Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: New recurrence-free survival results from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial at three-year median follow-up.

Eggermont, Alexander M.M.; Blank, Christian U.; Mandalà, Mario; Long, Georgina V.; Atkinson, Victoria; Dalle, Stéphane; Haydon, Andrew; Meshcheryakov, A. A.; Khattak, Muhammad A.; Carlino, Matteo S.; Sandhu, Shahneen; Puig, Susana; Ascierto, Paolo A.; Akkooi, A.C.J. van; Krepler, Clemens; Ibrahim, Nageatte; Marréaud, Sandrine; Kiciński, Michal; Suciu, Stefan; Robert, Caroline

doi:10.1200/jco.2020.38.15_suppl.10000

Cited by 30 publications

(27 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The three-year follow-up of pembrolizumab’s adjuvant trial Keynote 054 displayed improved recurrence-free survival (RFS) across all subgroups (stages IIIA, IIIB and IIIC; PD-L1 positive and negative; BRAF-mutated and wildtype) [ 26 ]. In the overall population analysis, the pembrolizumab-treated group had a three-year RFS of 64% compared to 44% in the placebo group.…”

Section: Adjuvant Settingmentioning

confidence: 99%

Current Melanoma Treatments: Where Do We Stand?

Moreira

Heinzerling

Bhardwaj

et al. 2021

Cancers

View full text Add to dashboard Cite

Groundbreaking research in immunology and cancer biology in the last few decades has led to the discovery and development of novel therapeutics, such as immune checkpoint inhibitors and targeted therapies, which have revolutionized the clinical care of patients with metastatic melanoma. Updated data from the largest clinical trials continue to support the use of these treatment modalities, both in the metastatic and in adjuvant settings, with studies showing the predicted plateau effect on survival curves. However, with growing evidence that neoadjuvant therapy is also associated with high rates of recurrence-free survival, the question about whether patients should receive adjuvant or neoadjuvant treatment raises new questions about therapeutic options. Finally, management after resistance and intervention with novel immunotherapies are newer challenges, particularly in the field of non-cutaneous melanoma.

show abstract

Section: Adjuvant Settingmentioning

confidence: 99%

Current Melanoma Treatments: Where Do We Stand?

Moreira

Heinzerling

Bhardwaj

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…7 Longterm data regarding relapse-free and overall survival for these agents are not yet available. [6][7][8][9] In the phase 3 COMBI-AD trial involving patients with resected stage III melanoma with BRAF V600E or V600K mutations, 12 months of adjuvant dabrafenib plus trametinib resulted in significantly longer 3-year relapse-free survival than placebo (58% vs. 39%; hazard ratio, 0.47; 95% CI, 0.39 to 0.58; P<0.001). 10,11 The 3-year comparison of overall survival between dabrafenib plus trametinib and placebo (86% vs. 77%; hazard ratio, 0.57; 95% CI, 0.42 to 0.79; P = 0.0006) in a preplanned interim analysis that was based on a 26% information fraction did not reach the prespecified significance threshold of P = 0.000019.…”

mentioning

confidence: 99%

“…Such results are not yet available, since the latest data from the CheckMate 238 and KEYNOTE-054 trials were reported for 3-year analyses. 8,9 Completion lymphadenectomy was part of the inclusion criteria for all three pivotal trials of current standard-of-care adjuvant therapies. 6,7,11 However, based on the results of the Multicenter Selective Lymphadenectomy Trial II (MSLT-II) and the German Dermatologic Cooperative Oncology Group (DeCOG) trial, relevant guidelines have been amended and no longer require completion lymphadenectomy in most patients with stage III disease.…”

mentioning

confidence: 99%

Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background In the previously reported primary analysis of this phase 3 trial, 12 months of adjuvant dabrafenib plus trametinib resulted in significantly longer relapse-free survival than placebo in patients with resected stage III melanoma with BRAF V600E or V600K mutations. To confirm the stability of the relapse-free survival benefit, longer-term data were needed. Methods We randomly assigned 870 patients who had resected stage III melanoma with BRAF V600E or V600K mutations to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. The primary end point was relapse-free survival. Here, we report 5-year results for relapse-free survival and survival without distant metastasis as the site of the first relapse. Overall survival was not analyzed, since the required number of events to trigger the final overall survival analysis had not been reached. Results The minimum duration of follow-up was 59 months (median patient followup, 60 months for dabrafenib plus trametinib and 58 months for placebo). At 5 years, the percentage of patients who were alive without relapse was 52% (95% confidence interval [CI], 48 to 58) with dabrafenib plus trametinib and 36% (95% CI, 32 to 41) with placebo (hazard ratio for relapse or death, 0.51; 95% CI, 0.42 to 0.61). The percentage of patients who were alive without distant metastasis was 65% (95% CI, 61 to 71) with dabrafenib plus trametinib and 54% (95% CI, 49 to 60) with placebo (hazard ratio for distant metastasis or death, 0.55; 95% CI, 0.44 to 0.70). No clinically meaningful between-group difference in the incidence or severity of serious adverse events was reported during the follow-up period. Conclusions In the 5-year follow-up of a phase 3 trial involving patients who had resected stage III melanoma with BRAF V600E or V600K mutations, 12 months of adjuvant therapy with dabrafenib plus trametinib resulted in a longer duration of survival without relapse or distant metastasis than placebo with no apparent longterm toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov number, NCT01682083. opens in new tab; EudraCT number, 2012-001266-15. opens in new tab.

show abstract

“…Another study with an adjuvant anti-PD-1 agent was the EORTC 1325/Keynote 054 study, which randomized stage IIIA (>1 mm), IIIB, and IIIC to either a year of 3-weekly fixed dose pembrolizumab 200 mg or placebo [47]. A recent update of this study by Eggermont et al at ASCO 2020 showed the 3-year RFS rates were 63.7% vs. 44.1% [48].…”

Section: The Current Landscape New Drugs: Immunotherapy (It) and Tarmentioning

confidence: 99%

Adjuvant Therapy for Melanoma: Past, Current, and Future Developments

Testori

Chiellino

Akkooi

2020

Cancers

View full text Add to dashboard Cite

This review describes the progress that the concept of adjuvant therapies has undergone in the last 50 years and focuses on the most recent development where an adjuvant approach has been scientifically evaluated in melanoma clinical trials. Over the past decade the development of immunotherapies and targeted therapies has drastically changed the treatment of stage IV melanoma patients. These successes led to trials studying the same therapies in the adjuvant setting, in high risk resected stage III and IV melanoma patients. Adjuvant immune checkpoint blockade with anti-CTLA-4 antibody ipilimumab was the first drug to show an improvement in recurrence-free and overall survival but this was accompanied by high severe toxicity rates. Therefore, these results were bypassed by adjuvant treatment with anti-PD-1 agents nivolumab and pembrolizumab and BRAF-directed target therapy, which showed even better recurrence-free survival rates with more favorable toxicity rates. The whole concept of adjuvant therapy may be integrated with the new neoadjuvant approaches that are under investigation through several clinical trials. However, there is still no data available on whether the effective adjuvant therapy that patients finally have at their disposal could be offered to them while waiting for recurrence, sparing at least 50% of them a potentially long-term toxic side effect but with the same rate of overall survival (OS). Adjuvant therapy for melanoma has radically changed over the past few years—anti-PD-1 or BRAF-directed therapy is the new standard of care.

show abstract

Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: New recurrence-free survival results from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial at three-year median follow-up.

Cited by 30 publications

References 0 publications

Current Melanoma Treatments: Where Do We Stand?

Current Melanoma Treatments: Where Do We Stand?

Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma

Adjuvant Therapy for Melanoma: Past, Current, and Future Developments

Contact Info

Product

Resources

About