Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial

Dummer, Reinhard; Ascierto, Paolo A.; Gogas, Helen; Arance, Ana; Mandalà, Mario; Liszkay, Gabriella; Garbe, Claus; Schadendorf, Dirk; Krajsová, Ivana; Gutzmer, Ralf; Chiarion-Sileni, Vanna; Dutriaux, Caroline; Groot, Jan Willem B. de; Yamazaki, Naoya; Loquai, Carmen; Parseval, Laure A Moutouh-de; Pickard, Michael D.; Sandor, Victor; Robert, Caroline; Flaherty, Keith T.

doi:10.1016/s1470-2045(18)30497-2

Cited by 466 publications

(418 citation statements)

References 27 publications

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“…Two reports show response to vemurafenib in BRAF V600E ‐mutant HS 18,19 . Additionally, combined BRAF/MEK inhibition has been shown to be more effective than single‐agent BRAF inhibitors in four randomized phase III trials in metastatic melanoma 9–12 …”

mentioning

confidence: 99%

Secondary histiocytic sarcoma with BRAF^V600E mutation after T‐cell acute lymphoblastic leukemia in a very young child with dramatic response to dabrafenib and trametinib

Venkataraman

Massoth

Sullivan

et al. 2020

Pediatric Blood & Cancer

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confidence: 99%

Secondary histiocytic sarcoma with BRAF^V600E mutation after T‐cell acute lymphoblastic leukemia in a very young child with dramatic response to dabrafenib and trametinib

Venkataraman

Massoth

Sullivan

et al. 2020

Pediatric Blood & Cancer

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“…In both parts, the arms were well balanced (Table ). In part 1, COMBO450 significantly improved PFS and OS over vemurafenib (but not encorafenib monotherapy) ; in part 2, COMBO300 demonstrated significantly improved PFS and ORR versus encorafenib monotherapy (therefore showing that binimetinib directly contributes to the efficacy of the combination; Table ) .…”

Section: Resultsmentioning

confidence: 98%

“…These agents include several checkpoint inhibitors—namely, the anti‐cytotoxic T‐lymphocyte associated protein‐4 (anti‐CTLA‐4) antibody ipilimumab and the anti‐programmed death‐1 (anti‐PD‐1) antibodies nivolumab and pembrolizumab—as well as the BRAF inhibitors vemurafenib and dabrafenib and the mitogen‐activated extracellular signal‐regulated kinase (MEK) inhibitors trametinib and cobimetinib . Additional agents that have completed phase III clinical trials for advanced melanoma include the BRAF inhibitor encorafenib, the MEK inhibitor binimetinib, and the oncolytic virus talimogene laherparepvec (T‐VEC) .…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Clinical Trial Data Summation for BRAF-MEK Inhibition and Checkpoint Immunotherapy in Metastatic Melanoma

Luke

2019

The Oncologist

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Background Immune checkpoint inhibitors, along with BRAF and MEK inhibitors, have dramatically changed the management of and outlook for patients with metastatic melanoma. Analyses of long‐term follow‐up data and subanalyses based on disease characteristics may inform clinical decision making. Methods Reports of clinical trials in metastatic melanoma published between January 1, 2012, and August 30, 2018, were identified using PubMed (terms: melanoma AND [dabrafenib OR trametinib OR vemurafenib OR cobimetinib OR encorafenib OR ipilimumab OR nivolumab OR pembrolizumab]) and were systematically reviewed. Relevant congress proceedings were also assessed. Efficacy data from key phase III trials were analyzed and trends identified. Results Substantial improvements in objective response rates, progression‐free survival, and overall survival were documented across 14 identified publications. Subgroup findings supported that patients with lower disease burden derive greater benefit than patients with more advanced disease, limiting the value of disease burden in the clinical decision‐making process. However, these agents consistently conferred benefits despite the presence of poor prognostic features. Several clinically relevant questions remain, including how best to sequence immune checkpoint inhibitors and combination targeted therapy. Conclusion This research, coupled with ongoing investigations, including those on predictive biomarkers, suggests that the treatment decision‐making process is likely to become more nuanced. Implications for Practice The management of melanoma has been rapidly advancing with new classes of agents, including immune checkpoint and BRAF inhibitors. With long‐term follow‐up, their impact on response rates and survival outcomes is well documented. Additional findings from subgroup analyses suggest that patients with lower disease burden derive greater benefit, yet both consistently confer benefit in patients with higher disease burden. Currently, there is a paucity of data to guide first‐line treatment selection between immunotherapy and BRAF‐targeted therapy in clinical practice or to estimate their impact when sequenced. Gaining these insights will facilitate a more nuanced management approach.

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“…However, the duration of clinical response is limited in the majority of patients. Due to drug resistance, disease progression will occur within 6–8 months with BRAFi monotherapy, and within 11–18 months with BRAFi/MEKi combination therapy . Disease progression is the reason most commonly cited for discontinuation of treatment, even though TT is continued in a number of patients once progression has set in.…”

Section: Summary Of Published Data On the Rechallenge Of Targeted Thementioning

confidence: 99%

Rechallenge of targeted therapy in metastatic melanoma

Reschke¹,

Simon²,

Ziemer³

2019

J Deutsche Derma Gesell

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Summary Rechallenge of targeted therapy in patients with BRAFV600‐mutated melanoma plays an important role, because of the prolonged overall survival of melanoma patients. Patients may be rechallenged after a drug‐free interval following adverse drug reactions, after radiation therapy or surgery, following disease progression on subsequent immunotherapy or chemotherapy, or after disease progression without interim therapeutic intervention. To date, only few data has been published on treatment outcomes associated with rechallenge. The articles published on this topic included a total of 238 patients. In general, it was shown that patients did respond to rechallenge, even if they had previously experienced disease progression on targeted therapy. Patient response varied from stable disease to partial response and even complete remission in some cases. Our analysis showed overall response rates to rechallenge of 47 %, with disease control rates of 67 %. While mean progression‐free survival was 6.4 months, this was shorter than after the first round of targeted therapy (mean progression‐free survival of 9.2 months). Rechallenge of targeted therapy offers another option in the management of melanoma patients who have received extensive prior treatment. In particular, it will be important to clarify whether the type of interim treatment has an impact on the response to rechallenge.

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Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial

Cited by 466 publications

References 27 publications

Secondary histiocytic sarcoma with BRAF^V600E mutation after T‐cell acute lymphoblastic leukemia in a very young child with dramatic response to dabrafenib and trametinib

Secondary histiocytic sarcoma with BRAF^V600E mutation after T‐cell acute lymphoblastic leukemia in a very young child with dramatic response to dabrafenib and trametinib

Comprehensive Clinical Trial Data Summation for BRAF-MEK Inhibition and Checkpoint Immunotherapy in Metastatic Melanoma

Rechallenge of targeted therapy in metastatic melanoma

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Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial

Cited by 466 publications

References 27 publications

Secondary histiocytic sarcoma with BRAFV600E mutation after T‐cell acute lymphoblastic leukemia in a very young child with dramatic response to dabrafenib and trametinib

Secondary histiocytic sarcoma with BRAFV600E mutation after T‐cell acute lymphoblastic leukemia in a very young child with dramatic response to dabrafenib and trametinib

Comprehensive Clinical Trial Data Summation for BRAF-MEK Inhibition and Checkpoint Immunotherapy in Metastatic Melanoma

Rechallenge of targeted therapy in metastatic melanoma

Contact Info

Product

Resources

About

Secondary histiocytic sarcoma with BRAF^V600E mutation after T‐cell acute lymphoblastic leukemia in a very young child with dramatic response to dabrafenib and trametinib

Secondary histiocytic sarcoma with BRAF^V600E mutation after T‐cell acute lymphoblastic leukemia in a very young child with dramatic response to dabrafenib and trametinib