Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial

Lee, Nancy Y.; Ferris, Robert L.; Psyrri, Amanda; Haddad, Robert I.; Tahara, Makoto; Bourhis, Jean; Harrington, Kevin; Chang, Peter Mu‐Hsin; Lin, Jin‐Ching; Razaq, Mohammad; Teixeira, Margarida; Lövey, József; Chamois, J.; Rueda, Antonio; Hu, Chaosu; Dunn, Lara; Dvorkin, Mikhail; Beukelaer, S. De; Pavlov, Dmitri; Thurm, Holger; Cohen, Ezra E.W.

doi:10.1016/s1470-2045(20)30737-3

Cited by 323 publications

(185 citation statements)

References 25 publications

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“…In recent years, patients suffered diverse types of cancer have had benefits from immune checkpoint inhibitors (ICIs) therapies, which were principally represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors [ 7 , 8 ]. Inspired by such good news, many clinical trials of ICIs were constructed in patients with advanced ESCC.…”

Section: Introductionmentioning

confidence: 99%

Post treatment NLR is a predictor of response to immune checkpoint inhibitor therapy in patients with esophageal squamous cell carcinoma

Han

Zhong

et al. 2021

Cancer Cell Int

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Background In view of the fact that peripheral blood parameters have been reported as predictors of immunotherapy to various cancers, this study aimed to determine the predictors of response to anti-programmed death-1 (anti-PD-1) therapy in patients with esophageal squamous cell carcinoma (ESCC) from peripheral blood parameters. Methods A retrospective analysis was conducted to investigate the predictive value of peripheral blood parameters including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) in the response to anti-PD-1 antibody treatment. 119 ESCC patients receiving combined treatment including anti-PD-1 antibody were enrolled in this study. Results The median progression-free survival (PFS) of all ESCC patients was 3.73 months. PFS rate in ESCC patients with low NLR at 6 weeks post treatment was higher than patients with high NLR (HR = 2.097, 95% CI 0.996–4.417, P = 0.027). However, PFS rate in ESCC patients with low NLR at baseline (HR = 1.060, 95% CI 0.524–2.146, P = 0.869) or 3 weeks post treatment (HR = 1.293, 95% CI 0.628–2.663, P = 0.459) was comparable with high NLR. And no statistically different was found in PFS rate between low PLR and high PLR at baseline (HR = 0.786, 95% CI 0.389–1.589, P = 0.469), 3 weeks post treatment (HR = 0.767, 95% CI 0.379–1.552, P = 0.452) or 6 weeks post treatment (HR = 1.272, 95% CI 0.624–2.594, P = 0.488) in ESCC patients. PFS rate was also comparable between low MLR and high MLR at baseline (HR = 0.826, 95% CI 0.408–1.670, P = 0.587), 3 weeks post treatment (HR = 1.209, 95% CI 0.590–2.475, P = 0.580) or 6 weeks post treatment (HR = 1.199, 95% CI 0.586–2.454, P = 0.596). PFS rate was similar between patients with low SII and high SII at baseline (HR = 1.120, 95% CI 0.554–2.264, P = 0.749), 3 weeks post treatment (HR = 1.022, 95% CI 0.500–2.089, P = 0.951) and 6 weeks post treatment (HR = 1.759, 95% CI 0.851–3.635, P = 0.097). Conclusions NLR at 6 weeks post treatment is a predictor of the response to anti-PD-1 treatment in patients with ESCC.

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Section: Introductionmentioning

confidence: 99%

Post treatment NLR is a predictor of response to immune checkpoint inhibitor therapy in patients with esophageal squamous cell carcinoma

Han

Zhong

et al. 2021

Cancer Cell Int

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“…In a Canadian and European multi-center trial (NCT03410615), standard cisplatin-chemoradiation is currently compared with durvalumab-based radioimmunotherapy for locoregionally advanced intermediate-risk HPV-positive OSCC, whereby the radioimmunotherapy group is further randomized between durvalumab or durvalumab/tremelimumab maintenance. While the JAVELIN head-and-neck 100 Phase III trial failed to show a benefit of adding avelumab to definitive chemoradiation for locally advanced HNSCC [ 45 ], it will be interesting to see the safety and efficacy of checkpoint inhibitor-based radioimmunotherapy in these de-escalation studies for HPV-related OSCCs.…”

Section: De-escalation Strategies For Hpv-positive Oropharyngeal Cancersmentioning

confidence: 99%

De-Escalation Strategies of (Chemo)Radiation for Head-and-Neck Squamous Cell Cancers—HPV and Beyond

Rühle

Grosu

Nicolay

2021

Cancers

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Oncological outcomes for head-and-neck squamous cell carcinoma (HNSCC) patients are still unsatisfactory, especially for advanced tumor stages. Besides the moderate survival rates, the prevalence of severe treatment-induced normal tissue toxicities is high after multimodal cancer treatments, both causing significant morbidity and decreasing quality of life of surviving patients. Therefore, risk-adapted and individualized treatment approaches are urgently needed for HNSCC patients to optimize the therapeutic gain. It has been a well-known fact that especially HPV-positive oropharyngeal squamous cell carcinoma (OSCC) patients exhibit an excellent prognosis and may therefore be subject to overtreatment, resulting in long-term treatment-related toxicities. Regarding the superior prognosis of HPV-positive OSCC patients, treatment de-escalation strategies are currently investigated in several clinical trials, and HPV-positive OSCC may potentially serve as a model for treatment de-escalation also for other types of HNSCC. We performed a literature search for both published and ongoing clinical trials and critically discussed the presented concepts and results. Radiotherapy dose or volume reduction, omission or modification of concomitant chemotherapy, and usage of induction chemotherapy are common treatment de-escalation strategies that are pursued in clinical trials for biologically selected subgroups of HNSCC patients. While promising data have been reported from various Phase II trials, evidence from Phase III de-escalation trials is either lacking or has failed to demonstrate comparable outcomes for de-escalated treatments. Therefore, further data and a refinement of biological HNSCC stratification are required before deescalated radiation treatments can be recommended outside of clinical trials.

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“…While the results of the PACIFIC and CheckMate-577 studies demonstrate the potential utility of immunotherapy to improve the outcomes of patients treated with radiotherapy for locally advanced malignancies, other attempts to combine radiotherapy and immunotherapy in the definitive setting have been less successful in demonstrating consistent benefits. The JAVELIN Head and Neck 100 and PembroRad trials both represent unsuccessful attempts to improve the outcomes of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) with the addition of concurrent immune checkpoint blockade (ICB) agents to definitive radiotherapy [15,16]. Similarly, the results of CheckMate-498 and Checkmate-548, which investigated the addition of concurrent nivolumab to radiotherapy in patients with O6-methylguanine-DNA methyltransferase (MGMT)-unmethylated glioblastoma multiforme (GBM) and temozolomide and radiotherapy in patients with MGMT-methylated GBM, respectively, failed to demonstrate the efficacy of nivolumab in these settings [17][18][19][20][21].…”

Section: Addition Of Immunotherapy To Definitive Local Therapymentioning

confidence: 99%

“…Accordingly, studies using murine models treated with concurrent ICB and radiotherapy have demonstrated that the addition of the draining lymph nodes to the radiotherapy treatment volume results inferior OS [28]. Thus, it is conceivable that large elective nodal volumes contributed to the failure of studies investigating concurrent ICB and radiotherapy for locally advanced HNSCC [15,16].…”

Section: Addition Of Immunotherapy To Definitive Local Therapymentioning

confidence: 99%

Treatment of Cancer with Radio-Immunotherapy: What We Currently Know and What the Future May Hold

Turchan

Pitroda

Weichselbaum

2021

IJMS

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Radiotherapy and immunotherapy are most effective as cancer therapies in the setting of low-volume disease. Although initial studies of radio-immunotherapy in patients with metastatic cancer have not confirmed the efficacy of this approach, the role of radio-immunotherapy in patients with limited metastatic burden is unclear. We propose that further investigation of radio-immunotherapy in metastatic patients should focus upon patients with oligometastatic disease.

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Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial

Cited by 323 publications

References 25 publications

Post treatment NLR is a predictor of response to immune checkpoint inhibitor therapy in patients with esophageal squamous cell carcinoma

Post treatment NLR is a predictor of response to immune checkpoint inhibitor therapy in patients with esophageal squamous cell carcinoma

De-Escalation Strategies of (Chemo)Radiation for Head-and-Neck Squamous Cell Cancers—HPV and Beyond

Treatment of Cancer with Radio-Immunotherapy: What We Currently Know and What the Future May Hold

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