Tumor frameshift mutation proportion predicts response to immunotherapy in mismatch repair-deficient prostate cancer.

CONCLUSIONS: Tumor FSP correlated with prolonged efficacy of anti-PD1 treatment among patients with dMMR cancers, and may represent a new biomarker of immune checkpoint inhibitor sensitivity.
IMPLICATIONS FOR PRACTICE: Given the modest efficacy of immune checkpoint inhibition (ICI) in unselected patients with advanced prostate cancer, biomarkers of ICI sensitivity are needed. To facilitate biomarker discovery, we assembled a cohort of patients with DNA mismatch repair-deficient (dMMR) prostate cancer as these patients are enriched for responses to ICI. We observed a high response rate to anti-PD1 therapy in these patients, however these responses were not durable in most patients. Notably, we identified tumor frameshift mutation proportion (FSP) as a novel biomarker that was associated with prolonged response to anti-PD1 therapy in this cohort. This finding was validated in a separate cohort of patients with non-prostatic dMMR cancers of various primary histologies. This works suggests that FSP predicts response to anti-PD1 therapy in dMMR cancers, which should be validated prospectively in larger independent cohorts.
PMID: 33215787 [PubMed - as supplied by publisher]

Source: The Oncologist - November 20, 2020 Category: Cancer & Oncology Authors: Sena LA, Fountain J, Isaacsson Velho P, Lim SJ, Wang H, Nizialek E, Rathi N, Nussenzveig R, Maughan BL, Velez MG, Ashkar R, Larson AC, Pritchard CC, Adra N, Bryce AH, Agarwal N, Pardoll DM, Eshleman JR, Lotan TL, Antonarakis ES Tags: Oncologist Source Type: research