Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study

Soulières, Denis; Tourneau, Christophe Le; Dinis, José; Licitra, Lisa; Ahn, Myung‐Ju; Soria, Ainara; Machiels, Jean‐Pascal; Mach, Nicolas; Mehra, Ranee; Zhang, Pingye; Cheng, Jonathan D.; Swaby, Ramona F.; Acosta-Rivera, Mirelis; Adkins, Douglas R.; Aghmesheh, Morteza; Airoldi, Mario; Aleknavičius, Eduardas; Al-Farhat, Yousuf; Algazi, Alain P.; Almokadem, Salah; Alyasova, Anna; Bauman, Jessica R.; Benasso, Marco; Berrocal, A.; Bray, Victoria; Burtness, Barbara; Caponigro, Francesco; Castro, Ana Tavares e; Cescon, Terrence P.; Chan, Kelvin; Chaudhry, Arvind; Chauffert, Bruno; Cohen, Ezra E.W.; Csőszi, Tibor; Boer, Jan Paul de; Delord, Jean‐Pierre; Dietz, Andreas; Dupuis, Charlotte; Digue, Laurence; Erfán, József; Álvarez, Yolanda; Evans, Mererid; Fidler, Mary J.; Förster, Martin; Friesland, Signe; Ganti, Apar Kishor; Geoffrois, Lionnel; Grant, Clíona; Gruenwald, Viktor; Harrington, Kevin J.; Hoffmann, Thomas; Horvai, Geza; Inčiūra, Arturas; Jang, Raymond; Jankowska, P.; Jimeno, Antonio; Joseph, Mano; Ramiro, Alejandro Juárez; Karaszewska, Bogusława; Kawecki, Andrzej; Keilholz, Ulrich; Keller, Ulrich; Kim, Sung‐Bae; Kocsis, Judit; Kotecki, Nuria; Kozloff, Mark; Lambea, J.; Littmann, László; Lantsukhay, Yuri; Lazarev, Sergey; Lee, Lip Way; Lifirenko, Igor; Martincic, Danko; Маторин, О. В.; McGrath, Margaret; Misiukiewicz, Krzysztof; Morris, John C.; Муфазалов, Ф. Ф.; Niu, Jiaxin; Srinivasan, Devraj; Segura, Pedro Pérez; Rauch, Daniel; Ribeiro, Maria Ângela Gonçalves de Oliveira; Rodriguez, Cristina P.; Rolland, Frédéric; Russo, Antonio; Ruzsa, Ágnes; Sanches, Frederico; Shin, Suji; Shtiveland, Mikhail; Specenier, Pol; Szekanecz, Éva; Judit, Szota; Herpen, Carla M.L. van; Velez-Cortes, Hector A.; Walsh, William; Wilop, Stefan; Winterhalder, Ralph; Wojtukiewicz, Marek Z.; Wong, Deborah Jean Lee; Zandberg, Dan P.

doi:10.1016/s0140-6736(18)31999-8

Cited by 1,277 publications

(1,093 citation statements)

References 24 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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“…31,32 With increasing follow-up and clinical data from a contemporary cohort, our model can be updated to reflect current practice changes and needs. First, the patients were not stratified into groups that shared similar characteristics.…”

Section: Discussionmentioning

confidence: 99%

Surveillance imaging for patients with head and neck cancer treated with definitive radiotherapy: A partially observed Markov decision process model

Ajayi

Schaefer

et al. 2019

Cancer

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BACKGROUND: A possible surveillance model for patients with head and neck cancer (HNC) who received definitive radiotherapy was created using a partially observed Markov decision process. The goal of this model is to guide surveillance imaging policies after definitive radiotherapy. METHODS: The partially observed Markov decision process model was formulated to determine the optimal times to scan patients. Transition probabilities were computed using a data set of 1508 patients with HNC who received definitive radiotherapy between the years 2000 and 2010. Kernel density estimation was used to smooth the sample distributions. The reward function was derived using cost estimates from the literature. Additional model parameters were estimated using either data from the literature or clinical expertise. RESULTS: When considering all forms of relapse, the model showed that the optimal time between scans was longer than the time intervals used in the institutional guidelines. The optimal policy dictates that there should be less time between surveillance scans immediately after treatment compared with years after treatment. Comparable results also held when only locoregional relapses were considered as relapse events in the model. Simulation results for the inclusive relapse cases showed that <15% of patients experienced a relapse over a simulated 36-month surveillance program. CONCLUSIONS: This model suggests that less frequent surveillance scan policies can maintain adequate information on relapse status for patients with HNC treated with radiotherapy. This model could potentially translate into a more cost-effective surveillance program for this group of patients. Cancer 2020;126:749-756.

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“…To determine PD‐L1 immunopositivity, the recommended cut‐off values are summarised in Table . These thresholds were established according to clinical response to the associated immune check‐point inhibitor in various clinical trials for UC,, HSCC and BC …”

Section: Methodsmentioning

confidence: 99%

Inter‐ and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma

et al. 2019

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Aims Programmed death‐ligand 1 (PD‐L1) expression by tumour cells (TC) is a mechanism for tumour immune escape through down‐regulation of antitumour T cell responses and is a target for immunotherapy. PD‐L1 status as a predictor of treatment response has led to the development of multiple biomarkers with different reference cut‐offs. We assessed pathologist consistency in evaluating PD‐L1 immunopositivity by examining the inter‐ and intraobserver agreement using various antibody clones and different cancer types. Methods and results PD‐L1 expression in TC and immune cells (IC) was manually scored in 27 head and neck squamous cell carcinoma (HSCC), 30 urothelial carcinoma (UC) and breast carcinoma (BC) using three commercial clones (SP263, SP142, 22C3) and one platform‐independent test (E1L3N). For interobserver agreement, PD‐L1 status was evaluated blindly by three pathologists. For intraobserver agreement, PD‐L1 expression was re‐evaluated following a wash‐out period. Intraclass correlation coefficient (ICC), overall percentage agreement (OPA) and κ‐values were calculated. Using clinical algorithms, the percentage of PD‐L1‐positive cases in HSCC, BC and UC were 15–81%, 47–67% and 7–43%, respectively. The percentage of PD‐L1 positive cases relied heavily on the algorithm/cut‐off values used. Almost perfect interobserver agreement was achieved using SP263 and E1L3N in HSCC, 22C3, SP142 and E1L3N in BC and 22C3 in UC. The SP142 clone in UC and HSCC showed moderate agreement and was associated with lower ICC and decreased intraobserver concordance. Conclusions Excellent inter‐ and intraobserver agreement can be achieved using SP263, 22C3 and E1L3N, whereas PD‐L1 scoring using SP142 clone is associated with a higher level of subjectivity.

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Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study

Cited by 1,277 publications

References 24 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

Surveillance imaging for patients with head and neck cancer treated with definitive radiotherapy: A partially observed Markov decision process model

Inter‐ and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma

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