Is tebentafusp superior to combined immune checkpoint blockade and other systemic treatments in metastatic uveal melanoma? A comparative efficacy analysis with population adjustment

Petzold, Anne; Steeb, Theresa; Wessely, Anja; Koch, Elias A. T.; Vera, Julio; Berking, Carola; Heppt, Markus V.

doi:10.1016/j.ctrv.2023.102543

Cited by 18 publications

(13 citation statements)

References 15 publications

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“…Pradeep et al showed that the dual ICI regimen resulted in longer OS (hazard ratio = 0.65, 95% CI 0.53–0.79, P < 0.0001), longer PFS (hazard ratio = 0.48, 95% CI 0.38–0.60, P < 0.0001), and higher ORR (relative risk = 2.15, 95% CI 1.63–2.84, P < 0.001) for cutaneous melanoma. A recent review of systematic treatment for metastatic uveal melanoma by Petzold et al reported the median OS of anti-PD-1/PD-L1 antibodies (10.9 months, 95% confidence interval (CI): 9.8–13.4), anti-CTLA4 antibodies (7.8 months, 95% CI: 6.8–9.3), and dual-ICIs (15.7 months, 95% CI: 14.4–17.9), demonstrating a superior efficacy of dual-ICIs when compared with that with single ICIs, which is consistent with the results of the present study 62 . In addition, although limited to HLA-A*02:01-positive patients, this study demonstrated the longest median OS in tebentafusp (22.4 months, 95% CI: 19.9–29.6) 62 .…”

Section: Discussionsupporting

confidence: 91%

Immune checkpoint inhibitors for metastatic uveal melanoma: a meta-analysis

Yamada,

Takeuchi,

Fukumoto

et al. 2024

Sci Rep

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Several studies have evaluated immune checkpoint inhibitors (ICIs) for metastatic uveal melanoma; however, the efficacy of ICIs in the previous studies varied greatly. In this systematic review, we searched for prospective or retrospective studies on single or dual-ICIs for metastatic uveal melanoma treatment. A random-effect model meta-analysis with generic inverse-variance was conducted, and 36 articles representing 41 cohorts of 1414 patients with metastatic uveal melanoma were included. The pooled outcomes were as follows: objective response rate (ORR) was 5.6% (95% confidence interval [95%CI] 3.7–7.5%; I2, 36%), disease control rate (DCR) was 32.5% (95% CI 27.2–37.7%; I2, 73%), median progression-free survival was 2.8 months (95% CI 2.7–2.9 months; I2, 26%), and median overall survival (OS) was 11.2 months (95% CI 9.6–13.2 months; I2, 74%). Compared to single-agent ICI, dual ICI led to better ORR (single-agent: 3.4% [95% CI 1.8–5.1]; dual-agent: 12.4% [95% CI 8.0–16.9]; P < 0.001), DCR (single-agent: 29.3%, [95% CI 23.4–35.2]; dual-agent: 44.3% [95% CI 31.7–56.8]; P = 0.03), and OS (single-agent: 9.8 months [95% CI 8.0–12.2]; dual-agent: 16.3 months [95% CI 13.5–19.7]; P < 0.001). Our analysis provided treatment outcomes as described above. Dual-ICIs appear better than single-agent ICIs for the treatment of metastatic uveal melanoma.

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Section: Discussionsupporting

confidence: 91%

Immune checkpoint inhibitors for metastatic uveal melanoma: a meta-analysis

Yamada,

Takeuchi,

Fukumoto

et al. 2024

Sci Rep

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“…In the case of the data presented in graphs, the semi-automated extraction tool WebPlotDigitizer (https://automeris.io/WebPlotDigitizer/, Version 4.3) was utilized to extract data. 22,23…”

Section: Data Collection and Extractionmentioning

confidence: 99%

The efficacy and safety of oral microecological agents as add‐on therapy for atopic dermatitis: A systematic review and meta‐analysis of randomized clinical trials

Xue,

Qin,

Qin

et al. 2023

Clinical & Translational All

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BackgroundAtopic dermatitis (AD) is a common skin disease that is hard to completely cure in a short time. Guidelines recommend the use of topical corticosteroids (TCS) as first‐line anti‐inflammatory therapy for AD, but long‐term use has significant side effects. Microecological agents (MA), including probiotics, prebiotics and synbiotics, have been widely reported as a potential adjunctive therapy of AD, but whether MA can contribute to AD treatment is currently controversial. Therefore, we conducted a systematic review and meta‐analysis to investigate whether MA as an add‐on therapy for AD has synergistic and attenuated effects and to further understand the role of MA in clinical interventions for AD.MethodsWe systematically searched Medline, Embase, Web of Science, Cochrane Library and PsycINFO databases up to Apr 11, 2023, and bibliographies were also manually searched, for potentially relevant studies regarding MA as additional therapy of AD. The Cochrane Risk of Bias Tool for assessing risk of bias was used to assess the quality of randomized controlled trials (RCTs). Two reviewers screened studies, extracted data, and evaluated the risk of bias independently. The primary outcomes (SCORAD scores and the number of adverse events) and the secondary outcomes (pruritus scores, the quality of life and the frequency of TCS) were extracted from each article. The data were combined and analyzed to quantify the safety and efficacy of the treatment. R (V4.4.3) software was used for data synthesis. The certainty of the evidence was evaluated with the Grade of Recommendation, Assessment, Development and Evaluation (GRADE) system. We also performed a trial sequential analysis to assess the reliability of the evidence.ResultsA total of 21 studies, including 1230 individuals, were identified, 20 of which met the eligibility criteria for the meta‐analysis. Our pooled meta‐analyses showed that compared with controls, oral MA as an add‐on therapy was associated with significantly lower SCORAD scores (MD = −5.30, 95% CI −8.50, −1.55, p < 0.01, I2 = 81%). However, adverse events, pruritus scores, quality of life, and frequency of TCS use showed no significant difference in this meta‐analysis study (p > 0.05).ConclusionsThis meta‐analysis showed that MA plus TCS could be an effective and safe treatment for patients with AD to relieve relevant symptoms, which might be used as an add‐on therapy in the treatment of AD. However, due to the limited number of studies, results should be interpreted with caution. Further studies with a larger sample size are needed to explore the optimal protocol of MA plus TCS.

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“…The anti-PD1 agents nivolumab and pembrolizumab were also tested as monotherapies in phase II clinical trials. Both agents showed clinical responses that were sometimes durable; however, PFS and OS were highly variable and, overall, not so different from those obtained with chemotherapy[ 55 ]. Other two studies evaluated the combination of ipilimumab and nivolumab, after the very good results observed in cutaneous melanoma.…”

Section: Introductionmentioning

confidence: 99%

Uveal melanoma: Recent advances in immunotherapy

Sorrentino,

De Rosa,

Di Terlizzi

et al. 2024

World J Clin Oncol

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Uveal melanoma (UM) is the most common primary intraocular cancer in adults. The incidence in Europe and the United States is 6-7 per million population per year. Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection, up to 50% of UM patients develop metastases that usually involve the liver and are fatal within 1 year. To date, chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM, which is still characterized by poor prognosis. No standard therapeutic approaches for its prevention or treatment have been established. The application of immunotherapy agents, such as immune checkpoint inhibitors that are effective in cutaneous melanoma, has shown limited effects in the treatment of ocular disease. This is due to UM’s distinct genetics, natural history, and complex interaction with the immune system. Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations, UMs are usually triggered by a mutation in GNAQ or GNA11. As a result, more effective immunotherapeutic approaches, such as cancer vaccines, adoptive cell transfer, and other new molecules are currently being studied. In this review, we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.

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Is tebentafusp superior to combined immune checkpoint blockade and other systemic treatments in metastatic uveal melanoma? A comparative efficacy analysis with population adjustment

Cited by 18 publications

References 15 publications

Immune checkpoint inhibitors for metastatic uveal melanoma: a meta-analysis

Immune checkpoint inhibitors for metastatic uveal melanoma: a meta-analysis

The efficacy and safety of oral microecological agents as add‐on therapy for atopic dermatitis: A systematic review and meta‐analysis of randomized clinical trials

Uveal melanoma: Recent advances in immunotherapy

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