22 had amplification of MDM2, 6/22 rearrangements (MDM2-PPFIA2 rearrangement, MDM2-CSMD1 rearrangement, MDM2-EYS rearrangement) and SNPs (I388V and R332P). The predominant histology types were liposarcomas 14 (64%), sporadically MDM changes were found in rhabdomyosarcoma, osteosarcoma, angiosarcoma, leiomyosarcoma, undifferentiated spindle cell sarcoma and malignant peripheral nerve sheath tumour.

Conclusions

The detection of MDM alterations allows for access to targeted therapies, especially in sarcomas, which may be an important therapeutic option in these rare cancers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

I. Lugowska: Financial Interests, Personal, Invited Speaker, The reports of clinical trials: Roche, BMS, Macrogenics, Amgen; Financial Interests, Institutional, Other, Research grants: Roche; Financial Interests, Institutional, Other, Research grant: Agenus; Financial Interests, Personal and Institutional, Invited Speaker: Agenus, Roche, BMS, Janssen, Astra, Incyte, Macrogenics, Checkpoint Inhibitors, Celon, Pfizer, MSD, DeBio; Non-Financial Interests, Personal, Project Lead: MSCI; Non-Financial Interests, Personal, Advisory Role, Board Member: EORTC. H.M. Kosela Paterczyk: Financial Interests, Personal, Research Grant: Roche, ABM; Financial Interests, Personal, Invited Speaker: BMS, MSD, Pierre Fabre; Financial Interests, Personal, Principal Investigator: Rain. M. Chelstowska: Financial Interests, Personal, Research Grant: Roche, ABM, MSD, BMS, Pfizer, Janssen. A. Dawidowska: Financial Interests, Personal, Research Grant: Roche, MSD, ABM, BMS, Pfizer, Janssen. S. Jaczewska: Financial Interests, Personal, Research Grant: Roche, BMS, ABM, Pfizer; Financial Interests, Personal, Invited Speaker: Janssen. A. Napora, A. Tysarowski: Financial Interests, Personal, Research Grant: Roche. P. Rutkowski: Financial Interests, Personal, Invited Speaker, Honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis; Financial Interests, Institutional, Research Grant for ISS: Pfizer; Financial Interests, Institutional, Funding, Research Grant: BMS; Non-Financial Interests, Personal, Invited Speaker: Polish Society of Surgical Oncology; Non-Financial Interests, Personal, Officer: ASCO; Non-Financial Interests, Personal, Invited Speaker, President Elect: Polish Oncological Society. All other authors have declared no conflicts of interest.