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.
Resources from the same session
5389 - Two-weekly accelerated BEP (aBEP) regimen as induction chemotherapy (CT) in intermediate and poor prognosis patients (pts) with nonseminomatous germ cell tumors (NSGCT): final results of phase II trial.
Presenter: Alexey Tryakin
Session: Poster Display session 3
Resources:
Abstract
2934 - Differential expression of circulating miR375 and miR371 to detect teratoma and viable germ cell malignancy
Presenter: Lucia Nappi
Session: Poster Display session 3
Resources:
Abstract
3585 - Prognosis of anaemia in disseminated testicular germ cell tumours. On behalf of the Spanish Germ Cell Cancer Group (SGCCG)
Presenter: Esmeralda Garcia Torralba
Session: Poster Display session 3
Resources:
Abstract
2254 - The Effects Of Primary Testicular Tumor Localization On Prognosis In Patients With Nonseminomatous Testis Cancer
Presenter: Birol Yildiz
Session: Poster Display session 3
Resources:
Abstract
4505 - Initial Results of a Phase II study of Nivolumab and Ipilimumab in Metastatic Adrenal Tumors.
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
3369 - NEMIO: a randomized phase II trial evaluating efficacy and safety of dose dense MVAC (ddMVAC) + durvalumab +/- tremelimumab as neoadjuvant treatment in patients with bladder muscle-invasive urothelial carcinoma
Presenter: Constance Thibault
Session: Poster Display session 3
Resources:
Abstract
2075 - KEYNOTE-866: Phase 3 Study of Perioperative Pembrolizumab (pembro) or Placebo (pbo) in Combination With Neoadjuvant Chemotherapy in Cisplatin (cis)-Eligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
4824 - KEYNOTE-905: A Phase 3 Study of Cystectomy Plus Perioperative Pembrolizumab Versus Cystectomy Alone in Cisplatin (cis)-Ineligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Matthew Galsky
Session: Poster Display session 3
Resources:
Abstract
2253 - Phase 3 LEAP-011 trial: First-Line Pembrolizumab With Lenvatinib in Patients With Advanced Urothelial Carcinoma Ineligible to Receive Platinum-Based Chemotherapy
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
4310 - PULSE : A Single Arm Trial Assessing The Activity and Safety of Avelumab Immunotherapy Maintenance among Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma (mSCPC).
Presenter: Noemie Gassian
Session: Poster Display session 3
Resources:
Abstract