Abstract 1405P
Background
High TMB is a promising predictive biomarker for immune checkpoint blockade. Circulating tumor DNA (ctDNA) from plasma is a minimally invasive method that may ease TMB assessment. Prevalence and characteristics of metastatic prostate cancer (mPC) with high TMB is not well described.
Methods
We retrospectively reviewed all patients with mPC who underwent a liquid biopsy within the STING trial, NCT04932525 at Gustave Roussy. Genomic analyses were performed on plasma samples using the FoundationOne Liquid CDx (324 genes) next-generation sequencing assay. H-bTMB was defined with a cutoff >16mut/Mb (Gandara et al., 2018). We aimed to assess the proportion of h-bTMB and its association with clinical characteristics and molecular alterations. For patients with archived available primary tumor tissue, we compared TMB and genomic alterations in liquid and tissue (FoundationOne DX1).
Results
From November 2020 to February 2022, a liquid biopsy was performed in 281 patients with mPC. The median age was 70 years, 90% of patients had metastatic castration-resistant prostate cancer (mCRPC) and 73% had no visceral metastases. The median number of previous systemic therapies was 4 [IQR 2-5]. Overall, 275 patients were evaluable for bTMB. The median bTMB was 4mut/Mb (IQR 1-6), with bTMB>10mut/Mb in 32 (12%) patients and an h-bTMB (>16mut/Mb) in 15 (5%). Clinical characteristics were comparable between patients with and without h-bTMB. Among patients with h-bTMB, a deleterious alteration was found in BRCA 1/2 in six (40%) patients and in CDK12 in one (7%) patient. Furthermore, 7 (2.5%) patients had a microsatellite instability-high (MSI-h) ctDNA phenotype, including one with bTMB equal to 5mut/Mb. Eighty-five tumor tissue/ctDNA pairs were available for comparison. Among them, 4 patients had h-bTMB while only one displayed tissue TMB>10mut/Mb. Comprehensive genomic analyses will be presented at the meeting.
Conclusions
Only 5% patients had an h-bTMB (with a cutoff >16mut/Mb). H-bTMB was associated with DNA-repair alterations. Prospective studies assessing the relevance and the predictive impact of h-bTMB for immune checkpoint blockade efficacy are undergoing.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Lacroix: Financial Interests, Personal, Advisory Role: Adept Field solutions, AstraZeneca, Bayer, Boehringer, BMS, Lilly, Icomed, Illumina, Genomic Health, MedImmune, Novartis, Pfizer, QualWorld, Taiho Oncology, Roche, Thermofisher, VelaDX; Financial Interests, Personal, Other: Abbot, Amgen, Beckman Couletr, Guardant health, Myriad, Siemens, Healthineer. L. Albiges: Financial Interests, Institutional, Other, Consulting: Astellas, AstraZeneca, BMS, EISAI, Ipsen, Janssen, MSD, Merck, Novartis, Pfizer; Non-Financial Interests, Principal Investigator: Pfizer, BMS, Ipsen, AVEO, AstraZeneca, MSD; Non-Financial Interests, Other, Clinical trial steering committee: Roche, Exelixis; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Other, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology (EAU); Non-Financial Interests, Other, Member of the Kidney Cancer Research Summit scientific committee 2021: Kidney Can; Other, Scientific Committee: BMS France. E. Colomba: Financial Interests, Personal, Advisory Role: Ipsen, BMS, Sanofi, Tesaro, MSD, Eisai, Pfizer, GSK. R. Flippot: Financial Interests, Personal and Institutional, Other: Ipsen, Bayer, MSD, BMS, Astellas, Janssen. N. Naoun: Financial Interests, Personal, Other: Merck, Bayer. A. Patrikidou: Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Advisory Board: Basilea. S. Ponce: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Other: RSD Pharma. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion. Y. Loriot: Financial Interests, Personal, Advisory Board: Merck KGaA, Pfizer, Gilead, Seattle Genetics, Tahio; Financial Interests, Personal, Other, Lectures, Advisory Boards: MSD, AstraZeneca, Astellas, Janssen; Financial Interests, Personal, Other, Lectures, Advisory boards: Roche, BMS; Financial Interests, Institutional, Research Grant: Janssen, Sanofi, MSD, Roche, Celsius; Financial Interests, Institutional, Invited Speaker: Janssen, Pfizer, janssen, MSD, Janssen, Exelexis, AstraZeneca, Pfizer, Merck KGaA, BMS, Astellas, Gilead, Incyte; Financial Interests, Invited Speaker: MSD, Astellas, Gilead/Immunomedics, Tahio; Financial Interests, Personal, Invited Speaker: Basilea; Non-Financial Interests, Member: ESMO, ASCO, AACR; Non-Financial Interests, Other, Scientific Committee: ARC. C. Baldini: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Expert Testimony: MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Invited Speaker: iTeos, AZ, Janssen, Amgen, Bicycle Therapeutics, MSD, Seattle Genetics, Tahio; Non-Financial Interests, Member: ASCO, SIOG, SOFOG, AACR. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Invited Speaker: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. A. Bernard-Tessier: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Other, travel fees: Orion, Bayer; Financial Interests, Institutional, Advisory Board: Novartis; Non-Financial Interests, Principal Investigator: Amgen. All other authors have declared no conflicts of interest.