Discordant Responses Between Primary Head and Neck Tumors and Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation of Radiographic and Pathologic Treatment Effect.

PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect. Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent change in tumor volume from pretreatment to posttreatment CT scan. Responders were defined as those with a 10% reduction in the volume of the primary tumor or lymph nodes (LN). Pathologic treatment effect (PTE) was defined as the area showing fibrosis or lymphohistiocytic inflammation divided by total tumor area. Sixteen of 32 patients (50%) with pathologic evidence of LN involvement exhibited discordant PTE between primary sites and LN. In four patients with widely discordant adjacent LN, increased PTE was associated with increased infiltration of tumor CD8 Nivolumab often induces discordant treatment effects between primary tumor sites and metastatic lymph nodes within subjects. This treatment discordance was also demonstrated in adjacent lymph nodes, which may correlate with local immune cell makeup. Finally, although these data were generated by a relatively small population size, our data support the use of early radiographic response to assess immunotherapy treatment effect in HNSCC.

Informations de copyright

Copyright © 2020 Merlino, Johnson, Tuluc, Gargano, Stapp, Harshyne, Leiby, Flanders, Zinner, Axelrod, Curry, Cognetti, Mannion, Kim, Rodeck, Argiris and Luginbuhl.

Déclaration de conflit d'intérêts

UR serves on Scientific Advisory Board of Akrevia/Xilio. YK serves on the Scientific Advisory Board for the following companies: Aduro, Sanofi, Takeda, Mersanna, and Dracen. Additionally, Bristol Myers Squibb contributed funding to this study, but did not participate in data collection, analysis, or patient recruitment. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.