A combined genomic and immune profile in patients with head and neck squamous cell carcinoma treated with immunotherapy: A pilot study.

Medientyp: E-Artikel

Titel: A combined genomic and immune profile in patients with head and neck squamous cell carcinoma treated with immunotherapy: A pilot study

Beteiligte: Botticelli, Andrea; Mezi, Silvia; Pomati, Giulia; Zizzari, Ilaria; Cerbelli, Bruna; Mammone, Giulia; Corsi, Alessandro; di Gioia, Cira; D'Amati, Giulia; della Rocca, Carlo; Catalano, Carlo; De Vincentiis, Marco; Polimeni, Antonella; Valentini, Valentino; Tombolini, Vincenzo; Nuti, Marianna; Marchetti, Paolo

Erschienen: American Society of Clinical Oncology (ASCO), 2020

Sprache: Englisch

DOI: 10.1200/jco.2020.38.15_suppl.e18506

ISSN: 0732-183X; 1527-7755

Schlagwörter: Cancer Research ; Oncology

Entstehung:

Anmerkungen:

Beschreibung: e18506 Background: In head and neck squamous cell carcinoma (HNSCC) only a small subset of patients (pts) really benefits from immunotherapy, suggesting the need of validated molecular and immunological predictive biomarkers. The aim of the study was to evaluate both the genomic and immune profile of HNSCC correlating it to early progression to immunotherapy. Methods: This is a pilot study evaluating immune and molecular profile in platinum-refractory HNSCC pts treated with Nivolumab. Blood samples were collected at baseline (T0) and at second cycle of therapy (T1). The immune profile was studied by multiplex assay, evaluating circulating: CD137, CTLA4, PD1, PDL1, PDL2, CD27, TIM3, LAG3, GITR, HVEM, BTLA, CD80, CD28 and IDO. The comprehensive genomic profile was evaluated at baseline on formalin-fixed paraffin-embedded samples of the tumor through Foundation One Cdx test. The results obtained were correlated with early progression (within 3 months from the start of therapy). Results: Ten pts were enrolled in the study. Early progression occurred in 6 pts (60%). Median progression free survival and overall survival were 3 months (1-11) and 6.5 months (1-12), respectively. In all patients ≥ 5 genetic mutations were detected; median number of mutation was 6 (5-14); 8/10 pts had a tumor mutational burden less than 10 Muts/mb. The more frequent genetic alterations involved the cycline-dependent-kynase pathway (9/10), the transcription factor associated gene TP53 (8/10) and the PI3K-Akt-PTEN signaling pathways (5/10). Less frequent alterations involved FGFR family (4/10), NOTCH signaling pathway (3/10) and TERT (4/10). Early progression was slightly associated with the number of mutations detected (p = 0.06). The rising or falling trend of circulating levels of biomarkers were detected in 9/10 pts and included modification in IDO (1/10), LAG3 (3/10), GITR (3/10), BTLA (3/10), CD137 (4/10), CTLA4 (4/10), PD1 (2/10), Tim3 (3/10), CD28 (3/10), HVEM (3/10), CD80 (2/10). No modifications were recorded in PDL1, PDL2 and CD27. Conclusions: Our results, although in a small cohort, highlighted the complexity and heterogeneity of landscape in HNSCC pts. A novel evaluation that combines molecular and immune profile is needed. In the context of a poor prognosis disease the combination of personalized molecular and immune approaches could represent a promising strategy to improve survival.

Zugangsstatus: Freier Zugang

Nur in Feld suchen:

Zuletzt gesuchte Begriffe: