Nivolumab vs investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression

Ferris, Robert L.; Blumenschein, George R.; Fayette, Jérôme; Guigay, J.; Colevas, A. Dimitrios; Licitra, Lisa; Harrington, Kevin; Kasper, Stefan; Vokes, Everett E.; Even, Caroline; Worden, Francis P.; Saba, Nabil F.; Docampo, Lara Carmen Iglesias; Haddad, Robert I.; Rordorf, Tamara; Kiyota, Naomi; Tahara, Makoto; Lynch, Mark; Jayaprakash, Vijayvel; Li, Li; Gillison, Maura L.

doi:10.1016/j.oraloncology.2018.04.008

Cited by 649 publications

(573 citation statements)

References 12 publications

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“…Importantly, infiltration of PD1 + T‐cells into HPV‐positive tumors was associated with favorable prognosis . More recently clinical trials have shown that immune checkpoint blockade significantly improves survival over standard therapy in recurrent HNSCC, including HPV‐OPC . These insights suggest that surrogates of a diminished immune response to tumor, such as TIL depletion, may predict poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Tumor‐infiltrating lymphocyte quantification stratifies early‐stage human papillomavirus oropharynx cancer prognosis

et al. 2019

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Objectives/Hypothesis To evaluate if a simple method for assessing tumor‐infiltrating lymphocytes (TIL) in primary tumor specimens improves the prognostic value of the American Joint Committee on Cancer, 8th Edition (AJCC8) cancer staging system in human papillomavirus–positive oropharyngeal squamous cell carcinoma (HPV‐OPC). Study Design Retrospective study. Methods In this study, TIL density was quantified on hematoxylin and eosin (H&E)–stained specimens from patients presenting to Johns Hopkins Hospital between 2009 and 2017 who underwent primary surgical therapy and had primary tumor specimens available for analysis. The prognostic effect of TIL density was evaluated by Kaplan‐Meier method and Cox proportional hazards models considering recurrence‐free survival (RFS) as the primary outcome. Results This study included 132 patients. Ninety‐five percent were classified by clinical criteria with AJCC8 early‐stage disease (stage I: 82%, stage II: 13%). After 84 months of follow‐up, 15 recurrences were observed. Among clinically early‐stage disease, TILhigh status was associated with improved RFS compared to TILlow (P = .002). Adjusted analysis showed TILhigh status was associated with 79% lower risk of recurrence than TILlow (adjusted hazard ratio [aHR]: 0.210, 95% confidence interval [CI]: 0.061‐0.723). In clinical stage I disease, TILhigh status was associated with improved RFS compared to TILlow in both univariate and multivariate analyses (hazard ratio: 0.235, P = .021; aHR: 0.218; 95% CI: 0.058‐0.822). TIL density similarly stratified risk in pathologically staged disease. Conclusions In patients with AJCC8 stage I disease, low TIL density was associated with diminished RFS. Our data suggest that assessing TIL density on H&E‐stained primary tumor specimens may enhance the prognostic resolution of the AJCC8 staging criteria for HPV‐OPC. Level of Evidence 4 Laryngoscope, 130:930–938, 2020

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Section: Discussionmentioning

confidence: 99%

Tumor‐infiltrating lymphocyte quantification stratifies early‐stage human papillomavirus oropharynx cancer prognosis

et al. 2019

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“…These percentages were then further divided into several categories: <1%, 1–4%, 5–24%, 25–49%, and ≥50%. As the threshold for PD‐L1 immunopositivity in SDCs has not yet been established, PD‐L1 immunopositivity was determined according to the criteria established in the KEYNOTE 012, Checkmate 141 and MEDI4736 trials for HNSCC . These criteria are: (i) a combined positive score (CPS) (calculated as the sum of positive TCs and positive ICs divided by the total TCs multiplied by 100) of at least 1; (ii) ≥1% of TCs stained; and (iii) ≥25% of TCs stained .…”

Section: Methodsmentioning

confidence: 99%

“…The use of checkpoint inhibitors in the management of patients with head and neck squamous cell carcinoma (HNSCC) has become increasingly common following successful early clinical trials. Additionally, it has been shown that blockade of programmed death‐1 (PD‐1) and/or programmed death ligand‐1 (PD‐L1) has positive therapeutic benefits in HNSCC patients . Moreover, PD‐1 and PD‐L1 have emerged as the key checkpoints that can be manipulated with inhibitory monoclonal antibodies.…”

Section: Introductionmentioning

confidence: 99%

The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

Jungbluth

Frosina

et al. 2019

Histopathology

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Aims Salivary duct carcinoma (SDC) is an aggressive salivary malignancy that results in high mortality rates and is often resistant to chemotherapy. Anti‐programmed death‐1 (PD‐1)/programmed death ligand‐1 (PD‐L1) checkpoint inhibitors have led to dramatic improvements in patients with various cancers. Other immunotherapeutic approaches, e.g. cancer vaccines, have shown promising results. Cancer testis antigens, e.g. preferentially expressed antigen in melanoma (PRAME), are regarded as promising vaccine targets because of their tumour‐specific expression pattern. Methods and results We analysed the immunoexpression of PD‐L1, PD‐1, major histocompatibility complex class I (MHC I) and PRAME in 53 SDCs. The immunoexpression levels of PD‐L1 in tumour cells (TCs) and immune cells (ICs), PD‐1 in ICs, PRAME in TCs and MHC I in TCs were analysed, and were correlated with outcome. PRAME expression was seen in 83% of SDCs. No PRAME staining was present in normal salivary gland tissue. With the three established diagnostic algorithms proposed for head and neck squamous cell carcinoma, the criteria being a combined positive score of ≥1, TC% ≥1%, and TC% ≥25%, 35 (66%), 17 (32%) and three cases (6%), respectively, were deemed to be positive for PD‐L1. PD‐1‐positive ICs were seen in 35 (66%) cases. MHC I down‐regulation was seen in 82% of SDCs. There was a significant correlation among PD‐L1 expression in ICs, PD‐1 expression in ICs, and PRAME expression in TCs. PD‐L1 expression in TCs and lack of PD‐1 expression in ICs were associated with decreased disease‐specific survival in SDC patients. Conclusions Alterations of the tumour immune microenvironment are common in SDCs, including expression of PD‐1/PD‐L1 and PRAME, which opens the way to potential novel immune therapies, such as cancer vaccination and PD‐1/PD‐L1 blockade, in these tumours.

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“…pembrolizumab and nivolumab) have been proved to be safe and effective [27,28,29]. Furthermore, the phase III randomized KEYNOTE-040 trial testing the efficacy of pembrolizumab versus standard treatment (methotrexate, docetaxel or cetuximab) is ongoing (ClinicalTrials.gov Identifier NCT02252042).…”

Section: Discussionmentioning

confidence: 99%

“…Modern agents (i.e. PD-1-receptor antibodies) have been proved to be safe and effective in patients with recurrent or metastatic SCCHN [27,28,29]. …”

Section: Introductionmentioning

confidence: 99%

Efficacy of Carboplatin/Paclitaxel-Based Radiochemotherapy in Locally Advanced Squamous Cell Carcinoma of Head and Neck

et al. 2018

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Background: Cisplatin-based chemotherapy (CTX) is commonly used concurrently with radiotherapy for head and neck cancer. The value of CTX regimens other than cisplatin for locally advanced squamous cell carcinoma of head and neck (LASCCHN) has not been well established. Here we compare the outcome of patients treated with different platinum-based chemotherapy regimens. Methods: Medical records from 104 patients with LASCCHN treated with radiochemotherapy (RCTX) between February 2013 and August 2016 were analyzed. Results: All patients were treated with intensity-modulated radiation therapy (51 definitive, 53 postoperative). The median total dose was 66.6 Gy and the median fraction dose was 1.8 Gy. 81 (78%) patients were administered cisplatin CTX, 23 (22%) patients received carboplatin and paclitaxel (CarboTaxol). The rate of recurrence was 38% in patients treated with cisplatin and 30% in CarboTaxol-treated patients (p = 0.6). Regarding the CTX regimens, event-free survival (EFS) was 37 versus 30 months (p = 0.6) and overall survival (OS) was 35 versus 28 months (p = 0.5) in cisplatin group versus CarboTaxol group, respectively. Significantly higher grade 3/4 acute toxicity in terms of dysphagia was observed following cisplatin-based RCTX (p = 0.002). In multivariable analysis, females and patients with early primary tumors (T1-2) have longer EFS and OS, regardless the CTX regimen. Conclusions: Primary or adjuvant RCXT with CarboTaxol is a safe and effective treatment alternative for LASCCHN patients with contraindication to cisplatin-based RCTX.

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Nivolumab vs investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression

Cited by 649 publications

References 12 publications

Tumor‐infiltrating lymphocyte quantification stratifies early‐stage human papillomavirus oropharynx cancer prognosis

Tumor‐infiltrating lymphocyte quantification stratifies early‐stage human papillomavirus oropharynx cancer prognosis

The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

Efficacy of Carboplatin/Paclitaxel-Based Radiochemotherapy in Locally Advanced Squamous Cell Carcinoma of Head and Neck

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