Checkpoint inhibitors: Better outcomes among advanced cutaneous head and neck melanoma patients

Hirshoren, Nir; Yoeli, Roni; Cohen, Jonathan; Weinberger, Jeffrey M.; Caplan, Nadia; Merims, Sharon; Peretz, Tamar; Lotem, Michal

doi:10.1371/journal.pone.0231038

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…The findings of this study underscore a significant improvement in the survival of this patient population, with the median survival increasing from a historical 10 months to over 40 months in the present day 20 . This is further corroborated by Hirshoren et al, who also reported superior results of IT in advanced H&N melanoma compared to cutaneous melanoma of limbs and trunk (mOS of 60.2, 51.2, and 53.4, respectively) 21 …”

Section: Discussionsupporting

confidence: 84%

“…20 This is further corroborated by Hirshoren et al, who also reported superior results of IT in advanced H&N melanoma compared to cutaneous melanoma of limbs and trunk (mOS of 60.2, 51.2, and 53.4, respectively). 21 Recent pivotal trials have shown that combination IT has a numerical advantage in mOS over anti-PD-1 monotherapy, although the difference was not statistically significant. 5 In our study cohort, only a small portion of BRAF positive patients were treated with TT in the first line setting.…”

Section: Discussionmentioning

confidence: 99%

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Real‐World Outcomes of Inoperable and Metastatic Cutaneous Head and Neck Melanoma Patients

Rozendorn,

Shutan,

Feinmesser

et al. 2024

The Laryngoscope

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ObjectiveThis study aims to describe the overall survival (OS) and to identify associated prognostic factors in patients with inoperable and metastatic cutaneous melanoma of the head and neck (H&N) region, undergoing modern systemic treatments.MethodsThis is a retrospective single institutional study. Data on all consecutive H&N melanoma patients treated with systemic oncologic treatments between 2015 and 2022 were collected from electronic medical files. Kaplan–Meier curves were used to describe survival and Cox regression analysis was used to identify patient and tumor factors associated with prognosis.ResultsA total of 144 patients were included. Median OS was 45 months (95% confidence interval [CI] 28–65 m). On univariable analysis for OS, the primary disease site, specifically the nape and neck (hazard ratio [HR] 3.3, 95% CI 1.4–7.7, p = 0.007), high Eastern Cooperative Oncology Group Performance Status ([ECOG‐PS], HR 2.5, 95% CI = 1.9–3.3, p < 0.001), high lactate dehydrogenase (LDH) levels (HR 2.8, 95% CI = 1.7–4.6, p < 0.001), and treatment with targeted therapy (TT) as compared with immunotherapy (HR 2.6, 95% CI = 1.06–6.3, p = 0.03) were all associated with shorter OS. High‐grade adverse events (AEs) were associated with a longer OS (HR 0.41, 95% CI = 0.25–0.68, p = 0.001). On multivariable analysis for OS, the ECOG‐PS, LDH levels, site of disease, and the development of moderate‐severe AEs remained significant.ConclusionsIn the era of modern oncologic treatments, the prognosis of inoperable and metastatic cutaneous H&N melanoma aligns with other cutaneous melanomas. Primary tumor site of the nape and neck region emerges as a significant prognostic factor.Level of Evidence3 Laryngoscope, 2024

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Real‐World Outcomes of Inoperable and Metastatic Cutaneous Head and Neck Melanoma Patients

Rozendorn,

Shutan,

Feinmesser

et al. 2024

The Laryngoscope

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“…Drugs such as ipilimumab are designed to target CTLA-4 and enhance anti-tumor immunity by removing this block to T-cell activation ( Soldevilla et al, 2019 ). Clinical trials have demonstrated the efficacy of CTLA-4 inhibitors in the treatment of cancers, including melanoma ( Hirshoren et al, 2020 ).…”

Section: Advantages and Limitations Of Gene Therapy In The Context Of...mentioning

confidence: 99%

Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update

Moaveni,

Amiri,

Shademan

et al. 2024

Front. Mol. Biosci.

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Pediatric cancers represent a tragic but also promising area for gene therapy. Although conventional treatments have improved survival rates, there is still a need for targeted and less toxic interventions. This article critically analyzes recent advances in gene therapy for pediatric malignancies and discusses the challenges that remain. We explore the innovative vectors and delivery systems that have emerged, such as adeno-associated viruses and non-viral platforms, which show promise in addressing the unique pathophysiology of pediatric tumors. Specifically, we examine the field of chimeric antigen receptor (CAR) T-cell therapies and their adaptation for solid tumors, which historically have been more challenging to treat than hematologic malignancies. We also discuss the genetic and epigenetic complexities inherent to pediatric cancers, such as tumor heterogeneity and the dynamic tumor microenvironment, which pose significant hurdles for gene therapy. Ethical considerations specific to pediatric populations, including consent and long-term follow-up, are also analyzed. Additionally, we scrutinize the translation of research from preclinical models that often fail to mimic pediatric cancer biology to the regulatory landscapes that can either support or hinder innovation. In summary, this article provides an up-to-date overview of gene therapy in pediatric oncology, highlighting both the rapid scientific progress and the substantial obstacles that need to be addressed. Through this lens, we propose a roadmap for future research that prioritizes the safety, efficacy, and complex ethical considerations involved in treating pediatric patients. Our ultimate goal is to move from incremental advancements to transformative therapies.

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“…The first antibodies that progressed into clinical trials after showing promising results in cancer treatment were ipilimumab, tremelimumab and quavonlimab, three anti-CTLA-4 antibodies. Ipilimumab is clinically employed for treatment of unresectable stage III/IV metastatic melanoma and as adjuvant therapy for radically resected "high-risk" melanoma patients [ 46 , 47 , 48 , 49 ], while tremelimumab and quavonlimab are currently being tested in clinical trials for safety and efficacy determination.…”

Section: Immune Checkpoint Blocker Delivery With Nanocarriersmentioning

confidence: 99%

Advanced Nanotechnology for Enhancing Immune Checkpoint Blockade Therapy

et al. 2021

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Immune checkpoint receptor signaling pathways constitute a prominent class of “immune synapse,” a cell-to-cell connection that represses T-lymphocyte effector functions. As a possible evolutionary countermeasure against autoimmunity, this strategy is aimed at lowering potential injury to uninfected cells in infected tissues and at minimizing systemic inflammation. Nevertheless, tumors can make use of these strategies to escape immune recognition, and consequently, such mechanisms represent chances for immunotherapy intervention. Recent years have witnessed the advance of pharmaceutical nanotechnology, or nanomedicine, as a possible strategy to ameliorate immunotherapy technical weaknesses thanks to its intrinsic biophysical properties and multifunctional modifying capability. To improve the long-lasting response rate of checkpoint blockade therapy, nanotechnology has been employed at first for the delivery of single checkpoint inhibitors. Further, while therapy via single immune checkpoint blockade determines resistance and a restricted period of response, strong interest has been raised to efficiently deliver immunomodulators targeting different inhibitory pathways or both inhibitory and costimulatory pathways. In this review, the partially explored promise in implementation of nanotechnology to improve the success of immune checkpoint therapy and solve the limitations of single immune checkpoint inhibitors is debated. We first present the fundamental elements of the immune checkpoint pathways and then outline recent promising results of immune checkpoint blockade therapy in combination with nanotechnology delivery systems.

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Checkpoint inhibitors: Better outcomes among advanced cutaneous head and neck melanoma patients

Cited by 6 publications

References 30 publications

Real‐World Outcomes of Inoperable and Metastatic Cutaneous Head and Neck Melanoma Patients

Real‐World Outcomes of Inoperable and Metastatic Cutaneous Head and Neck Melanoma Patients

Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update

Advanced Nanotechnology for Enhancing Immune Checkpoint Blockade Therapy

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