Abstract
Background
Breast and prostate are in general, less responsive to Immune checkpoint inhibitors (ICIs). Tumor mutation burden (TMB) has emerged as a predictive biomarker of response to ICIs and new technologies for evaluating TMB, including liquid biopsy, are now available. We aimed to investigate the role of blood TMB in predicting response to ICIs and its association with genomics alterations.
Methods
The clinical cohort included metastatic breast and prostate cancer patients treated with an ICI following a bTMB ≥10 mut/Mb. Clinical, genomic, and outcomes data were collected. The Guardant Health genomic database (GHGD) was then queried for patients with breast (N = 7899) or prostate (N = 6093) cancers who had a bTMB of ≥10 and 16 mut/Mb, identified by ctDNA NGS (N = 13,992) for associations of bTMB with genomic alterations.
Results
In the clinical cohort (N = 48), ICI treatment was offered after a median of 3 (1–9) lines of treatment. The median bTMB was 16.4 (10–186) mut/Mb. The median PFS was 3.1 months (95%CI, 1.6–4.6), no difference by MSI/MMR status (p = 0.152). The best response rate (n = 36) was 16.7%; only N = 1/6 in bTMB < 16 mut/Mb. High bMSI was associated with higher bTMB (correlation test, r = 0.66, p < 0.001) in all except one. In the GHGD, patients with bTMB high had significantly more alterations than bTMB low and TP53, PIK3CA, ATM, ESR1, NF1, BRCA2, ARID1A, and APC were the most frequently altered genes.
Conclusions
Blood TMB was associated with bMSI status but did not independently predict ICI benefits in patients with advanced breast and prostate cancer and refractory to standard systemic therapies. Higher bTMB was associated with higher number of genomic alterations with potential treatment implications.