HPV circulating tumor DNA to monitor response to pembrolizumab and vorinostat combination in patients with advanced HPV-related squamous-cell carcinomas

TL;DR

This study shows that HPV circulating tumor DNA levels can predict treatment response in patients with advanced HPV-related cancers.

Contribution

The study demonstrates the pharmacodynamic value of HPV-ctDNA as a biomarker for monitoring treatment outcomes in HPV-related squamous cell carcinomas.

Findings

HPV-ctDNA was detected in all patients with HPV-related SCC before treatment.

Higher pretreatment HPV-ctDNA levels were observed in anal cancer and metastatic disease.

Increasing HPV-ctDNA levels during treatment were associated with poorer outcomes.

Abstract

Limited data are available on the role of human papillomavirus circulating tumor DNA (HPV-ctDNA) as a pharmacodynamic marker to monitor the response to treatment in the recurrent/metastatic (R/M) setting. Our study aimed to investigate the sensitivity and pharmacodynamic value of HPV-ctDNA levels during treatment in patients with R/M HPV-related squamous cell carcinoma (SCC) treated with pembrolizumab in combination with vorinostat (PEVO trial, NCT04357873).

Plasma samples were prospectively collected from 57 patients with HPV-related SCC before treatment initiation and every 6 weeks until disease progression. HPV-ctDNA was quantified by droplet digital PCR. The levels before treatment were analyzed according to the patient and tumor characteristics. Landmark analyses were carried out to study the association between dynamic changes in HPV-ctDNA and progression-free survival (PFS), overall survival (OS), and overall response rate (ORR).

HPV-ctDNA was detected before treatment in all patients (n = 57) with HPV-related SCC. HPV-ctDNA levels correlated with the number of HPV copies in tumor tissue (P < 0.001). Higher levels of HPV-ctDNA in plasma samples were observed in anal cancer than in other tumor types (P < 0.001), and in patients with distant metastases with or without locoregional recurrence than in patients with locoregional recurrence alone (P = 0.02). The increase in HPV-ctDNA levels during treatment was associated with a lower ORR (P = 0.01) and shorter PFS and OS (both P = 0.01).

These findings reveal that dynamic HPV-ctDNA variation levels during treatment have a pharmacodynamic value and may help monitor treatment response in patients with advanced HPV-related SCC from different locations.

•HPV-ctDNA was detected in all patients with HPV-related SCC before treatment.•HPV-ctDNA levels correlated with HPV copy number in the tumor tissue.•Pretreatment higher HPV-ctDNA levels were observed in anal cancer and metastatic disease.•Increasing HPV-ctDNA levels during treatment were associated with poorer outcomes.

HPV-ctDNA was detected in all patients with HPV-related SCC before treatment.

HPV-ctDNA levels correlated with HPV copy number in the tumor tissue.

Pretreatment higher HPV-ctDNA levels were observed in anal cancer and metastatic disease.

Increasing HPV-ctDNA levels during treatment were associated with poorer outcomes.

Figures