LBA40 Neoadjuvant nivolumab and nivolumab plus ipilimumab induce (near-) complete responses in patients with head and neck squamous cell carcinoma: The IMCISION trial

Zuur, L.; Vos, Joris L.; Elbers, Joris B. W.; Krijgsman, Oscar; Qiao, Xiaohang; Leun, Anne M. van der; Smit, Laura A.; Brekel, Michiel W. van den; Tan, Brandon; Jasperse, Bas; Vogel, Wouter V.; Willems, Stefan M.; Peeper, Daniel S.; Blank, Christian U.; Boer, Jan Paul de; Haanen, John B.A.G.

doi:10.1016/j.annonc.2020.08.2270

Cited by 15 publications

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“…Moreover, the changes in hypoxia could also suggest a potential synergy with nivolumab, as changes in intratumoral hypoxia following anti-PD-1 therapy have been shown to be predictive of PTR in the IMCISION study. 34 Overall, these findings are also in line with the results of the FAZA-PET imaging in patients S-001 (cPR) and S-002 (mPR), which showed a significant reduction in hypoxia within the tumor area pre-surgery.…”

Section: Discussionsupporting

confidence: 86%

“… 33 Recurrence rates in the pembrolizumab and nivolumab plus/minus ipilimumab studies were lower than expected to historical controls for this disease, and preliminary data from the IMCISION phase II study by Zuur et al showed a strong correlation between PTR and both disease-free and overall survival. 34 In the SNOW study, all patients were alive and with no recurrence after almost 2 years follow-up. These results are encouraging considering that over half of the patients had stage IVA, especially when recurrence rates in this group of patients can be as high as 50% in the first year.…”

Section: Discussionmentioning

confidence: 94%

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Antitumor immune effects of preoperative sitravatinib and nivolumab in oral cavity cancer: SNOW window-of-opportunity study

Oliva

Chepeha

Araújo

et al. 2021

J Immunother Cancer

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BackgroundSitravatinib, a tyrosine kinase inhibitor that targets TYRO3, AXL, MERTK and the VEGF receptor family, is predicted to increase the M1 to M2-polarized tumor-associated macrophages ratio in the tumor microenvironment and have synergistic antitumor activity in combination with anti-programmed death-1/ligand-1 agents. SNOW is a window-of-opportunity study designed to evaluate the immune and molecular effects of preoperative sitravatinib and nivolumab in patients with oral cavity squamous cell carcinoma.MethodsPatients with newly-diagnosed untreated T2-4a, N0-2 or T1 >1 cm-N2 oral cavity carcinomas were eligible. All patients received sitravatinib 120 mg daily from day 1 up to 48 hours pre-surgery and one dose of nivolumab 240 mg on day 15. Surgery was planned between day 23 and 30. Standard of care adjuvant radiotherapy was given based on clinical stage. Tumor photographs, fresh tumor biopsies and blood samples were collected at baseline, at day 15 after sitravatinib alone, and at surgery after sitravatinib–nivolumab combination. Tumor flow cytometry, multiplex immunofluorescence staining and single-cell RNA sequencing (scRNAseq) were performed on tumor biopsies to study changes in immune-cell populations. Tumor whole-exome sequencing and circulating tumor DNA and cell-free DNA were evaluated at each time point.ResultsTen patients were included. Grade 3 toxicity occurred in one patient (hypertension); one patient required sitravatinib dose reduction, and one patient required discontinuation and surgery delay due to G2 thrombocytopenia. Nine patients had clinical-to-pathological downstaging, with one complete response. Independent pathological treatment response (PTR) assessment confirmed a complete PTR and two major PTRs. With a median follow-up of 21 months, all patients are alive with no recurrence. Circulating tumor DNA and cell-free DNA dynamics correlated with clinical and pathological response and distinguished two patient groups with different tumor biological behavior after sitravatinib alone (1A) versus sitravatinib–nivolumab (1B). Tumor immunophenotyping and scRNAseq analyses revealed differential changes in the expression of immune cell populations and sitravatinib-targeted and hypoxia-related genes in group 1A vs 1B patients.ConclusionsThe SNOW study shows sitravatinib plus nivolumab is safe and leads to deep clinical and pathological responses in oral cavity carcinomas. Multi-omic biomarker analyses dissect the differential molecular effects of sitravatinib versus the sitravatinib–nivolumab and revealed patients with distinct tumor biology behavior.Trial registration numberNCT03575598.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 94%

Antitumor immune effects of preoperative sitravatinib and nivolumab in oral cavity cancer: SNOW window-of-opportunity study

Oliva

Chepeha

Araújo

et al. 2021

J Immunother Cancer

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“…However, TCE can be bypassed by various immunotherapy strategies [ 58 , 59 , 60 , 61 , 62 , 63 ]. Currently, immune checkpoint inhibitors are investigated in the neoadjuvant setting in OCSCC, and this could allegedly enhance CD8 + T-cell activity and reverse tumor host interplay, thus reducing also the risk of tumor escape at distant sites [ 64 , 65 , 66 , 67 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

Metavariables Resuming Host Immune Features and Nodal Involvement Are Associated with Oncological Outcomes in Oral Cavity Squamous Cell Carcinoma

Missale

Bugatti

Mattavelli

et al. 2021

Cells

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Oral cavity squamous cell carcinoma (OSCC) is a common head and neck cancer characterized by a poor prognosis associated with locoregional or distant failure. Among the predictors of prognosis, a dense infiltration of adaptive immune cells is protective and associated with improved clinical outcomes. However, few tools are available to integrate immune contexture variables into clinical settings. By using digital microscopy analysis of a large retrospective OSCC cohort (n = 182), we explored the clinical significance of tumor-infiltrating CD8+ T-cells. To this end, CD8+ T-cells counts were combined with well-established clinical variables and peripheral blood immune cell parameters. Through variable clustering, five metavariables (MV) were obtained and included descriptors of nodal (NODALMV) and primary tumor (TUMORMV) involvement, the frequency of myeloid (MYELOIDMV) or lymphoid (LYMPHOIDMV) peripheral blood immune cell populations, and the density of tumor-infiltrating CD8+ T-cells (TI-CD8MV). The clinical relevance of the MV was evaluated in the multivariable survival models. The NODALMV was significantly associated with all tested outcomes (p < 0.001), the LYMPHOIDMV showed a significant association with the overall, disease-specific and distant recurrence-free survival (p < 0.05) and the MYELOIDMV with the locoregional control only (p < 0.001). Finally, TI-CD8MV was associated with distant recurrence-free survival (p = 0.029). Notably, the performance in terms of survival prediction of the combined effect of NODALMV and immune metavariables (LYMPHOIDMV, MYELOIDMV and TI-CD8MV) was superior to the TNM stage for most of the outcomes analyzed. These findings indicate that the analysis of the baseline host immune features are promising tools to complement clinical features, in stratifying the risk of recurrences.

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“…[19 ▪ ], Zuur et al . [20 ▪ ] and Hanna et al . [21 ▪ ]), with a targeted therapeutic (Merlino et al .…”

Section: Introductionmentioning

confidence: 93%

Preoperative immunotherapy for head and neck cancers: state of art

Egloff

Uppaluri

2022

Current Opinion in Oncology

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Purpose of reviewProgrammed cell death 1 (PD-l)-targeting agents have been FDA-approved for treatment of recurrent/ metastatic head and neck squamous cell carcinoma (HNSCC). Clinical studies employing these agents preoperatively for HNSCC in the definitive setting are emerging and have important implications. Recent findingsPreclinical studies demonstrate enhanced effectiveness of preoperative PD-1 targeting compared with postoperative treatment. Nine HNSCC clinical studies evaluating preoperative treatment with PD-1-targeted pembrolizumab/nivolumab alone or in combination therapy were recently reported. These studies differed by preoperative treatment type and duration and reported no surgical delays, no unexpected surgical complications and grade 3--4 immune-related adverse events consistent with the employed immunotherapeutic agent(s). Rates of major pathologic response (MPR), reduced residual viable tumour to 10% or less, ranged from 2.9--31% across eight trials without neoadjuvant radiation therapy. Higher PD-1 ligand (PD-L1) expression, increased inflammatory gene expression and enhanced immune cell tumour infiltration in baseline biopsies were associated with pathologic tumour response (pTR) in some studies. Any degree of pTR was associated with improved survival/relapse outcomes in two studies.

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LBA40 Neoadjuvant nivolumab and nivolumab plus ipilimumab induce (near-) complete responses in patients with head and neck squamous cell carcinoma: The IMCISION trial

Cited by 15 publications

References 0 publications

Antitumor immune effects of preoperative sitravatinib and nivolumab in oral cavity cancer: SNOW window-of-opportunity study

Antitumor immune effects of preoperative sitravatinib and nivolumab in oral cavity cancer: SNOW window-of-opportunity study

Metavariables Resuming Host Immune Features and Nodal Involvement Are Associated with Oncological Outcomes in Oral Cavity Squamous Cell Carcinoma

Preoperative immunotherapy for head and neck cancers: state of art

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