ASCO 2020: Association of Gene Expression with Clinical Outcomes in Patients with Renal Cell Carcinoma Treated with Pembrolizumab in KEYNOTE-427

( KEYNOTE-427 was a single-arm, open-label, phase 2 study of pembrolizumab monotherapy in patients with treatment naïve advanced clear cell RCC (cohort A) and non-clear cell RCC (cohort B). The study schema is shown below.


The objective response in cohort A was 38.2% with 2.7% CRs and a disease control rate of 59.1% (CR/PR/SD ≥6 months). The objective response in cohort B was 24.8% with 4.8% CR and a DCR of 40.6%. This study evaluated the association of baseline RNA-sequencing–based gene expression signatures and DNA alterations in both cohorts to response or resistance to pembrolizumab.

RNA sequencing analysis was completed on 70.9% of patients with ccRCC and 82.4% of patients with nccRCC. A total of 11 gene signatures were defined and finalized before the data was linked to clinical data: T cell inflamed gene expression profile, stromal/EMT/TGF-β, RAS, Angiogenesis, granulocytic myeloid derived suppressor cell (gMDSC), proliferation, MYC, WNT, hypoxia, glycolysis, and mMDSCS (monocytic myeloid derived suppressor cell). Significance was set at 0.10.


Of these 11 signatures, mMDSC and the T-cell inflamed GEP were significantly associated with overall survival for patients with ccRCC. The T cell signature was also significant for nccRCC for response rate but not for overall survival.  


No signature consistent demonstrated a significant association with ORR, PFS, or OS in the 11 exploratory gene signatures tested in this abstract. RNA-seq based T cell inflamed GEP was associated with ORR in both ccRCC and nccRCC but associated with PFS. There was limited power in this study given the sample size constraints.  Further analysis of IHC, DNA, and RNA has been planned.

Presented by: David F. McDermott, MD, Professor, Medicine, Harvard Medical School, Staff Physician, Hematology/Oncology, Beth Israel Deaconess Medical Center, Director, Biologic Therapy and Cutaneous Oncology Programs, Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA

Written by: Jason Zhu, MD. Medical Oncologist, Division of Genitourinary Cancers, Levine Cancer Institute Twitter: @TheRealJasonZhu at the 2020 ASCO Annual Meeting, Virtual Scientific Program #ASCO20, May 29-31, 2020.

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Clinical Trial Information: NCT02853344