LBA43 Spartalizumab plus dabrafenib and trametinib (Sparta-DabTram) in patients (pts) with previously untreated BRAF V600–mutant unresectable or metastatic melanoma: Results from the randomized part 3 of the phase III COMBI-i trial

Nathan, Paul; Dummer, Reinhard; Long, Georgina V.; Ascierto, Paolo A.; Tawbi, Hussain; Robert, Caroline; Rutkowski, Piotr; Леонов, О. В.; Dutriaux, Caroline; Mandalà, Mario; Lorigan, Paul; Ferrucci, Pier Francesco; Flaherty, Keith T.; Brase, Jan C.; Green, S.; Haas, T; Masood, Aisha; Gasal, Eduard; Ribas, Antoni; Schadendorf, Dirk

doi:10.1016/j.annonc.2020.08.2273

Cited by 66 publications

(54 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast, a recent analysis of part 3 of the COMBI-I trial reported that spartalizumab plus dabrafenib and trametinib did not significantly improve progression-free survival compared with placebo plus dabrafenib and trametinib among patients with previously untreated BRAF V600 -mutant melanoma. 26 In the COMBI-I study, the median progression-free survival was 16.2 months for spartalizumab plus dabrafenib and trametinib versus 12.0 months for placebo plus dabrafenib and trametinib (HR, 0.82; 95% CI 0.655 to 1.027). 26 Median overall survival was not reached in either arm, with analyses ongoing.…”

Section: Discussionmentioning

confidence: 99%

“… 26 In the COMBI-I study, the median progression-free survival was 16.2 months for spartalizumab plus dabrafenib and trametinib versus 12.0 months for placebo plus dabrafenib and trametinib (HR, 0.82; 95% CI 0.655 to 1.027). 26 Median overall survival was not reached in either arm, with analyses ongoing. Grade 3 or higher treatment-related adverse events were reported in 55% of patients receiving spartalizumab plus dabrafenib and trametinib compared with 33% of patients receiving placebo plus dabrafenib and trametinib.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

KEYNOTE-022 part 3: a randomized, double-blind, phase 2 study of pembrolizumab, dabrafenib, and trametinib in BRAF-mutant melanoma

Ferrucci

Giacomo

Vecchio

et al. 2020

J Immunother Cancer

141

127

View full text Add to dashboard Cite

BackgroundIn the KEYNOTE-022 study, pembrolizumab with dabrafenib and trametinib (triplet) improved progression-free survival (PFS) versus placebo with dabrafenib and trametinib (doublet) without reaching statistical significance. Mature results on PFS, duration of response (DOR), and overall survival (OS) are reported.MethodsThe double-blind, phase 2 part of KEYNOTE-022 enrolled patients with previously untreated BRAFV600E/K-mutated advanced melanoma from 22 sites in seven countries. Patients were randomly assigned 1:1 to intravenous pembrolizumab (200 mg every 3 weeks) or placebo plus dabrafenib (150 mg orally two times per day) and trametinib (2 mg orally one time a day). Primary endpoint was PFS. Secondary endpoints were objective response rate, DOR, and OS. Efficacy was assessed in the intention-to-treat population, and safety was assessed in all patients who received at least one dose of study drug. This analysis was not specified in the protocol.ResultsBetween November 30, 2015 and April 24, 2017, 120 patients were randomly assigned to triplet (n=60) or doublet (n=60) therapy. With 36.6 months of follow-up, median PFS was 16.9 months (95% CI 11.3 to 27.9) with triplet and 10.7 months (95% CI 7.2 to 16.8) with doublet (HR 0.53; 95% CI 0.34 to 0.83). With triplet and doublet, respectively, PFS at 24 months was 41.0% (95% CI 27.4% to 54.2%) and 16.3% (95% CI 8.1% to 27.1%); median DOR was 25.1 months (95% CI 14.1 to not reached) and 12.1 months (95% CI 6.0 to 15.7), respectively. Median OS was not reached with triplet and was 26.3 months with doublet (HR 0.64; 95% CI 0.38 to 1.06). With triplet and doublet, respectively, OS at 24 months was 63.0% (95% CI 49.4% to 73.9%) and 51.7% (95% CI 38.4% to 63.4%). Grade 3–5 treatment-related adverse events (TRAEs) occurred in 35 patients (58%, including one death) receiving triplet and 15 patients (25%) receiving doublet.ConclusionIn BRAFV600E/K-mutant advanced melanoma, pembrolizumab plus dabrafenib and trametinib substantially improved PFS, DOR, and OS with a higher incidence of TRAEs. Interpretation of these results is limited by the post hoc nature of the analysis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

KEYNOTE-022 part 3: a randomized, double-blind, phase 2 study of pembrolizumab, dabrafenib, and trametinib in BRAF-mutant melanoma

Ferrucci

Giacomo

Vecchio

et al. 2020

J Immunother Cancer

141

127

View full text Add to dashboard Cite

show abstract

“…In stage IV melanoma, five year overall survival rates obtained with the combination of ipilimumab and nivolumab are currently up to 52% ( 92 ). Three Phase III combination studies in the subset of patients with BRAF V600 mutation using a BRAF plus a MEK inhibitor and immunotherapy with anti-PD-1 or anti-PD-L1 have been carried out ( 93 – 95 ). Although we have not yet obtained data about long term outcomes from these studies, in two out of three trials, progression free survival did not improve in the combo therapy arm of immunotherapy plus targeted therapy over targeted therapy alone and in the third trial there was a modest improvement.…”

Section: Final Considerationsmentioning

confidence: 99%

The Promise of Liquid Biopsy to Predict Response to Immunotherapy in Metastatic Melanoma

et al. 2021

View full text Add to dashboard Cite

Metastatic melanoma is the deadliest form of skin cancer whose incidence has been rising dramatically over the last few decades. Nowadays, the most successful approach in treating advanced melanoma is immunotherapy which encompasses the use of immune checkpoint blockers able to unleash the immune system’s activity against tumor cells. Immunotherapy has dramatically changed clinical practice by contributing to increasing long term overall survival. Despite these striking therapeutic effects, the clinical benefits are strongly mitigated by innate or acquired resistance. In this context, it is of utmost importance to develop methods capable of predicting patient response to immunotherapy. To this purpose, one major step forward may be provided by measuring non-invasive biomarkers in human fluids, namely Liquid Biopsies (LBs). Several LB approaches have been developed over the last few years thanks to technological breakthroughs that have allowed to evaluate circulating components also when they are present in low abundance. The elements of this so-called “circulome” mostly encompass: tumor DNA, tumor and immune cells, soluble factors and non-coding RNAs. Here, we review the current knowledge of these molecules as predictors of response to immunotherapy in metastatic melanoma and predict that LB will soon enter into routine practice in order to guide clinical decisions for cancer immunotherapy.

show abstract

“…However, from the data available, it appears that with longer‐term follow up, immunotherapy may achieve more sustained responses and be more effective when used in the first‐line setting 25,30 . Further studies are ongoing exploring the combinations of immunotherapy plus targeted therapy as another potential treatment approach 39 …”

Section: Systemic Therapy Standards and Updatesmentioning

confidence: 99%

Recent advancements in melanoma management

Krishnan

Menzies

Roberts‐Thomson

2021

Internal Medicine Journal

View full text Add to dashboard Cite

The treatment options for patients with melanoma have expanded significantly over the past decade. In particular, the use of targeted therapy and immunotherapy has dramatically transformed the outlook for patients with advanced disease. These treatments are now being utilised as adjuvant therapy for patients with earlier stage melanoma after surgical resection. We review the latest updates for melanoma staging, surgical resection, radiotherapy and systemic therapies.

show abstract

LBA43 Spartalizumab plus dabrafenib and trametinib (Sparta-DabTram) in patients (pts) with previously untreated BRAF V600–mutant unresectable or metastatic melanoma: Results from the randomized part 3 of the phase III COMBI-i trial

Cited by 66 publications

References 0 publications

KEYNOTE-022 part 3: a randomized, double-blind, phase 2 study of pembrolizumab, dabrafenib, and trametinib in BRAF-mutant melanoma

KEYNOTE-022 part 3: a randomized, double-blind, phase 2 study of pembrolizumab, dabrafenib, and trametinib in BRAF-mutant melanoma

The Promise of Liquid Biopsy to Predict Response to Immunotherapy in Metastatic Melanoma

Recent advancements in melanoma management

Contact Info

Product

Resources

About