E pluribus unum.

The first-of-its-kind 2017 tissue-agnostic FDA approval of pembrolizumab for any tumor with high microsatellite instability (MSI-H) or deficiency in mismatch repair (dMMR) opened the door for the first potential therapeutic indication for tumor profiling of prostate cancer. What remains unknown are both the frequency of MSI-H/dMMR and its true predictive power in prostate cancer, a malignancy that's had pretty notoriously bad responses to PD-1 axis inhibition. So where better to turn than to a prospective observational genomic series at MSKCC. Over a period of 3 years, adequate next-generation sequencing was performed on prostate tumors from over 1K patients, among whom only 32 (3%) were MSI-H or dMMR. Of these, 11 developed castration-resistance at which point they received PD-1 axis inhibition, and 6 experienced a drop of >50% in PSA and 4 a drop >99% with 5 still controlled on therapy. TBL: MSI-H/dMMR does appear to predict response to PD-1 axis inhibition in prostate cancer; it just doesn’t happen that often. | Abida, JAMA Oncol 2018


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