108P - Assessing molecular characteristics in a large cohort of anal squamous cell carcinoma patients

Background

Anal Squamous Cell Carcinoma (aSCC) is a rare malignancy with rising incidence and limited therapeutic options, particularly in advanced stages. This study aims to assess the molecular alterations (MA)derived from tissue and liquid biopsies in a large cohort of aSCC pts.

Methods

We conducted a retrospective review of genomic analysis utilizing the FoundationOne®Liquid CDx and FoundationOne®CDx assays. The patients were divided into two cohorts: tissue and liquid biopsies.

Results

Analysis of 1733 tissue samples (cohort 1) and 140 liquid biopsy samples (cohort 2) from aSCC pts revealed the following main characteristics: cohort 1: the majority of pts were female (69%) with metastatic disease (49.5%), primarily affecting the liver (38%) and lymph nodes (25%), 87% HPV + tumors, with HPV-16 being the most prevalent subtype (75.9%). Cohort 2: pts were mainly females (68%), with metastatic disease and liquid biopsy performed at progression/initial diagnosis. MA: cohort 1: The five most altered genes were as follows: PIK3CA (n=598, 34.5%), KMT2D (n=312, 18%), PTEN (n=227, 13.1%), FBXW7 (n=223, 12.9%), and TP53 (n=208, n=12%). The MA were classified within ESCAT: ESCAT I+II =19.7% (n=341) and ESCAT IIIA+IIIB = 39.5% (n=684) of the alterations. PIK3CA alterations were predominantly identified in HPV-16 pts, TP53 alterations in HPV negative pts, and CDKN2A in HPV-6 pts. Interestingly, KMT2D alterations were associated with higher tumor mutation burden (p<0.05). Cohort 2: the five most alterated genes were as follows: TP53 (n=26, 18.6%), PIK3CA (n=25, 35%), KMT2D (n=21,30 %), PTEN (n=21, 30%), and FBWX7 (n=9, 12.9%). The MA according to ESCAT:ESCAT I+II = 35.0% (n=49) and ESCAT IIIA+IIIB =72.85% (n=102) of the MA. For 46 pts of cohort 2, tumor fraction (TF) was available and was predictive of clinical outcomes. The median overall survival was longer for the 20 pts with a TF<10%, 23 months(m) (95% CI 18-NA m) compared to the 26 pts with a TF≥10%, 7 m (95% CI 3-16 m) (p=0.00044). Data regarding the paired analysis will be presented at the congress.

Conclusions

Systematic molecular profiling of these pts's tumors will improve our understanding in this rare entity. In a significant percentage of cases, it could provide the access to molecules targeting actionable MA.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C. Smolenschi: Financial Interests, Institutional, Invited Speaker: Roche; Non-Financial Interests, Institutional, Advisory Board: Servier; Non-Financial Interests, Institutional, Principal Investigator: BMS; Non-Financial Interests, Personal, Funding: Merck. R. Sharaf: Non-Financial Interests, Personal, Member: Foundation ONE. A. Hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, Eisai, BMS; Financial Interests, Personal, Advisory Board: Basilea, Taiho, Relay Therapeutics, QED Therapeutics, Debiopharm, MSD, Boehringer Ingelheim; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Principal Investigator, M19-345; M21-404: AbbVie; Non-Financial Interests, Principal Investigator, CO42216 ; WP42627 ; CO40939 ; GO44479; GO42216: Roche; Non-Financial Interests, Principal Investigator, MCLA-158; MCLA-128: Merus; Non-Financial Interests, Principal Investigator, SGNB6A: Seatle Genetics; Non-Financial Interests, Principal Investigator, TAS-120-202: Taiho; Non-Financial Interests, Principal Investigator, Krystal-10: Mirati; Non-Financial Interests, Principal Investigator, ADP-0033: Adaptimmune; Non-Financial Interests, Principal Investigator, ACT16902: Sanofi; Non-Financial Interests, Principal Investigator, C4201002; SGNB6A: Pfizer; Non-Financial Interests, Principal Investigator, RLY-4008: Relay Therapeutics; Non-Financial Interests, Principal Investigator, CC-90011: Celgene/BMS; Non-Financial Interests, Principal Investigator, Loxo-IDH; Loxo-RAS: Loxo/Lilly; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator, SN-201 study: Sotio; Non-Financial Interests, Principal Investigator, Tropics-03: Gilead; Non-Financial Interests, Principal Investigator, BI1403: Boehringer Ingelheim; Non-Financial Interests, Principal Investigator, CA120-1001: BMS. V. Boige: Financial Interests, Personal, Advisory Board: Bayer, Merck Serono, BMS, Roche; Financial Interests, Personal, Invited Speaker: MSD, Ipsen; Financial Interests, Institutional, Funding: Merck Serono. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Coordinating PI: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. L. Benhaim: Financial Interests, Personal, Advisory Board, Proctor for intuitive Surgery: Intuitive Surgery; Financial Interests, Personal, Advisory Board, Participation to advisory board once a year with Bristol Myers Squibb: BMS; Financial Interests, Personal, Invited Speaker, Participation as a speaker to the: Merck; Financial Interests, Personal, Stocks/Shares, 0.03% in Methyx DX Start-up: Methys DX. A. Bayle: Financial Interests, Personal, Advisory Board, ASCO 2022 & ESMO 2023: Sanofi; Financial Interests, Personal, Invited Speaker, Health Economics conference: Roche; Financial Interests, Personal, Other, Expert at the Commission for the Evaluation of Diagnostic, Prognostic and Predictive Health Technologies: HAS (French National Authority for Health); Other, Transportation and accommodation support for the ASCO 2023 Congress: Pfizer. M.P. Ducreux: Financial Interests, Personal, Invited Speaker: Roche, Amgen, Pierre Fabre, Merck Kga, Pfizer, Bayer, Lilly, Servier, MSD, BeiGene; Financial Interests, Personal, Advisory Board: Roche, Basilea, Pierre Fabre, Boehringer Ingelheim, Rafael, Servier, Zymeworks, Ipsen, Bayer, HalioDX, Lilly, GSK, Daiichi Sankyo, MSD, Servier, BeiGene; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Funding, Partial funding of a trial evaluating the role of bevacizumab in NET: Roche; Financial Interests, Institutional, Funding, Partial funding of a trial evaluating the role of steptozotocin in NET: Keocyt; Financial Interests, Institutional, Local PI: Rafael, Amgen; Financial Interests, Institutional, Funding: Bayer; Other, My wife is head of the oncology business unit in the French Affiliate of Sandoz: Sandoz France. D. Vasseur: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche. All other authors have declared no conflicts of interest.