Immunotherapy Advances in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Its Relationship With Human Papillomavirus

Wang, Huanhuan; Zhao, Qin; Zhang, Yuyu; Zhang, Qihe; Zheng, Zhuangzhuang; Liu, Shiyu; Liu, Zijing; Meng, Lingbin; Xin, Ying; Jiang, Xin

doi:10.3389/fimmu.2021.652054

Cited by 26 publications

(28 citation statements)

References 92 publications

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“… 16 Whereas single clinical trials found a better outcome of HPV positive tumors during immune checkpoint inhibition, a recent meta-analysis was negative. 44 45 In the CheckRad-CD8 trial these patients had an excellent prognosis with a 2-year PFS rate of 94% in the RIT cohort. However, it has to be considered that these patients also have a very good prognosis on platinum-based radiochemotherapy as demonstrated in the RTOG 1016 trial.…”

Section: Discussionmentioning

confidence: 98%

Induction chemoimmunotherapy followed by CD8+ immune cell-based patient selection for chemotherapy-free radioimmunotherapy in locally advanced head and neck cancer

Hecht

Eckstein

Rutzner

et al. 2022

J Immunother Cancer

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PurposeThe first aim of the trial is to study feasibility of combined programmed death protein ligand 1/cytotoxic T-lymphocyte-associated protein 4 inhibition concomitant to radiotherapy. In addition, efficacy of the entire treatment scheme consisting of induction chemoimmunotherapy followed by chemotherapy-free radioimmunotherapy (RIT) after intratumoral CD8 +immune cell-based patient selection will be analyzed.MethodsPatients with stage III–IVB head and neck squamous cell carcinoma were eligible for this multicenter phase II trial. Treatment consisted of a single cycle of cisplatin 30 mg/m² days 1–3, docetaxel 75 mg/m² day 1, durvalumab 1500 mg fix dose day 5 and tremelimumab 75 mg fix dose day 5. Patients with increased intratumoral CD8 +immune cell density or pathological complete response (pCR) in the rebiopsy entered RIT up to a total dose of 70 Gy. Patients received further three cycles of durvalumab/tremelimumab followed by eight cycles of durvalumab mono (every 4 weeks). The intended treatment for patients not meeting these criteria was standard radiochemotherapy outside the trial. Primary endpoint was a feasibility rate of patients entering RIT to receive treatment until at least cycle 6 of immunotherapy of ≥80%.ResultsBetween September 2018 and May 2020, 80 patients were enrolled (one excluded). Out of these, 23 patients had human papilloma virus (HPV)-positive oropharyngeal cancer. Median follow-up was 17.2 months. After induction chemoimmunotherapy 41 patients had pCR and 31 had increased intratumoral CD8 +immune cells. Of 60 patients entering RIT (primary endpoint cohort), 10 experienced imiting toxic (mainly hepatitis) and four discontinued for other reasons, resulting in a feasibility rate of 82%. The RIT cohort (n=60) had a progression-free survival (PFS) rate at one and 2 years of 78% and 72%, respectively, and an overall survival rate at one and 2 years of 90% and 84%, respectively. Patients with HPV-positive oropharyngeal cancers had greater benefit from RIT with a 2-year PFS rate of 94% compared with 64% for HPV-negative oropharyngeal cancers and other locations. In the entire study cohort (n=79) the 2-year PFS rate was 68% (91% for HPV-positive oropharynx vs 59% for others). Toxicity grade 3–4 mainly consisted of dysphagia (53%), leukopenia (52%) and infections (32%).ConclusionsThe trial met the primary endpoint feasibility of RIT. Induction chemo-immunotherapy followed by chemotherapy-free RIT after intratumoral CD8 +immune cell-based patient selection has promising PFS.Trial registration numberThe trial was registered with ClinicalTrials.gov (identifier: NCT03426657). The trial was conducted as investigator-sponsored trial (IST).

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Section: Discussionmentioning

confidence: 98%

Induction chemoimmunotherapy followed by CD8+ immune cell-based patient selection for chemotherapy-free radioimmunotherapy in locally advanced head and neck cancer

Hecht

Eckstein

Rutzner

et al. 2022

J Immunother Cancer

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“…Treatment of recurrent and/or metastatic OPSCC is similar to that of other recurrent and/or metastatic HNSCC. There is no specific recommendation for oropharyngeal tumors and no particularities according to the HPV status [8,44,90]. However, even with a metastatic disease, HPV-positive OPSCC patients still harbor a better prognosis than HPV-negative OPSCC patients [90,91].…”

Section: Recurrent And/or Metastatic Opsccmentioning

confidence: 99%

Current Therapeutic Strategies in Patients with Oropharyngeal Squamous Cell Carcinoma: Impact of the Tumor HPV Status

Bozec

Culié

Poissonnet

et al. 2021

Cancers

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Since there is no published randomized study comparing surgical and non-surgical therapeutic strategies in patients with oropharyngeal squamous cell carcinoma (OPSCC), the therapeutic management of these patients remains highly controversial. While human papillomavirus (HPV)-positive and HPV-negative OPSCC are now recognized as two distinct diseases with different epidemiological, biological, and clinical characteristics, the impact of HPV status on the management of OPSCC patients is still unclear. In this review, we analyze the current therapeutic options in patients with OPSCC, highlighting the most recent advances in surgical and non-surgical therapies, and we discuss the impact of HPV status on the therapeutic strategy.

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“…ICIs are the blocking antibodies against inhibitory immune checkpoints (ICs) targeting the specific mechanisms that tumor cells employ to evade immune system detection [ 8 ]. Despite the promising results of ICIs therapy in melanoma [ 9 , 10 ], urothelial carcinoma [ 11 ], lung tumors [ 12 , 13 ], colorectal tumors [ 14 ], and head and neck squamous cell carcinoma [ 15 ], clinical gains are far from universal. In some of the major tumor types (e.g., breast and pancreas), the clinical efficacy of ICIs remains very limited [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Diets on Response to Immune Checkpoint Inhibitors (ICIs) Therapy against Tumors

Zhang

et al. 2022

Life

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Immunotherapy has revolutionized the established therapeutics against tumors. As the major immunotherapy approach, immune checkpoint inhibitors (ICIs) achieved remarkable success in the treatment of malignancies. However, the clinical gains are far from universal and durable, because of the primary and secondary resistance of tumors to the therapy, or side effects induced by ICIs. There is an urgent need to find safe combinatorial strategies that enhance the response of ICIs for tumor treatment. Diets have an excellent safety profile and have been shown to play pleiotropic roles in tumor prevention, growth, invasion, and metastasis. Accumulating evidence suggests that dietary regimens bolster not only the tolerability but also the efficacy of tumor immunotherapy. In this review, we discussed the mechanisms by which tumor cells evade immune surveillance, focusing on describing the intrinsic and extrinsic mechanisms of resistance to ICIs. We also summarized the impacts of different diets and/or nutrients on the response to ICIs therapy. Combinatory treatments of ICIs therapy with optimized diet regimens own great potential to enhance the efficacy and durable response of ICIs against tumors, which should be routinely considered in clinical settings.

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Immunotherapy Advances in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Its Relationship With Human Papillomavirus

Cited by 26 publications

References 92 publications

Induction chemoimmunotherapy followed by CD8+ immune cell-based patient selection for chemotherapy-free radioimmunotherapy in locally advanced head and neck cancer

Induction chemoimmunotherapy followed by CD8+ immune cell-based patient selection for chemotherapy-free radioimmunotherapy in locally advanced head and neck cancer

Current Therapeutic Strategies in Patients with Oropharyngeal Squamous Cell Carcinoma: Impact of the Tumor HPV Status

Impact of Diets on Response to Immune Checkpoint Inhibitors (ICIs) Therapy against Tumors

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