32P - Tumor-agnostic plasma assay for circulating tumor DNA predicts outcome in recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with a PD-1 inhibitor

Background

Only 15-20% of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) patients derive long-term benefit from nivolumab or pembrolizumab. We developed a ctDNA tumor-agnostic assay aimed at the early prediction of single agent PD-1 inhibitor efficacy in R/M SCCHN.

Methods

Our tumor-agnostic assay included 37 genes frequently mutated in R/M SCCHN and two HPV16 genes. Primary endpoint was the concordance between ctDNA kinetics (ΔctDNA) and best overall response (BOR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1). ΔctDNA was defined as the difference in mean variant allele frequency (VAF) between the on-treatment sample harvested 6-10 weeks (FU1) after PD-1 inhibitor initiation and the pre-treatment plasma sample (ΔctDNA = mean FU1 VAF - mean pre-treatment VAF).

Results

ctDNA was detected in 35/44 (80%) of the pre-treatment plasma samples. The concordance between ΔctDNA and imaging response was observed in 74%. Median PFS was 8.6 months in the favorable ΔctDNA group and 2.5 months in the unfavorable ΔctDNA group (p=0.057). Median OS was 18.1 and 8.2 months in the favorable and unfavorable ΔctDNA groups, respectively (p=0.13). In patients with PD-L1 expressing SCCHN (Combined Positive Score ≥1), OS was significantly better in patients with favorable ΔctDNA compared with patients with unfavorable ΔctDNA: median OS was 8.4 and 41.5 months (p=0.033), respectively.

Conclusions

Tumor-agnostic ctDNA analysis for HPV-negative and HPV-positive R/M SCCHN is feasible. ctDNA kinetics show promising results in predicting the efficacy of PD-1 inhibitors in R/M SCCHN.

Clinical trial identification

NCT02139020.

Legal entity responsible for the study

The authors.

Funding

Foundation Saint-Luc.

Disclosure

C. Van Marcke de Lummen: Financial Interests, Institutional, Advisory Board: Eli Lilly, Novartis, AstraZeneca; Non-Financial Interests, Personal, Member of Board of Directors: BSMO. R. Galot: Other, Personal, Other, Travel expenses: Merck. J. Machiels: Financial Interests, Institutional, Advisory Board: Novartis, MSD, Pfizer, Roche, Debio, AstraZeneca, Innate, Nanobiotix, Bayer, Merck Serono, Boehringer Ingelheim, BMS, Pfizer, Cue Pharma, Incyte, Janssen, Johnson & Johnson, ALX Oncology, F-star, Nektar, F-star, Seagen, Astellas, Genmab; Financial Interests, Institutional, Other, Travel expense: Gilead, MSD, Sanofi; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, MSD; Financial Interests, Institutional, Coordinating PI: MSD, iTeos, eTheRNA; Financial Interests, Institutional, Local PI: Pfizer, Ceylad, MSD, Novartis, KURA, Roche, Lilly, Boehringer, Sanofi-Aventis, Incyte, Bayer, Merck Serono, Janssen, Johnson & Johnson, Amgen, AbbVie, GSK; Non-Financial Interests, Personal, Leadership Role, Chair: EORTC head and neck group. All other authors have declared no conflicts of interest.