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Gene-Expression Profiles and Response to Pembrolizumab in Advanced Squamous Cell Skin Cancer

By: Vanessa A. Carter, BS
Posted: Friday, May 3, 2024

Results from the KEYNOTE-629 trial demonstrated the efficacy of pembrolizumab monotherapy in patients with cutaneous squamous cell carcinoma, but it is unknown whether the 18-gene T-cell–inflamed gene-expression profile was associated with treatment response. Åse Bratland, PhD, of Oslo University Hospital, and colleagues performed a retrospective analysis on clinical data from these patients and found a correlation between gene-expression profile signatures and clinical outcomes in this population. Their findings were presented during the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract CT207/7).

“[The T-cell–inflamed gene-expression profile] was associated with tumor objective response to pembrolizumab but was not clearly associated with longer survival in patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma…,” the researchers mentioned. “While definitive conclusions require more analyses, these findings provide additional support for [this profile] as a predictive biomarker for cutaneous squamous cell carcinoma.”

Participants in KEYNOTE-629 received 200 mg of intravenous pembrolizumab every 3 weeks for up to 35 cycles. A total of 143 patients with locally advanced or recurrent or metastatic cutaneous squamous cell carcinoma had RNA-sequencing samples available for analysis.

The T-cell–inflamed gene-expression profile < first tertile and ≥ first tertile were identified in 33.6% and 66.4% of patients, respectively; median progression-free survival and overall survival were 4.1 vs 8.5 months and 25.1 vs 21.0 months. The gene-expression profile significantly correlated with an improved overall survival rate (P = .040) but not with progression-free survival or overall survival rates (P > .050). Furthermore, none of the 10 other consensus signatures were found to be associated with clinical outcomes. The area under the curve of the T-cell–inflamed gene-expression profile was relatively predictive of objective response rate, and Harrell’s C-index of the gene-expression profile was reasonably predictive of the duration of response and progression-free survival, according to the study authors.

Disclosure: For full disclosures of the study authors, visit abstractsonline.com.


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