Abstract 75P
Background
Immunotherapy has revolutionized the management of several types of cancers. Recently, pembrolizumab was granted FDA approval for patients with recurrent and/or metastatic cancers with TMB exceeding 10 mutations/Mb assessed by the FoundationOneCDx assay. One major challenge is to reproduce the TMB results obtained by FoundationOne (FO) using other sequencing panels. Based on the experience of Institut Curie (IC) Molecular Tumor Board, we assessed and compared TMB according to both IC and FO algorithms.
Methods
Using an in-house 571 genes NGS panel spanning 1.6 Mb of coding sequence, we assessed TMB in 328 FFPE solid tumor samples from 34 different cancer types applying both in-house IC and FO algorithms.
Results
Main cancer types were breast (19%), sarcoma (17%), ovarian (10%) and colorectal cancers (9%). Median TMB values obtained with the FO algorithm were significantly higher compared to the ones obtained with IC algorithm (median of 46.0 mutations/Mb versus 9.5 mutations/Mb respectively; p<0.0001 using paired Wilcoxon nonparametric test).
Conclusions
The application of FO algorithm for the assessment of TMB using IC NGS large panel gave significantly higher TMB values, suggesting that the FDA-approved FO threshold (10 mut/Mb) cannot be transposed to all panels. Further studies are required to validate these results in cohorts treated by immunotherapy. A collective effort to standardize and make TMB calculation methods accessible for different stakeholders is key. C. Dupain and T. Gutman contributed equally and should be considered co-first authors. N. Servant, M. Kamal and J. Masliah-Planchon contributed equally and should be considered co-last authors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Institut Curie.
Funding
Institut Curie.
Disclosure
C. Le Tourneau: Non-Financial Interests, Institutional, Advisory Board: MSD; Non-Financial Interests, Institutional, Advisory Board: BMS; Non-Financial Interests, Institutional, Advisory Board: Merck Serono; Non-Financial Interests, Institutional, Advisory Board: GSK; Non-Financial Interests, Institutional, Advisory Board: Amgen; Non-Financial Interests, Institutional, Advisory Board: Novartis; Non-Financial Interests, Institutional, Advisory Board: Roche; Non-Financial Interests, Institutional, Advisory Board: Rakuten; Non-Financial Interests, Institutional, Advisory Board: Seattle Genetics; Non-Financial Interests, Institutional, Advisory Board: Nanobiotix; Non-Financial Interests, Institutional, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.