Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study

Long, Georgina V.; Atkinson, Victoria; Lo, Serigne; Sandhu, Shahneen; Guminski, Alexander; Brown, Michael P.; Wilmott, James S.; Edwards, Jarem; Gonzalez, Maria; Scolyer, Richard A.; Menzies, Alexander M.; McArthur, Grant A.

doi:10.1016/s1470-2045(18)30139-6

Cited by 800 publications

(724 citation statements)

References 17 publications

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“…The electronic search identified 1350 articles, 1278 of which did not meet the eligibility criteria; the remaining 72 articles were examined in detail. [16][17][18]20,21,[27][28][29][30][31][32][33][34][35][36] The 15 studies provided 26 cohorts for the analysis and 1132 patients. An additional 59 studies subsequently were excluded (see Supporting Table 2): 14 clinical trials did not report informative results for the analyses, 33 were not prospective clinical studies, 2 studies were a duplicate publication of an article that already was included, 1 was a preclinical study, 4 publications were reviews or correspondences, and 5 studies investigated treatments not eligible for the current analysis.…”

Section: Discussionmentioning

confidence: 99%

The impact of targeted therapies and immunotherapy in melanoma brain metastases: A systematic review and meta‐analysis

Rulli

Legramandi

Salvati

et al. 2019

Cancer

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BACKGROUND: Targeted therapies (TT), combination immunotherapy (CMI), and monoimmunotherapy (MI) in combination with radiotherapy (CRI) or not are commonly used in patients with melanoma brain metastases, but studies that directly compare these strategies are lacking. The current meta-analysis aimed to better elucidate their activity and efficacy. METHODS: A systematic search of MEDLINE, Embase, and conference proceedings up to January 2019 was performed to identify trials investigating combination TT, monotargeted TT (mono TT), MI, CMI, and CRI in melanoma brain metastases. The outcomes considered were progression-free survival (PFS), overall survival (OS), and the objective response rate (ORR) as evaluated at both intracranial and extracranial sites. Random effects models were used to compare the different therapeutic strategies. RESULTS: A total of 15 trials were included that provided 1132 patients for analyses. CMI demonstrated a statistically significant better OS compared with MI (P = .03, P = .05, and P = .03, respectively, at 6 months, 18 months, and 24 months) and combination TT (P = .04 and P = .03, respectively, at 18 months and 24 months). CMI demonstrated a statistically significant better PFS compared with combination TT (P < .001 at 12 months and 18 months), MI (P = .02, P < .02, and P = .05, respectively, at 6 months, 12 months, and 18 months), and mono TT (P < .001 at 6 months, 12 months, and 18 months). The intracranial objective response rate was higher with CMI compared with mono TT (P < .001) and MI (P < .001), whereas there was no difference between CMI and combination TT. CONCLUSIONS: The results of the current metaanalysis suggested that CMI increases long-term PFS and OS compared with MI and combination TT. Combination TT and CMI are associated with a similar intracranial response rate. The role of systemic therapy in combination with radiotherapy remains to be better elucidated. Cancer 2019;125:3776-3789.

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Section: Discussionmentioning

confidence: 99%

The impact of targeted therapies and immunotherapy in melanoma brain metastases: A systematic review and meta‐analysis

Rulli

Legramandi

Salvati

et al. 2019

Cancer

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“…10,11 For patients with multifocal disease, median overall survival (OS) is significantly shorter at 6 months. 14,15 The same combination therapy provides comparable beneficial effects in patients with melanoma brain metastases, 16,17 yet ICI therapy has had little beneficial clinical impact in glioblastoma patients. There is no standard management for recurrent glioblastoma.…”

Section: Standard Treatment and Prognosismentioning

confidence: 99%

Clinical chimeric antigen receptor‐T cell therapy: a new and promising treatment modality for glioblastoma

2019

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Chimeric antigen receptor (CAR)‐T cell therapy is now approved in the United States and Europe as a standard treatment for relapsed/refractory B‐cell malignancies. It has also been approved recently by the Therapeutic Goods Administration in Australia and may soon be publicly reimbursed. This advance has accentuated scientific, clinical and commercial interest in adapting this exciting technology for the treatment of solid cancers where it is widely recognised that the challenges of overcoming a hostile tumor microenvironment are most acute. Indeed, CAR‐T cell technology may be of the greatest value for those cancers that lack pre‐existing immunity because they are immunologically ‘cold’, or have a low somatic tumor mutation load, or both. These cancers are generally not amenable to therapeutic immune checkpoint blockade, but CAR‐T cell therapy may be effective because it provides an abundant supply of autologous tumor‐specific T cells. This is achieved by using genetic engineering to re‐direct autologous T‐cell cytotoxicity towards a tumor‐associated antigen, bypassing endogenous T‐cell requirements for antigen processing, MHC‐dependent antigen presentation and co‐stimulation. One of the most challenging solid cancers is glioblastoma, which has among the least permissive immunological milieu of any cancer, and which is almost always fatal. Here, we argue that CAR‐T cell technology may counter some glioblastoma defences and provide a beachhead for furthering our eventual therapeutic aims of restoring effective antitumor immunity. Although clinical investigation of CAR‐T cell therapy for glioblastoma is at an early stage, we discuss three recently published studies, which feature significant differences in target antigen, CAR‐T cell phenotype, route of administration and tumor response. We discuss the lessons, which may be learned from these studies and which may guide further progress in the field.

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“…Under certain conditions, tumor cells appear to be tolerant to or even dependent on the immune system. [69][70][71][72] However, the simultaneous use of anti-CTLA-4 and anti-PD-1 in combination with PTT accelerates the death of tumor-bearing mice 46 possibly because combined therapy with anti-CTLA-4 and anti-PD-1 is likely to trigger treatmentrelated adverse events of grade 3 or 4. These mechanisms are also involved in photothermal immunotherapy and are the main obstacles against its application and development.…”

Section: Photothermal Immunotherapy Combined With Immune Checkpoint Bmentioning

confidence: 99%

Nanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment

Hou

Tao

Pang

et al. 2018

Intl Journal of Cancer

186

123

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Nanoparticle-based phototherapies, such as photothermal therapy (PTT) and photodynamic therapy (PDT), exhibit strong efficacy, minimal invasion and negligible side effects in tumor treatment. These phototherapies have received considerable attention and been extensively studied in recent years. In addition to directly killing tumor cells through heat and reactive oxygen species, PTT and PDT can also induce various antitumor effects. In particular, the resultant massive tumor cell death after PTT and PDT triggers immune responses, including the redistribution and activation of immune effector cells, the expression and secretion of cytokines and the transformation of memory T lymphocytes. The antitumor effects can be enhanced by immune checkpoint blockage therapy. This article reviewed the recent advances of nanoparticle-based PTT and PDT, summarized the studies on nanoparticle-based photothermal and photodynamic immunotherapies in vitro and in vivo, and discussed challenges and future research directions.

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Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study

Cited by 800 publications

References 17 publications

The impact of targeted therapies and immunotherapy in melanoma brain metastases: A systematic review and meta‐analysis

The impact of targeted therapies and immunotherapy in melanoma brain metastases: A systematic review and meta‐analysis

Clinical chimeric antigen receptor‐T cell therapy: a new and promising treatment modality for glioblastoma

Nanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment

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