Abstract 4928: Relationship between protein biomarkers of potential chemotherapy response and microsatellite status, tumor mutational burden, and PD-L1 expression in patients with cancer

Abstract

Abstract Introduction: Chemotherapy and checkpoint inhibitor immunotherapies are increasingly used in combinations. We determined associations between the presence of anti-PD-1/PD-L1 therapeutic biomarkers and protein markers of potential chemotherapy response. Methods: Data was extracted from a clinical-grade testing database (Caris Life Sciences; Feb 2015 - Nov2017): immunotherapy response markers (microsatellite instability high (MSI-H) and tumor mutation burden-high (TMB-H) (by next generation sequencing (NGS)) and PD-L1 protein expression (immunohistochemistry); and protein chemotherapy response markers (ERCC1, TOPO1, TOP2A, TS, TUBB3, RRM1, and MGMT; immunohistochemistry). Relationships were determined by the Mantel-Haenszel chi-squared test or Fischer’s exact tests. Results: Overall, 28,034 patients (40 tumor types) were assessed. MSI-H was found in 3.3% of patients, TMB-H, 8.4%, and PD-L1 expression in 11.0% of patients. Based on concurrent biomarker expression, combinations of immunotherapy with platinum (ERCC1 negativity) or with doxorubicin, epirubicin, or etoposide (TOP2A positivity), have a higher probability of response while combinations with irinotecan or topotecan (TOPO1 positivity), with gemcitabine (RRM1 negativity), and fluorouracil, pemetrexed, or capecitabine (TS negativity) may be of less benefit. The potential for immunotherapy and taxane (TUBB3 negativity) combinations is present for MSI-H but not TMB-H or PD-L1-expressing tumors; for temozolomide and dacarbazine (MGMT negative), PD-L1 is frequently co-expressed, but MSI-H and TMB-H are not associated. Conclusion: Protein markers of potential chemotherapy response along with NGS for immunotherapy response markers can help support rational combinations as part of a precision oncology approach. Citation Format: Mina Nikanjam, David Arguello, Zoran Gatalica, Donald A. Barkauskas, Razelle Kurzrock. Relationship between protein biomarkers of potential chemotherapy response and microsatellite status, tumor mutational burden, and PD-L1 expression in patients with cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4928.