American Association for Cancer Research
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Supplementary Data S2 from Validation of Immunotherapy Response Score as predictive of pan-solid tumor anti-PD-1/PD-L1 benefit

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posted on 2023-07-03, 14:20 authored by Benjamin J Bulen, Nickolay A Khazanov, Daniel H. Hovelson, Laura E Lamb, Marc Matrana, Mark E Burkard, Eddy Shih-Hsin Yang, William J. Edenfield, Elizabeth Claire Dees, Adedayo A. Onitilo, Gary L Buchschacher, Alan M Miller, Benjamin M. Parsons, Timothy R. Wassenaar, Jennifer M. Suga, Robert D Siegel, William Irvin, Suresh Nair, Jennifer N. Slim, Jamal Misleh, Jamil Khatri, Gregory A Masters, Sachdev Thomas, Malek M. Safa, Daniel M. Anderson, Jonathan Mowers, Anna C Dusenbery, Stephanie Drewery, Komal Plouffe, Travis Reeder, Hana Vakil, Lynnae Patrias, Amanda Falzetta, Ryan Hamilton, Kat Kwiatkowski, D. Bryan Johnson, Daniel R Rhodes, Scott A. Tomlins

Supplementary Data S2 shows the clinical and molecular data for the monotherapy validation cohort



Immunotherapy Response Score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PD-L1 (PD-[L]1) monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) vs. -Low (-L) groups. Associations with real-world progression free survival (rwPFS) and overall survival (OS) were determined by Cox proportional hazards (CPH) modeling. Those with available PD-L1 immunohistochemistry treated with anti-PD-(L)1 with or without chemotherapy were separately assessed. Patients treated with PD-(L)1 and/or chemotherapy (five relevant tumor types) were assigned to three IRS groups (IRS-L divided into IRS-Ultra-Low [-UL] and Intermediate-Low [-IL] and similarly assessed. In the 352 patient anti-PD-(L)1 monotherapy validation cohort (31 tumor types), IRS-H vs. IRS-L patients had significantly longer rwPFS and OS. IRS significantly improved CPH associations with rwPFS and OS beyond microsatellite instability (MSI)/TMB alone. In a 189 patient (10 tumor types) PD-L1 IHC comparison cohort, IRS, but not PD-L1 IHC nor TMB, was significantly associated with anti-PD-L1 rwPFS. In a 1,103-patient cohort (from five relevant tumor types), rwPFS did not significantly differ in IRS-UL patients treated with chemotherapy vs. chemotherapy plus anti-PD-(L)1, nor in IRS-H patients treated with anti-PD-(L)1 vs. anti-PD-(L)1 + chemotherapy. IRS associations were consistent across subgroups, including both Europeans and non-Europeans. These results confirm the utility of IRS utility for predicting pan-solid tumor PD-(L)1 monotherapy benefit beyond available biomarkers and demonstrate utility for informing on anti-PD-(L)1 and/or chemotherapy treatment.

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