Systemic Therapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma- A Systematic Review and Meta-Analysis

Lau, Ashley; Yang, Wei‐En; Li, Kar-Yan; Su, Yu‐xiong

doi:10.1016/j.critrevonc.2020.102984

Cited by 42 publications

(30 citation statements)

References 60 publications

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“…The gender effect on the response to immunotherapy was widely investigated in several studies, such as the different susceptibility of autoimmune disease according to the reproductive status. Despite the controversial results of durvalumab alone or in combination with tremelimumab in Eagle and Condor studies, two recent metanalysis demonstrated the benefit of anti-PD-L1based therapy, in terms of survival and safety, in recurrent disease, suggesting a specific role in this setting that could be immunologically different from the metastatic ones (40,41). Furthermore, durvalumab demonstrated higher efficacy, in terms of response rate and survival, in HPV-positive patients (42), highlighting the putative role of HPV infection in the modulation of immune response creating a more "ready to act" microenvironment (43,44).…”

Section: Discussionmentioning

confidence: 99%

Anti–PD-1 and Anti–PD-L1 in Head and Neck Cancer: A Network Meta-Analysis

et al. 2021

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ObjectiveThe monoclonal antibodies anti-programmed death protein-1 (anti–PD-1) nivolumab and pembrolizumab are the first immune checkpoint inhibitors (ICIs) approved for treatment of recurrent/metastatic head and neck carcinoma R/M HNSCC in first line and in platinum refractory disease. This network meta-analysis aims to investigate the efficacy of anti–PD-1- vs anti–PD-L1-based therapy in R/M HNSCC cancer patients through a systematic review of the literature to provide support for evidence-based treatment decisions. In particular, the effectiveness of ICIs for R/M HNSCC is analyzed according to the different mechanisms of action of the check-points inhibitory drugs in different subgroups of patients.MethodsWe did a systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs) in PubMed, ClinicalTrials.gov, Embase, Medline, the Cochrane Central Register of Controlled Trials, Web of Science. Our search identified a total of five randomized controlled trials: Keynote 040, Keynote 048, Eagle, Condor, Checkmate 141. These trials included 3001 patients. Treatment was sub-categorized into PD-L1–based, PD-1–based, and standard chemotherapy. Treatments were indirectly compared with anti–PD-L1-based therapy.ResultsThe network meta-analysis demonstrated no significant differences in OS between different subgroups except for the metastatic patients in which anti–PD-1-based therapy was associated with significantly less risk of death. Furthermore, anti–PD-1-based therapy appeared to be effective in smoker patients and in human papilloma–negative (HPV) patients. Conversely, anti–PD-L1-based therapy seems to be better efficient in female patients, in locally recurrent setting and in HPV positive patients.ConclusionThis is the first NMA study that aimed to indirectly compare anti–PD-1- and anti–PD-L1-based therapy in HNSCC patients. The results of our NMA could help define a profile of patient responder or resistant to specific classes of immune drugs and can be used to guide/design future studies in the novel scenario of precision immune-oncology.

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Section: Discussionmentioning

confidence: 99%

Anti–PD-1 and Anti–PD-L1 in Head and Neck Cancer: A Network Meta-Analysis

et al. 2021

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“…Combination of Cisplatin and 5Fluorouracil has represented the preferred regimen for several years, yielding an overall survival (OS) of about 9 months in clinical trials. As alternative, in patients unfit for the polychemotherapy, single agent cisplatin or methotrexate were extensively used in the clinical practice, nevertheless obtaining a significantly lower OS [ 64 , 65 , 66 , 67 ].…”

Section: The Role Of Systemic Strategies (Chemo and Immunotherapy)mentioning

confidence: 99%

Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: A Big and Intriguing Challenge Which May Be Resolved by Integrated Treatments Combining Locoregional and Systemic Therapies

Ionna¹,

Bossi

Guida³

et al. 2021

Cancers

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Squamous cell carcinoma of the head and neck (SCCHN) is a complex group of malignancies, posing several challenges to treating physicians. Most patients are diagnosed with a locally advanced disease and treated with strategies integrating surgery, chemotherapy, and radiotherapy. About 50% of these patients will experience a recurrence of disease. Recurrent/metastatic SCCHN have poor prognosis with a median survival of about 12 months despite treatments. In the last years, the strategy to manage recurrent/metastatic SCCHN has profoundly evolved. Salvage treatments (surgery or re-irradiation) are commonly employed in patients suffering from locoregional recurrences and their role has gained more and more importance in the last years. Re-irradiation, using some particularly fractionating schedules, has the dual task of reducing the tumor mass and eliciting an immune response against cancer (abscopal effect). In this review, we will analyze the main systemic and/or locoregional strategies aimed at facing the recurrent/metastatic disease, underlining the enormous importance of the multidisciplinary approach in these types of patients.

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“…Despite the vast number of completed and ongoing studies aiming to target EGFR and other downstream signaling pathways, cetuximab remains the only FDA approved EGFR targeted mAb for the treatment of SCCHN. Prior to the introduction of molecularly targeted agents, first line treatment for RM SCCHN was largely comprised of several cytotoxic agents that were associated with significant morbidity [ 62 ]. Eventually, cisplatin was studied in SCCHN and was found to have a favorable response rate (RR) compared to best supportive care (BSC) and methotrexate.…”

Section: Role Of Egfr Inhibition In Recurrent Metastatic Disease In Scchnmentioning

confidence: 99%

Current Aspects and Future Considerations of EGFR Inhibition in Locally Advanced and Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck

Patel

Saba

2021

Cancers

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Recurrent metastatic (RM) and locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) are devasting disease states with limited therapeutic options and poor overall survival. Targeting the epidermal growth factor receptor (EGFR) is one area that has helped improve outcomes in this disease. Anti-EGFR based therapies have been shown to improve overall survival and mitigate the significant toxicities incurred from standard radiation, chemotherapy, and/or surgical options. Cetuximab, the most well-studied anti-EGFR monoclonal antibody, has demonstrated a positive impact on outcomes for RM and LA SCCHN. However, the development of early resistance to cetuximab highlights the need for a wider arsenal of therapy for RM and LA diseases. The use of immune checkpoint inhibitors has recently transformed the treatment of recurrent SCCHN. Drugs such as pembrolizumab and nivolumab have demonstrated success in recent clinical trials and have been approved for the treatment of advanced disease. Given the positive results of both EGFR targeted agents and immune checkpoint inhibitors, ongoing trials are studying their synergistic effects.

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Systemic Therapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma- A Systematic Review and Meta-Analysis

Cited by 42 publications

References 60 publications

Anti–PD-1 and Anti–PD-L1 in Head and Neck Cancer: A Network Meta-Analysis

Anti–PD-1 and Anti–PD-L1 in Head and Neck Cancer: A Network Meta-Analysis

Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: A Big and Intriguing Challenge Which May Be Resolved by Integrated Treatments Combining Locoregional and Systemic Therapies

Current Aspects and Future Considerations of EGFR Inhibition in Locally Advanced and Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck

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