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Poster Display session 3

5559 - Transcriptome signatures of treatment responses in a preoperative window of opportunity trial of nivolumab and tadalafil in resectable squamous cell carcinoma of the head and neck

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Tumour Site

Head and Neck Cancers

Presenters

Sanket Shukla

Citation

Annals of Oncology (2019) 30 (suppl_5): v449-v474. 10.1093/annonc/mdz252

Authors

S. Shukla1, J.M. Johnson2, J.M. Curry3, Y. Kim4, A. Argiris2, A. Luginbuhl5, L. Harshyne2, U. Rodeck1

Author affiliations

  • 1 Dermatology And Cutaneous Biology, Thomas Jefferson University, 19107 - Philadelphia/US
  • 2 Medical Oncology, Thomas Jefferson University, 19107 - Philadelphia/US
  • 3 Department Of Otolaryngology–head & Neck Surgery, Thomas Jefferson University, 19107 - Philadelphia/US
  • 4 Dept Of Otolaryngology Head And Neck Surgery, Vanderbilt University, 37232 - Nashville/US
  • 5 Otolaryngology, Thomas Jefferson University, 19107 - Philadelphia/US

Resources

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Abstract 5559

Background

Immunotherapy with nivolumab, an anti-PD-1 blocking antibody, is clinically approved for the management of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) but it benefits only a minority of patients. The phosphodiesterase (PDE) 5 inhibitor tadalafil was found to lower intratumoral myeloid-derived suppressor cells and regulatory T cells in SCCHN patients. Here we describe exploratory analyses of immune-related gene expression correlates of nivolumab with or without concurrent administration of tadalafil administered for 4 weeks before planned surgical resection in the context of a completed randomized, window-of-opportunity trial.

Methods

RNA-seq was performed on pre- and post-treatment tumor tissues from 28 patients receiving either nivolumab alone (n = 12) or nivolumab and tadalafil (n = 16). RNA was sequenced (NextSeq 500) using 75bp paired-end chemistry at a depth of ∼50 million reads.

Results

Consistent with previous work, pretreatment biopsies of HPV(+) SCCHN (n = 19) were more strongly immune infiltrated when compared to HPV(-) (n = 9) cancers. Preliminary principal component analysis of pretreatment gene expression suggests that select transcripts related to T cells and inflammation were predicitve of clinical outcomes in HPV(+) SCCHN. Nivolumab treatment enhanced expression of a broad range of immune-related genes in both HPV(+) and HPV(-) SCCHNs and this signature was amplified by tadalafil. Whereas transcript patterns consistent with enhanced myeloid cell infiltration after treatment were observed in both, HPV(+) and HPV(-) HNSCCs, T cell gene expression signatures were more pronounced in HPV(+) cancers.

Conclusions

These results point to diverse intratumoral immune states triggered by nivolumab/tadalafil in HPV(+) when compared to HPV(-) SCCHNs. They challenge the notion that increased presence of intratumoral T lymphocytes alone is associated with favorable therapeutic responses to PD1 inhibition in SCCHN. Yet, select pretreatment transcripts associated with innate and/or adaptive immune responses may have prognostic relevance.

Clinical trial identification

NCT 03238365.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Bristol-Myers Squibb.

Disclosure

All authors have declared no conflicts of interest.

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