Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma (KEYNOTE-716): distant metastasis-free survival results of a multicentre, double-blind, randomised, phase 3 trial

Long, Georgina V.; Luke, Jason J.; Khattak, Muhammad A.; Merino, Luis de la Cruz; Vecchio, Michele Del; Rutkowski, Piotr; Spagnolo, Francesco; Mackiewicz, Jacek; Chiarion-Sileni, Vanna; Kirkwood, John M.; Robert, Caroline; Grob, Jean‐Jacques; Galitiis, Federica De; Schadendorf, Dirk; Carlino, Matteo S.; Mohr, Peter; Dummer, Reinhard; Gershenwald, Jeffrey E.; Yoon, Charles H.; Wu, Xi; Fukunaga-Kalabis, Mizuho; Krepler, Clemens; Eggermont, Alexander; Ascierto, Paolo A.

doi:10.1016/s1470-2045(22)00559-9

Cited by 103 publications

(80 citation statements)

References 17 publications

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“…Immune checkpoint agents targeting the PD-1/PD-L1 signaling pathway have been successfully applied to the treatment of different types of malignant tumors, including non-small-cell lung cancer [ 18 ], kidney cancer [ 19 ], bladder cancer [ 20 ] and malignant melanoma [ 21 ]. The response to anti-PD-1/PD-L1 treatment could be predicted by expression of PD-L1 within a tumor.…”

Section: Discussionmentioning

confidence: 99%

Retrospective Analysis of the Predictive Value of 18F-FDG PET/CT Metabolic Parameters for PD-L1 Expression in Cervical Cancer

Pang

Song

et al. 2023

Diagnostics

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Background: Immunotherapy targeting PD-1/PD-L1 has been proven to be effective for cervical cancer treatment. To explore non-invasive examinations for assessing the PD-L1 status in cervical cancer, we performed a retrospective study to investigate the predictive value of 18F-FDG PET/CT. Methods: The correlations between PD-L1 expression, clinicopathological characteristics and 18F-FDG PET/CT metabolic parameters were evaluated in 74 cervical cancer patients. The clinicopathological characteristics included age, histologic type, tumor differentiation, FIGO stage and tumor size. The metabolic parameters included maximum standard uptake (SUVmax), mean standard uptake (SUVmean), total lesion glycolysis (TLG) and tumor metabolic volume (MTV). Results: In univariate analysis, SUVmax, SUVmean, TLG, tumor size and tumor differentiation were obviously associated with PD-L1 status. SUVmax (rs = 0.42) and SUVmean (rs = 0.40) were moderately positively correlated with the combined positive score (CPS) for PD-L1 in Spearman correlation analysis. The results of multivariable analysis showed that the higher SUVmax (odds ratio = 2.849) and the lower degree of differentiation (Odds Ratio = 0.168), the greater probability of being PD-L1 positive. The ROC curve analysis demonstrated that when the cut-off values of SUVmax, SUVmean and TLG were 10.45, 6.75 and 143.4, respectively, the highest accuracy for predicting PD-L1 expression was 77.0%, 71.6% and 62.2%, respectively. The comprehensive predictive ability of PD-L1 expression, assessed by combining SUVmax with tumor differentiation, showed that the PD-L1-negative rate was 100% in the low probability group, whereas the PD-L1-positive rate was 84.6% in the high probability group. In addition, we also found that the H-score of HIF-1α was moderately positively correlated with PD-L1 CPS (rs = 0.51). Conclusions: The SUVmax and differentiation of the primary lesion were the optimum predictors for PD-L1 expression in cervical cancer. There was a great potential for 18F-FDG PET/CT in predicting PD-L1 status and selecting cervical cancer candidates for PD1/PD-L1 immune checkpoint therapy.

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Section: Discussionmentioning

confidence: 99%

Retrospective Analysis of the Predictive Value of 18F-FDG PET/CT Metabolic Parameters for PD-L1 Expression in Cervical Cancer

Pang

Song

et al. 2023

Diagnostics

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“…Pembrolizumab also showed better 3.5-year distant metastasis-free survival than placebo treatment for resected stage III melanoma in the intention to treat population (65.3% [95% CI 60.9–69.5%] in the pembrolizumab group vs. 49.4% [44.8–53.8%] in the placebo group; HR 0.60 [95% CI 0.49–0.73]; p < 0.0001) [ 16 ]. In addition, pembrolizumab as adjuvant therapy for up to approximately 1 year for stage IIB or IIC melanoma resulted in a significant prolongation of RFS versus placebo [86% vs. 77%, hazard ratio (HR): 0.60 (95% CI: 0.45–0.79)], with an acceptable safety profile [ 18 ]. Moreover, pembrolizumab in the adjuvant setting for stage IIB or IIC melanoma significantly reduced the onset of distant metastasis versus placebo (6% vs. 12%) [ 18 ].…”

Section: Significance Of the Blockade Of Pd1/pd-l1 Pathways For The T...mentioning

confidence: 99%

“…In addition, pembrolizumab as adjuvant therapy for up to approximately 1 year for stage IIB or IIC melanoma resulted in a significant prolongation of RFS versus placebo [86% vs. 77%, hazard ratio (HR): 0.60 (95% CI: 0.45–0.79)], with an acceptable safety profile [ 18 ]. Moreover, pembrolizumab in the adjuvant setting for stage IIB or IIC melanoma significantly reduced the onset of distant metastasis versus placebo (6% vs. 12%) [ 18 ].…”

Section: Significance Of the Blockade Of Pd1/pd-l1 Pathways For The T...mentioning

confidence: 99%

Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

Fujimura

Muto

Asano

2022

IJMS

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Therapeutic options for treating advanced melanoma have progressed rapidly in recent decades. Until 6 years ago, the regimen for treating advanced melanoma consisted mainly of cytotoxic agents such as dacarbazine and type I interferons. Since 2014, anti-programmed cell death 1 (PD1) antibodies have been recognized as anchor drugs for treating advanced melanoma, with or without additional combination drugs such as ipilimumab, but the efficacies of these immunotherapies are not fully satisfactory. In this review, we describe the development of the currently available anti-PD1 Abs-based immunotherapies for advanced melanoma, focusing on their efficacy and immune-related adverse events (AEs), as well as clinical trials still ongoing for the future treatment of advanced melanoma.

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“…Pembrolizumab and nivolumab are monoclonal antibodies acting as immune checkpoint blockers and have demonstrated clinical efficacy in the treatment of melanoma through inhibition of the programmed cell death protein one (PD-1) receptor [ 3 , 4 , 5 ]. Anti-PD-1 therapy is pivotal in the treatment of invasive melanoma; however, its clinical benefit is limited to a subset of patients and the extent of the clinical response strongly varies between patients [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Revisiting the Role of the CXCL13/CXCR5-Associated Immune Axis in Melanoma: Potential Implications for Anti-PD-1-Related Biomarker Research

Hoellwerth

Koelblinger

Lang

et al. 2023

Life

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CXCL13 is a potent chemoattractant cytokine that promotes the migration of cells expressing its cognate receptor, CXCR5. Accordingly, T follicular helper cells and B cells migrate towards B cell follicles in lymph nodes, where the resulting spatial proximity promotes B cell/T cell interaction and antibody formation. Moreover, effector cells of the CXCL13/CXCR5-associated immune axis express PD-1, with corresponding circulating cells occurring in the blood. The formation of so-called ectopic or tertiary lymphoid structures, recently detected in different cancer types, represents an integral part of this axis, particularly in the context of its emerging role in anti-tumor defense. These aspects of the CXCL13/CXCR5-associated immune axis are highlighted in this review, which focuses on cutaneous malignant melanoma. Specifically, we elaborate on the role of this important immune axis as a possible ancillary target of immune checkpoint inhibition with anti-PD-1 antibodies in different therapeutic settings and as a potential source of predictive biomarkers regarding treatment efficacy.

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Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma (KEYNOTE-716): distant metastasis-free survival results of a multicentre, double-blind, randomised, phase 3 trial

Cited by 103 publications

References 17 publications

Retrospective Analysis of the Predictive Value of 18F-FDG PET/CT Metabolic Parameters for PD-L1 Expression in Cervical Cancer

Retrospective Analysis of the Predictive Value of 18F-FDG PET/CT Metabolic Parameters for PD-L1 Expression in Cervical Cancer

Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

Revisiting the Role of the CXCL13/CXCR5-Associated Immune Axis in Melanoma: Potential Implications for Anti-PD-1-Related Biomarker Research

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