Abstract 234P
Background
Squamous Anal carcinoma (SAC), is a rare malignancy with high morbidity and mortality, particularly in metastatic cases. Unfortunately, there have been limited advances in the treatment of SAC patients(pts)in recent years and they are often excluded from precision medicine studies.Our aim is to assess the molecular characteristics derived from tissue and liquid biopsies, in a large cohort of SAC pts.
Methods
We conducted a retrospective review of genomic analysis utilizing the FoundationOne®Liquid CDx and FoundationOne®CDx assays. The data collected included demographics, HPV status, and molecular alterations (MA). Additionally, we performed a comparative analysis between tissue and liquid samples where applicable.
Results
Analysis of 1733 tissue samples (cohort 1) and 140 liquid biopsy samples (cohort 2) with SAC. For cohort 1: 69% (n=1201) were female, 31% (n=532) were male, with a median age of 61 years(y). The majority (n=858; 49.5%) had metastatic disease, and 87% (n=1500) had HPV-positive tumors, the most prevalent HPV subtypes being HPV-16 (n=1315, 75.9%) and HPV-18 (n=62, 3.6%).Liver (n=325, 38 %) and lymph nodes (n=218; 25%) were the most common metastatic sites. The median tissue tumor mutation burden (tTMB) was 4.8 mutations per megabase (mut/Mb), 17.1% (n=296) -tTMB≥10mut/Mb.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%). Interestingly, KMT2D alterations were associated with higher tTMB (median tTMB 7.37 mut/Mb vs 3.75 mut/Mb, p<0.05). All molecular alterations were classified within ESCAT: ESCAT1+2=19.7% (n=341); Escat 3A+3B=39.5%(n=684). PIK3CA alterations were predominantly identified in HPV-16 pts, TP53 alterations in HPV-negative pts and CDKN2A in HPV-6 pts. For cohort 2, the majority were females (n=95, 68%), with a median age of 63 y,median blood TMB (bTMB)-6.3 mut/Mb. The five most alterated genes were as follows: TP53 (n=50,35.7%) PIK3CA (n=25, 35%), KMT2D (n=21,30 %), PTEN (n=21, 30%), and FBWX7 (n=9, 12.9%). All molecular alterations were classified within ESCAT (final version). Data in paired analysis will be presented in the final version.
Conclusions
Molecular profiling could open the opportunity to be included in clinical trials.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Smolenschi: Financial Interests, Institutional, Invited Speaker: Servier, Merck, Roche; Non-Financial Interests, Institutional, Principal Investigator: Astellas, BMS. R. Sharaf: Non-Financial Interests, Institutional, Member: Foundation ONE. A. Hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, Eisai; Financial Interests, Personal, Advisory Board: Basilea, Tahio, 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: AbbVie; Non-Financial Interests, Principal Investigator, CO42216 ; WP42627 ; CO40939: Roche; Non-Financial Interests, Principal Investigator, MCLA-158: Merus; Non-Financial Interests, Principal Investigator, SGNB6A: Seattle Genetics; Non-Financial Interests, Principal Investigator, TAS-120-202: Tahio; 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: 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/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. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Invited Speaker: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. M.P. Ducreux: Financial Interests, Personal, Invited Speaker: Roche, Amgen, Pierre Fabre, Merck KGaA, 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, Invited Speaker: Rafael, Amgen; Financial Interests, Institutional, Funding: Bayer; Other, My wife is head of the oncology business unit in the French Affiliate of Sandoz. C.P. Massard: Other, Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion; Principal/sub-Investigator of Clinical Trials for: AbbVie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo pharmaceuticals, Bayer, BeiGene, Blueprint, BMS, Boehringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 biomedecine, Incyte, Innate Pharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, Lytix Biopharma, Medimmune, Menarini, Merus, MSD, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides AB, Orion, Pfizer, PharmaMar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, Xencor. O. Gjoerup, A. Fine: Non-Financial Interests, Institutional, Member: Foundation ONE. All other authors have declared no conflicts of interest.