96. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie

Prof. Dr.

Vorsitz

NUR Wissenschaftliches Programm / ONLY Scientific Programme

Medikamentöse Tumortherapie von Kopf-Hals-Tumoren – Zwischen Standardisierung und Personalisierung

Referat | Keynote lecture

Therapeutische Ansätze mit HPV Vakzinen bei HPV-assoziierten Oropharynxkarzinome

Vortrag auf Einladung

Neoadjuvante Ansätze: Erfolg durch Immuntherapie?

PhD, Assistant Prof.

MD, PhD

Aktuelle Entwicklungen in einer neoadjuvanten Phase-II-Studie mit Nivolumab allein oder in Kombination mit Relatlimab oder Ipilimumab bei resektablen Stadium III-IVA Kopf-Hals Plattenepithelkarzinomen (HNSCC)

Experimentelle Onkologie

ONKO-EXP

Introduction: Nivolumab (Nivo) monotherapy demonstrate modest efficacy in the treatment of metastatic HNSCC. Neoadjuvant trials incorporating Nivo may facilitate the development of more effective combination therapies in patients with surgically resectable HNSCC. This study evaluates the efficacy of combining Nivo with additional immune checkpoint inhibitors, specifically CTLA4 (ipilimumab, Ipi) and LAG3 (relatlimab, Rela).Material/Methods: This is a phase II randomized trial of neoadjuvant Nivo alone, or in combination with Ipi or Rela for 4 weeks prior to surgery. Response was evaluated using RECIST and standard pathologic response criteria. Pre- and post-treatment tumor samples were subjected to multispectral imaging and single cell RNA sequencing (scRNAseq) for T cell receptors and gene pathways analysis to identify biomarkers of response or progression.Results: Forty-two patients were enrolled with 37 available for analysis. No serious study drug-related AEs or unexpected surgical delays/complications were observed. RECIST response was not associated with pathologic response. Pathologic response rates were more frequent with Nivo/Rela (11/15, 73%) versus Nivo/Ipi (7/11, 64%) or Nivo (5/12, 42%) and correlated with favorable clinical outcomes. Spatial imaging revealed a Nivo/Ipi-specific influx of CD4+ helper T cells in the tumor and stroma, while scRNAseq of CD4+ T cells revealed ICR expression that correlates with pathologic response to Nivo/Rela. Discussion: Neoadjuvant combinations of Nivo/Ipi or Nivo/Rela were safe and linked to encouraging pathologic responses when compared to Nivo monotherapy. While the trial continues to enroll, a more comprehensive assessment of this strategy is necessary. Clinical trial information: NCT04080804.AcknowledgementsThis research was funded by BMS CA223049 (RLF), P50 CA097190 (RLF), R01 CA206517 (RLF), R01 DE031947 (RLF, LV, JHW), R01CA282074 (RLF and JHW) and DFG research fellowship #522169450 (MB). This research was supported in part by the University of Pittsburgh Center for Research Computing through the resources provided by using the HTC cluster, supported by NIH award number S10OD028483. This research utilized the UPMC Hillman Cancer Center Flow Cytometry Core Facility, supported in part by award P30 CA047904 (RLF).Ethics ApprovalThis study was approved by University of Pittsburgh"s Institutional Review Board; approval number HCC 18-139/CA224-056Declaration of Interests D.P.Z. declares competing interests with BICARA (steering committee), Seagen (steering committee), Inhibrx(consulting), Macrogenics (consulting), Prelude Therapeutics (advisory board), and Merck (advisory board) and research support (institutional) from Merck, BMS, AstraZeneca, GlaxoSmithKline, Aduro, Macrogenics, Bicara, and Novasenta. R.L.F. is cofounder and stockholder of Novasenta, and declares competing interests with Aduro Biotech, Inc. (consulting), AstraZeneca/MedImmune (clinical trial, research funding), Bristol-Myers Squibb (advisory board, clinical trial, research funding), EMD Serono (advisory board), MacroGenics Inc. (advisory board), Merck (advisory board, clinical trial), Novasenta (consulting, stock, research funding), Numab Therapeutics AG (advisory board), Pfizer (advisory board), Sanofi (consultant), Tesaro (research funding) and Zymeworks Inc. (consultant). T.C.B serves on the scientific advisory board of Walking Fish Therapeutics, BeSpoke Therapeutics, Mestag Therapeutics, Kalivir Therapeutics, and Galvanize Therapeutics. TCB is a consultant for Attivare Therapeutics and Tabby Therapeutics. L.V. is a co-inventor of a methodology licensed to INmune Bio, Inc. where DN-TNF can be used to prevent or treat malignancies. R.B. declares PCT/US15/612657 (Cancer Immunotherapy), PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof), PCT/US63/055227 (Methods and Compositions for Treating Autoimmune and Allergic Disorders); D.A.A.V. has patents covering LAG3, with others pending, and is entitled to a share in net income generated from licensing of these patent rights for commercial development. D.A.A.V: cofounder and stock holder – Novasenta, Potenza, Tizona, Trishula; stock holder – Oncorus, Werewolf; patents licensed and royalties - BMS, Novasenta; scientific advisory board member - Tizona, Werewolf, F-Star, Bicara, Apeximmune, T7/Imreg Bio; consultant - BMS, Incyte, Regeneron, Ono Pharma, Peptone, Avidity Partners; funding - BMS, Novasenta. A.R.C. is a consultant for AboundBio. The other authors declare no competing interests

Kopf-Hals-Onkologie

ONKO

Freier Vortrag

Dr. rer. nat.

Prof. Dr. med.

Dr. med.

PD Dr.

Verbessertes Langzeitüberleben und laryngektomiefreies Überleben nach Induktionschemotherapie mit Cetuximab bei Patienten mit fortgeschrittenem Larynx-/Hypopharynxkarzinom

Multimodal / Interdisziplinär

ONKO-IDZ

Introduction: Total laryngectomy (TL) is often the only surgical option guarantying resection of locally advanced laryngeal/hypopharyngeal squamous cell carcinoma (LA-LHSCC) with clear margins. Alternatively, chemo-radiotherapy (CRT) or induction chemotherapy (IC) with TP (docetaxel, cisplatin) or TPF (TP+5-FU) followed by radiotherapy (RT) may be used for larynx organ preservation (LOP). In cT4 LHSCC, TL followed by post-operative radio(chemo)therapy (POR(C)T) provides superior outcome compared to CRT. Residual disease or early recurrence after CRT demand salvage TL as the only remaining curative treatment option, often linked to fibrosis and impaired wound healing. These issues might be preventable by early response evaluation (ERE) after 1 cycle IC (IC-1). Material and Methods: DeLOS-II was a LOP trial utilizing ERE after IC-1 with TP(F) ± cetuximab (E) in patients with LA-LHSCC being only resectable via TL. Endoscopically estimated tumor surface shrinkage (ETSS) after IC-1 defined non-responders (<30%) with recommended TL+POR(C)T vs. responders (ETSS≥30%) receiving 2 further cycles TP(F)±E followed by RT. We assessed long-term outcome of 52 patients.Results: Within 125 months, 30 deaths (19/11 in arms A/B) occurred reflected by superior overall survival (OS) in arm B patients receiving E (p=0.023). Altogether, 35 (18/17) patients had LOP and 17 (9/8) received TL. All TL events occurred within 20 months. Receiving E or F did not influence LOP while E doubled the number of patients alive with larynx in place.Conclusion: The monocentric evaluation of 125-months data of LOP in DeLOS-II revealed feasibility of ERE regarding safety (all TL events occurred within 20 months) and significantly improved OS by adding E.Nein

Synergistische Effekte von Vitamin D und Anti-PD1-Antikörpern in der Immuntherapie von Kopf-Hals-Karzinomen – ein Ansatz zur Steigerung der Ansprechraten der Checkpoint-Inhibition

Klinische Studien / Immunonkologie

ONKO-KS/IMM

Einleitung: Anti-PD-1 Antikörper haben sich in der Therapie von rezidivierten und metastasierten Plattenepithelkarzinomen des Kopf-Hals-Bereichs (RM-HNSCC) etabliert, die Ansprechraten sind jedoch noch nicht zufriedenstellend. Die immunstimulierenden Effekte von Vitamin D im infektiologischen und onkologischen Kontext wurden in den zurückliegenden Jahren zunehmend besser verstanden, erste retrospektive Studien an nicht-HNSCC-Malignomen zeigen eine potentielle, synergistische Wirkung von Vitamin D und der Immuncheckpoint-Inhibition. Material und Methoden: In unsere retrospektive Studie wurden n=81 RM-HNSCC Patienten, bei denen eine Anti-PD1-Therapie durchgeführt und bei denen der 25-OH-Vitamin-D Serumspiegel vor, während und nach der Therapie bestimmt wurde, eingeschlossen. Das Ansprechen auf die Anti-PD-1 Therapie wurden mit dem Vitamin-D Spiegel der Patienten sowie weiteren klinischen Parametern korreliert.Ergebnisse: Patienten mit einer ausreichenden Vitamin D Versorgung zum Zeitpunkt des Beginns der Immuntherapie (25-OH-VitD ≥ 30ng/ml) zeigten ein signifikant besseres Ansprechen verglichen mit Patienten mit Vitamin D Mangel (25-OH-VitD <30ng/ml; ORR 78,6% vs. 14,9%; OR 20,9 [5,402-75,27]). Responder zeigten sowohl einen signifikant höheren Vitamin D Spiegel vor (p<0.0001) als auch einem höheren durchschnittlichen Vitamin-D Spiegel unter Therapie (p<0.0001). Diskussion: Eine ausreichende Vitamin D Versorgung scheint mit einem besseren Ansprechen auf eine Anti-PD-1-Immuntherapie einherzugehen. Die diesem Effekt zugrundeliegenden Mechanismen werden gegenwärtig in immuntherapeutischen in-vivo-Modellen untersucht, um basierend auf einem besseren Verständnis der molekularen Grundlagen eine erfolgreiche Translation in die klinisch-onkologische Praxis zu erreichen.Nein

Session 5 | Referatesitzung
Kopf-Hals-Tumore – Medikamentöse Tumortherapie

Termin

Vorsitz

Thema

Programm

Session 5 | ReferatesitzungKopf-Hals-Tumore – Medikamentöse Tumortherapie

Termin

Vorsitz

Thema

Programm

Session 5 | Referatesitzung
Kopf-Hals-Tumore – Medikamentöse Tumortherapie