Abstract 512P
Background
Patients with advanced solid tumors having TMB-H status are candidates for treatment with immune checkpoint inhibitors (ICI). We hypothesized that TMB-H solid tumors may have genomic alterations profiles that differ from those without TMB-H.
Methods
We conducted a retrospective analysis of 194 advanced cancer patients with test results from commercial tissue (TissueNextTM) and/or ctDNA (Guardant360®) next-generation sequencing assays from a single center in India. For 110 patients, both tissue and ctDNA results were available (Arm A); 84 had only ctDNA results (Arm B). TMB-H was defined as >10 muts/Mb in tissue or >16 muts/Mb in ctDNA. Microsatellite instability (MSI) and alterations of specific genes were also assessed.
Results
TMB-H was detected in 38/194 patients (19.5%; 17.3% Arm A, 22.6% Arm B) predominantly males (23 males vs 15 females). TMB was not evaluable for 51 patients (39 arm A, 12 in arm B). The greatest frequencies of TMB-H were observed in lung 8/36 (22.2%), colorectal 8/19 (42.1%), breast 3/25 (12%), prostate 3/12 (25%), and hepatocellular cancers 3/7 (42.8%). Compared to 105 low TMB tumors, TMB-H tumors had higher mutation rates for APC (32 vs 9%), MTOR (26 vs 6%), BRCA1 (21 vs 2%), BRCA2 (18 vs 6%), MSH6 (16 vs 1%), MSH2 (13 vs 1%), FGFR3 (13 vs 2%), AR (16 vs 5%), and NTRK2 (13 vs 3%) and more frequent amplification of FGFR1 (18 vs 6%), EGFR (16 vs 10%), PIK3CA (5 vs 1%), and ERBB2 (8 vs 4%). MSI-H co-occurred in 3 TMB-H cases.
Conclusions
We found TMB-H in 19% of our study cohort of advanced cancers with higher alterations/sample detected using ctDNA compared to Tissue (15 vs 10 Mut/sample respectively). TMB-H tumors had a significant enrichment for alterations in genes encoding proteins involved in the DNA repair pathway and growth factor receptor signal transduction. Combining immune checkpoint inhibitors with targeted therapies aimed at specific pathways could be further explored to potentially enhance outcomes for patients with solid tumors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
N. Rohatgi: Financial Interests, Personal and Institutional, Advisory Role: Guardant Health. A. Bahl: Financial Interests, Personal, Advisory Role: Guardant Health. R. Bharat, N. Joshi: Financial Interests, Institutional, Full or part-time Employment: Guardant Health. All other authors have declared no conflicts of interest.