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Angiogenesis and T-cell inflamed gene expression profile (GEP) was associated with outcomes among patients with clear cell renal cell carcinoma (ccRCC), but not non-clear cell (ncc)RCC, according to results of a study presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
The study included 240 patients with advanced ccRCC and 45 patients with nccRCC who received targeted therapy as first-line treatment between 2006 and 2016. Tumor specimens were assessed for gene signatures and the PD-L2 gene. Multivariate analysis that adjusted for risk score, age, and other covariates was used to determine associations between gene signatures and PD-L2 expression and outcomes.
Worse prognosis, functional status, and more mTOR inhibitor use was associated with nccRCC compared with ccRCC.
Biomarker expression was higher among patients with ccRCC compared with nccRCC, including for vascular gene signature (P <.0001), T-cell inflamed GEP (P =.0009), granulocyte myeloid-derived suppressor cells (P =.0334), monocytic myeloid-derived suppressor cells (P <.0001), and PD-L2 expression (P =.0002).
Best overall response (BOR) was higher in the ccRCC group at 24% compared with 2.6% in the nccRCC group.
Among patients with ccRCC, both angiogenesis and T-cell inflamed GEP signatures were associated with outcomes. A higher angiogenesis gene score was associated with a higher BOR (31.0% vs 16.7%), longer progression-free survival (adjusted hazard ratio [aHR], 0.72; 95% CI, 0.55-0.95; P =.02), and trended toward improved overall survival (aHR, 0.76; 95% CI, 0.57-1.01; P =.06).
A higher T-cell inflamed GEP score was associated with higher BOR at 31.2% compared with 17.0% with a lower score (P =.01). A higher T-cell inflamed GEP was also associated with longer PFS (aHR, 0.64; 95% CI, 0.46-0.88), but OS was associated with a lower score (aHR, 0.84; 95% CI, 0.62-1.15; P =.27).
There were no biomarkers or gene signatures associated with outcomes among patients with nccRCC.
The authors concluded that “angiogenesis and T-cell inflamed GEP gene signatures were associated with response in ccRCC patients,” but also noted that these “results are hypothesis-generating and further exploration of correlates of response for nccRCC patients is warranted.”
Disclosures: Multiple authors declared affiliation with industry. Please refer to the original abstract for a full list of disclosures.
Read more of Cancer Therapy Advisor‘s coverage of the ESMO Virtual Congress 2020 by visiting the conference page.
Donskov F, Pinto CA, Predoui R, et al. Molecular profiles and response among metastatic renal cell carcinoma patients treated with targeted therapies. Presented at: European Society for Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract 155P.