The Experts below are selected from a list of 8370 Experts worldwide ranked by ideXlab platform
Georgina V. Long - One of the best experts on this subject based on the ideXlab platform.
-
Dabrafenib plus trametinib is effective in the treatment of BRAF V600-mutated metastatic melanoma patients: analysis of patients from the Dabrafenib plus trametinib Named Patient Program (DESCRIBE II).
Melanoma research, 2020Co-Authors: Victoria Atkinson, Pier Francesco Ferrucci, Georgina V. Long, Shahneen Sandhu, Geke A.p. Hospers, Massimo Aglietta, Skaiste Tulyte, Gian Carlo Antonini Cappellini, Virtudes Soriano, Sayed AliAbstract:In clinical trials, Dabrafenib plus trametinib improved overall survival (OS) compared with single-agent BRAF inhibitors (BRAFi) in patients with BRAF V600-mutant unresectable or metastatic melanoma. We investigated Dabrafenib plus trametinib therapy in a compassionate-use setting [Named Patient Program (NPP); DESCRIBE II]. A retrospective chart review of patients with BRAF V600-mutated unresectable stage III/IV melanoma receiving Dabrafenib plus trametinib as compassionate use was conducted. Treatment patterns and duration, clinical outcomes, and tolerability were evaluated. Of 271 patients, 92.6% had stage IV melanoma, including 36.5% with brain metastases. Overall, 162 patients (59.8%) were BRAFi naive and 171 (63.1%) received first-line Dabrafenib plus trametinib. Among BRAFi-naive patients, the overall response rate (ORR) was 67.3%, median OS (mOS) was 20.0 months, and median progression-free survival (mPFS) was 7.5 months. In BRAFi-naive patients with known brain metastases (n = 62), ORR was 61.3%, mOS was 15.5 months, and mPFS was 6.2 months. Eighty-four patients received BRAFi monotherapy for >30 days and switched to Dabrafenib plus trametinib prior to progression. Of these 84 patients, 63 had known disease status at the time of switch, and 22 improved with the combination therapy. No new safety signals were identified, and Dabrafenib plus trametinib was well tolerated. Dabrafenib plus trametinib showed substantial clinical activity in NPP patients with BRAF V600-mutated unresectable or metastatic melanoma. Analysis of treatment patterns demonstrated the effectiveness of the combination in patients with brain metastases and across lines of therapy with a well tolerated and manageable safety profile.
-
Dabrafenib plus trametinib versus Dabrafenib monotherapy in patients with metastatic braf v600e k mutant melanoma long term survival and safety analysis of a phase 3 study
Annals of Oncology, 2017Co-Authors: Georgina V. Long, Daniil Stroyakovskiy, Helen Gogas, E Levchenko, F De Braud, James Larkin, Claus Garbe, T Jouary, Keith T Flaherty, Axel HauschildAbstract:ABSTRACT Background Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination Dabrafenib and trametinib versus Dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after ≥36-month follow-up for all living patients. Patients and methods This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive Dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or Dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics. Results Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive Dabrafenib plus trametinib (n= 211) or Dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with Dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on Dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and Conclusions These data demonstrate that durable (≥3 years) survival is achievable with Dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.
-
Dabrafenib plus trametinib versus Dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study.
Annals of oncology : official journal of the European Society for Medical Oncology, 2017Co-Authors: Georgina V. Long, Daniil Stroyakovskiy, Helen Gogas, F De Braud, James Larkin, Claus Garbe, T Jouary, Keith T Flaherty, Evgeny Levchenko, Axel HauschildAbstract:ABSTRACT Background Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination Dabrafenib and trametinib versus Dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after ≥36-month follow-up for all living patients. Patients and methods This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive Dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or Dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics. Results Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive Dabrafenib plus trametinib (n= 211) or Dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with Dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on Dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and Conclusions These data demonstrate that durable (≥3 years) survival is achievable with Dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.
-
Dabrafenib and trametinib versus Dabrafenib and placebo for val600 braf mutant melanoma a multicentre double blind phase 3 randomised controlled trial
The Lancet, 2015Co-Authors: Georgina V. Long, Daniil Stroyakovskiy, Helen Gogas, E Levchenko, F De Braud, James Larkin, Claus Garbe, T Jouary, Axel HauschildAbstract:Summary Background Previously, a study of ours showed that the combination of Dabrafenib and trametinib improves progression-free survival compared with Dabrafenib and placebo in patients with BRAF Val600Lys/Glu mutation-positive metastatic melanoma. The study was continued to assess the secondary endpoint of overall survival, which we report in this Article. Methods We did this double-blind phase 3 study at 113 sites in 14 countries. We enrolled previously untreated patients with BRAF Val600Glu or Val600Lys mutation-positive unresectable stage IIIC or stage IV melanoma. Participants were computer-randomised (1:1) to receive a combination of Dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily), or Dabrafenib and placebo. The primary endpoint was progression-free survival and overall survival was a secondary endpoint. This study is registered with ClinicalTrials.gov, number NCT01584648. Findings Between May 4, 2012, and Nov 30, 2012, we screened 947 patients for eligibility, of whom 423 were randomly assigned to receive Dabrafenib and trametinib (n=211) or Dabrafenib only (n=212). The final data cutoff was Jan 12, 2015, at which time 222 patients had died. Median overall survival was 25·1 months (95% CI 19·2–not reached) in the Dabrafenib and trametinib group versus 18·7 months (15·2–23·7) in the Dabrafenib only group (hazard ratio [HR] 0·71, 95% CI 0·55–0·92; p=0·0107). Overall survival was 74% at 1 year and 51% at 2 years in the Dabrafenib and trametinib group versus 68% and 42%, respectively, in the Dabrafenib only group. Based on 301 events, median progression-free survival was 11·0 months (95% CI 8·0–13·9) in the Dabrafenib and trametinib group and 8·8 months (5·9–9·3) in the Dabrafenib only group (HR 0·67, 95% CI 0·53–0·84; p=0·0004; unadjusted for multiple testing). Treatment-related adverse events occurred in 181 (87%) of 209 patients in the Dabrafenib and trametinib group and 189 (90%) of 211 patients in the Dabrafenib only group; the most common was pyrexia (108 patients, 52%) in the Dabrafenib and trametinib group, and hyperkeratosis (70 patients, 33%) in the Dabrafenib only group. Grade 3 or 4 adverse events occurred in 67 (32%) patients in the Dabrafenib and trametinib group and 66 (31%) patients in the Dabrafenib only group. Interpretation The improvement in overall survival establishes the combination of Dabrafenib and trametinib as the standard targeted treatment for BRAF Val600 mutation-positive melanoma. Studies assessing Dabrafenib and trametinib in combination with immunotherapies are ongoing. Funding GlaxoSmithKline.
-
Updated overall survival (OS) results for BRF113220, a phase I-II study of Dabrafenib alone versus combined Dabrafenib and trametinib in patients with BRAF V600 metastatic melanoma (MM).
Journal of Clinical Oncology, 2015Co-Authors: Adil Daud, Jeffrey R. Infante, Kevin B. Kim, Jeffrey S. Weber, Jeffrey A. Sosman, Rene Gonzalez, Omid Hamid, Jonathan Cebon, Lynn M. Schuchter, Georgina V. LongAbstract:9036 Background: This Phase I—II study evaluated the safety and efficacy of the combination of Dabrafenib and trametinib (the combination) compared with Dabrafenib alone (monotherapy) in patients (...
Axel Hauschild - One of the best experts on this subject based on the ideXlab platform.
-
long term outcomes in patients with braf v600 mutant metastatic melanoma receiving Dabrafenib monotherapy analysis from phase 2 and 3 clinical trials
European Journal of Cancer, 2020Co-Authors: Axel Hauschild, Antoni Ribas, Dirk Schadendorf, C Dutriaux, Paolo A Ascierto, Jean Jacques Grob, Felix Kiecker, Lev V Demidov, Celeste Lebbe, Piotr RutkowskiAbstract:Abstract Background Previous analyses of BREAK-2 and BREAK-3 showed that durable outcomes lasting ≥3 years are achievable with Dabrafenib in some patients with BRAF V600-mutant metastatic melanoma (MM); however, additional follow-up is needed to fully characterise the long-term impact of Dabrafenib in these patients. Methods BREAK-2 was a single-arm phase 2 study evaluating Dabrafenib in treatment-naive or previously treated BRAF V600E/K-mutant MM. BREAK-3, a randomised (3:1) phase 3 study, assessed Dabrafenib versus dacarbazine in previously untreated unresectable or metastatic BRAF V600E-mutant melanoma. Five-year analyses were performed. Results All BREAK-2 patients (N = 92 [V600E, n = 76; V600K, n = 16]) discontinued treatment by the data cutoff. Median follow-up was 13.0 months. In BRAF V600E patients, 5-year progression-free survival (PFS) and overall survival (OS) were 11% and 20%, respectively. Subsequent immunotherapy was received by 22% of patients. In BREAK-3, median follow-up was 17.0 and 12.0 months in the Dabrafenib (n = 187) and dacarbazine (n = 63) arms, respectively. Thirty-seven patients (59%) receiving dacarbazine crossed over to Dabrafenib following disease progression as per protocol. Five-year PFS was 12% in the Dabrafenib arm; all dacarbazine-arm patients progressed or were censored by 5 years. Dabrafenib improved PFS versus dacarbazine, regardless of baseline lactate dehydrogenase levels. Five-year OS rates were 24% and 22% in the Dabrafenib and dacarbazine arms, respectively. Subsequent therapy in each arm included anti–CTLA-4 (Dabrafenib [24%] and dacarbazine [24%]) and/or anti–PD-1 (8% and 2%) treatment. No new safety signals were observed. Conclusions and Relevance These data, representing extended follow-up for Dabrafenib monotherapy, demonstrate that durable benefit lasting ≥5 years is achievable in a subset of patients. Trial registration ClinicalTrials.gov (BREAK-2, NCT01153763; BREAK-3, NCT01227889).
-
patient reported outcomes in patients with resected high risk melanoma with brafv600e or brafv600k mutations treated with adjuvant Dabrafenib plus trametinib combi ad a randomised placebo controlled phase 3 trial
Lancet Oncology, 2019Co-Authors: Dirk Schadendorf, James Larkin, Axel Hauschild, Victoria Atkinson, Mario Santinami, Mario Mandala, Vanna Chiarionsileni, Marta Nyakas, C Dutriaux, Andrew HaydonAbstract:Summary Background In the phase 3 COMBI-AD study, patients with resected, stage III melanoma with BRAF V600E or BRAF V600K mutations received adjuvant Dabrafenib plus trametinib or placebo. The primary analysis showed that Dabrafenib plus trametinib significantly improved relapse-free survival at 3 years. These results led to US Food and Drug Administration approval of Dabrafenib plus trametinib as adjuvant treatment for patients with resected stage III melanoma with BRAF V600E or BRAF V600K mutations. Here, we report the patient-reported outcomes from COMBI-AD. Methods COMBI-AD was a randomised, double-blind, placebo-controlled, phase 3 study done at 169 sites in 25 countries. Study participants were aged 18 years or older and had complete resection of stage IIIA (lymph node metastases >1 mm), IIIB, or IIIC cutaneous melanoma as per American Joint Committee on Cancer 7th edition criteria, with BRAF V600E or BRAF V600K mutations, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) via an interactive voice response system, stratified by mutation type and disease stage, to receive oral Dabrafenib (150 mg twice daily) plus oral trametinib (2 mg once daily) or matching placebos for 12 months. Patients, physicians, and the investigators who analysed the data were masked to treatment allocation. The primary endpoint was relapse-free survival, reported elsewhere. Health-related quality of life, reported here, was a prespecified exploratory endpoint, and was assessed with the European Quality of Life 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire in the intention-to-treat population. We used a mixed-model repeated-measures analysis to assess differences in health-related quality of life between groups. This study is registered with ClinicalTrials.gov, number NCT01682083. The trial is ongoing, but is no longer recruiting participants. Findings Between Jan 31, 2013, and Dec 11, 2014, 870 patients were enrolled and randomly assigned to receive Dabrafenib plus trametinib (n=438) or matching placebos (n=432). Data were collected until the data cutoff for analyses of the primary endpoint (June 30, 2017). The median follow-up was 34 months (IQR 28–39) in the Dabrafenib plus trametinib group and 33 months (20·5–39) in the placebo group. During the 12-month treatment phase, there were no significant or clinically meaningful changes from baseline between groups in EQ-5D-3L visual analogue scale (EQ-VAS) or utility scores. During treatment, there were no clinically meaningful differences in VAS scores or utility scores in the Dabrafenib plus trametinib group between patients who did and did not experience the most common adverse events. During long-term follow-up (range 15–48 months), VAS and utility scores were similar between groups and did not differ from baseline scores. At recurrence, there were significant decreases in VAS scores in both the Dabrafenib plus trametinib group (mean change −6·02, SD 20·57; p=0·0032) and the placebo group (−6·84, 20·86; p Interpretation These findings show that Dabrafenib plus trametinib did not affect patient-reported outcome scores during or after adjuvant treatment, and suggest that preventing or delaying relapse with adjuvant therapy could be beneficial in this setting. Funding Novartis.
-
Dabrafenib plus trametinib versus Dabrafenib monotherapy in patients with metastatic braf v600e k mutant melanoma long term survival and safety analysis of a phase 3 study
Annals of Oncology, 2017Co-Authors: Georgina V. Long, Daniil Stroyakovskiy, Helen Gogas, E Levchenko, F De Braud, James Larkin, Claus Garbe, T Jouary, Keith T Flaherty, Axel HauschildAbstract:ABSTRACT Background Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination Dabrafenib and trametinib versus Dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after ≥36-month follow-up for all living patients. Patients and methods This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive Dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or Dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics. Results Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive Dabrafenib plus trametinib (n= 211) or Dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with Dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on Dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and Conclusions These data demonstrate that durable (≥3 years) survival is achievable with Dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.
-
Dabrafenib plus trametinib versus Dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study.
Annals of oncology : official journal of the European Society for Medical Oncology, 2017Co-Authors: Georgina V. Long, Daniil Stroyakovskiy, Helen Gogas, F De Braud, James Larkin, Claus Garbe, T Jouary, Keith T Flaherty, Evgeny Levchenko, Axel HauschildAbstract:ABSTRACT Background Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination Dabrafenib and trametinib versus Dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after ≥36-month follow-up for all living patients. Patients and methods This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive Dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or Dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics. Results Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive Dabrafenib plus trametinib (n= 211) or Dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with Dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on Dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and Conclusions These data demonstrate that durable (≥3 years) survival is achievable with Dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.
-
Dabrafenib and trametinib versus Dabrafenib and placebo for val600 braf mutant melanoma a multicentre double blind phase 3 randomised controlled trial
The Lancet, 2015Co-Authors: Georgina V. Long, Daniil Stroyakovskiy, Helen Gogas, E Levchenko, F De Braud, James Larkin, Claus Garbe, T Jouary, Axel HauschildAbstract:Summary Background Previously, a study of ours showed that the combination of Dabrafenib and trametinib improves progression-free survival compared with Dabrafenib and placebo in patients with BRAF Val600Lys/Glu mutation-positive metastatic melanoma. The study was continued to assess the secondary endpoint of overall survival, which we report in this Article. Methods We did this double-blind phase 3 study at 113 sites in 14 countries. We enrolled previously untreated patients with BRAF Val600Glu or Val600Lys mutation-positive unresectable stage IIIC or stage IV melanoma. Participants were computer-randomised (1:1) to receive a combination of Dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily), or Dabrafenib and placebo. The primary endpoint was progression-free survival and overall survival was a secondary endpoint. This study is registered with ClinicalTrials.gov, number NCT01584648. Findings Between May 4, 2012, and Nov 30, 2012, we screened 947 patients for eligibility, of whom 423 were randomly assigned to receive Dabrafenib and trametinib (n=211) or Dabrafenib only (n=212). The final data cutoff was Jan 12, 2015, at which time 222 patients had died. Median overall survival was 25·1 months (95% CI 19·2–not reached) in the Dabrafenib and trametinib group versus 18·7 months (15·2–23·7) in the Dabrafenib only group (hazard ratio [HR] 0·71, 95% CI 0·55–0·92; p=0·0107). Overall survival was 74% at 1 year and 51% at 2 years in the Dabrafenib and trametinib group versus 68% and 42%, respectively, in the Dabrafenib only group. Based on 301 events, median progression-free survival was 11·0 months (95% CI 8·0–13·9) in the Dabrafenib and trametinib group and 8·8 months (5·9–9·3) in the Dabrafenib only group (HR 0·67, 95% CI 0·53–0·84; p=0·0004; unadjusted for multiple testing). Treatment-related adverse events occurred in 181 (87%) of 209 patients in the Dabrafenib and trametinib group and 189 (90%) of 211 patients in the Dabrafenib only group; the most common was pyrexia (108 patients, 52%) in the Dabrafenib and trametinib group, and hyperkeratosis (70 patients, 33%) in the Dabrafenib only group. Grade 3 or 4 adverse events occurred in 67 (32%) patients in the Dabrafenib and trametinib group and 66 (31%) patients in the Dabrafenib only group. Interpretation The improvement in overall survival establishes the combination of Dabrafenib and trametinib as the standard targeted treatment for BRAF Val600 mutation-positive melanoma. Studies assessing Dabrafenib and trametinib in combination with immunotherapies are ongoing. Funding GlaxoSmithKline.
Piotr Rutkowski - One of the best experts on this subject based on the ideXlab platform.
-
long term outcomes in patients with braf v600 mutant metastatic melanoma receiving Dabrafenib monotherapy analysis from phase 2 and 3 clinical trials
European Journal of Cancer, 2020Co-Authors: Axel Hauschild, Antoni Ribas, Dirk Schadendorf, C Dutriaux, Paolo A Ascierto, Jean Jacques Grob, Felix Kiecker, Lev V Demidov, Celeste Lebbe, Piotr RutkowskiAbstract:Abstract Background Previous analyses of BREAK-2 and BREAK-3 showed that durable outcomes lasting ≥3 years are achievable with Dabrafenib in some patients with BRAF V600-mutant metastatic melanoma (MM); however, additional follow-up is needed to fully characterise the long-term impact of Dabrafenib in these patients. Methods BREAK-2 was a single-arm phase 2 study evaluating Dabrafenib in treatment-naive or previously treated BRAF V600E/K-mutant MM. BREAK-3, a randomised (3:1) phase 3 study, assessed Dabrafenib versus dacarbazine in previously untreated unresectable or metastatic BRAF V600E-mutant melanoma. Five-year analyses were performed. Results All BREAK-2 patients (N = 92 [V600E, n = 76; V600K, n = 16]) discontinued treatment by the data cutoff. Median follow-up was 13.0 months. In BRAF V600E patients, 5-year progression-free survival (PFS) and overall survival (OS) were 11% and 20%, respectively. Subsequent immunotherapy was received by 22% of patients. In BREAK-3, median follow-up was 17.0 and 12.0 months in the Dabrafenib (n = 187) and dacarbazine (n = 63) arms, respectively. Thirty-seven patients (59%) receiving dacarbazine crossed over to Dabrafenib following disease progression as per protocol. Five-year PFS was 12% in the Dabrafenib arm; all dacarbazine-arm patients progressed or were censored by 5 years. Dabrafenib improved PFS versus dacarbazine, regardless of baseline lactate dehydrogenase levels. Five-year OS rates were 24% and 22% in the Dabrafenib and dacarbazine arms, respectively. Subsequent therapy in each arm included anti–CTLA-4 (Dabrafenib [24%] and dacarbazine [24%]) and/or anti–PD-1 (8% and 2%) treatment. No new safety signals were observed. Conclusions and Relevance These data, representing extended follow-up for Dabrafenib monotherapy, demonstrate that durable benefit lasting ≥5 years is achievable in a subset of patients. Trial registration ClinicalTrials.gov (BREAK-2, NCT01153763; BREAK-3, NCT01227889).
-
Trametinib: a MEK inhibitor for management of metastatic melanoma
OncoTargets and therapy, 2015Co-Authors: Iwona Lugowska, Hanna Koseła-paterczyk, Katarzyna Kozak, Piotr RutkowskiAbstract:This review presents the current data on the efficacy and safety of the selective mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor trametinib in patients with metastatic BRAF V600-positive melanoma. The pharmacological, safety, and efficacy data come from the Phase I, II, and III studies of trametinib monotherapy, as well as those in combination with the BRAF inhibitor Dabrafenib. The most common adverse effects of trametinib therapy are rash, dermatitis, diarrhea, and fatigue. The Phase III METRIC study showed significant improvement in overall survival and progression-free survival in favor of trametinib over standard dacarbazine or paclitaxel chemotherapy. Therefore, trametinib was approved by the US Food and Drug Administration and European Medicines Agency as a single agent for the treatment of patients with V600E-mutated metastatic melanoma. Progression-free survival and response rates for trametinib monotherapy were lower than those noted with BRAF inhibitors. The second step in developing trametinib was to use the combination of trametinib with the BRAF inhibitor, eg, Dabrafenib, to postpone the progression on MEK or BRAF inhibitors. The recently published data showed significant improvement in overall survival and progression-free survival in favor of the combination of trametinib and Dabrafenib over vemurafenib therapy or Dabrafenib alone, with good tolerance. The US Food and Drug Administration has approved the combination of Dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily) for the treatment of patients with BRAF V600E/K-mutant metastatic melanoma, and their use seems to be currently the best approach. While BRAF-MEK inhibition is a standard, molecular targeted therapy in BRAF-mutated melanomas, its future utility has to be established in the rapidly changing landscape of immunotherapeutics.
-
improved overall survival in melanoma with combined Dabrafenib and trametinib
The New England Journal of Medicine, 2015Co-Authors: Caroline Robert, Piotr Rutkowski, Reinhard Dummer, Boguslawa Karaszewska, Jacob Schachter, Andrzej Mackiewicz, Daniil Stroiakovski, Michael Lichinitser, Florent Grange, Laurent MortierAbstract:Background The BRAF inhibitors vemurafenib and Dabrafenib have shown efficacy as monotherapies in patients with previously untreated metastatic melanoma with BRAF V600E or V600K mutations. Combining Dabrafenib and the MEK inhibitor trametinib, as compared with Dabrafenib alone, enhanced antitumor activity in this population of patients. Methods In this open-label, phase 3 trial, we randomly assigned 704 patients with metastatic melanoma with a BRAF V600 mutation to receive either a combination of Dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) or vemurafenib (960 mg twice daily) orally as first-line therapy. The primary end point was overall survival. Results At the preplanned interim overall survival analysis, which was performed after 77% of the total number of expected events occurred, the overall survival rate at 12 months was 72% (95% confidence interval [CI], 67 to 77) in the combination-therapy group and 65% (95% CI, 59 to 70) in the vemurafenib group (hazard ratio for death in the combination-therapy group, 0.69; 95% CI, 0.53 to 0.89; P = 0.005). The prespecified interim stopping boundary was crossed, and the study was stopped for efficacy in July 2014. Median progression-free survival was 11.4 months in the combinationtherapy group and 7.3 months in the vemurafenib group (hazard ratio, 0.56; 95% CI, 0.46 to 0.69; P<0.001). The objective response rate was 64% in the combinationtherapy group and 51% in the vemurafenib group (P<0.001). Rates of severe adverse events and study-drug discontinuations were similar in the two groups. Cutaneous squamous-cell carcinoma and keratoacanthoma occurred in 1% of patients in the combination-therapy group and 18% of those in the vemurafenib group. Conclusions Dabrafenib plus trametinib, as compared with vemurafenib monotherapy, significantly improved overall survival in previously untreated patients with metastatic melanoma with BRAF V600E or V600K mutations, without increased overall toxicity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT01597908.)
-
Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib
The New England journal of medicine, 2014Co-Authors: Caroline Robert, Piotr Rutkowski, Reinhard Dummer, Boguslawa Karaszewska, Jacob Schachter, Andrzej Mackiewicz, Daniil Stroiakovski, Michael Lichinitser, Florent Grange, Laurent MortierAbstract:Background The BRAF inhibitors vemurafenib and Dabrafenib have shown efficacy as monotherapies in patients with previously untreated metastatic melanoma with BRAF V600E or V600K mutations. Combining Dabrafenib and the MEK inhibitor trametinib, as compared with Dabrafenib alone, enhanced antitumor activity in this population of patients. Methods In this open-label, phase 3 trial, we randomly assigned 704 patients with metastatic melanoma with a BRAF V600 mutation to receive either a combination of Dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) or vemurafenib (960 mg twice daily) orally as first-line therapy. The primary end point was overall survival. Results At the preplanned interim overall survival analysis, which was performed after 77% of the total number of expected events occurred, the overall survival rate at 12 months was 72% (95% confidence interval [CI], 67 to 77) in the combination-therapy group and 65% (95% CI, 59 to 70) in the vemurafenib group (hazard ratio for death in the combination-therapy group, 0.69; 95% CI, 0.53 to 0.89; P = 0.005). The prespecified interim stopping boundary was crossed, and the study was stopped for efficacy in July 2014. Median progression-free survival was 11.4 months in the combinationtherapy group and 7.3 months in the vemurafenib group (hazard ratio, 0.56; 95% CI, 0.46 to 0.69; P
-
Dabrafenib for the treatment of BRAF V600-positive melanoma: a safety evaluation
Expert opinion on drug safety, 2014Co-Authors: Piotr Rutkowski, Christian U. BlankAbstract:Introduction: V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors are emerging as the standard of care for treating advanced melanomas harboring the BRAF V600 oncogenic mutation. Dabrafenib is the second approved selective BRAF inhibitor (after vemurafenib) for the treatment of unresectable or metastatic BRAF V600-positive melanoma.Areas covered: This review covers the current data on the efficacy and safety of the selective BRAF inhibitor Dabrafenib in patients with metastatic BRAF V600 positive melanoma. The pharmacological, safety and efficacy data are discussed from Phase I, II, and III studies of Dabrafenib monotherapy as well as in combination with the MEK inhibitor trametinib.Expert opinion: Dabrafenib has demonstrated comparable efficacy to vemurafenib in BRAF V600E mutant melanoma patients. Dabrafenib is well tolerated in patients with metastatic melanoma, including patients with brain metastases. Nevertheless side effects are common, but usually manageable. In the Phase III study te...
James Larkin - One of the best experts on this subject based on the ideXlab platform.
-
patient reported outcomes in patients with resected high risk melanoma with brafv600e or brafv600k mutations treated with adjuvant Dabrafenib plus trametinib combi ad a randomised placebo controlled phase 3 trial
Lancet Oncology, 2019Co-Authors: Dirk Schadendorf, James Larkin, Axel Hauschild, Victoria Atkinson, Mario Santinami, Mario Mandala, Vanna Chiarionsileni, Marta Nyakas, C Dutriaux, Andrew HaydonAbstract:Summary Background In the phase 3 COMBI-AD study, patients with resected, stage III melanoma with BRAF V600E or BRAF V600K mutations received adjuvant Dabrafenib plus trametinib or placebo. The primary analysis showed that Dabrafenib plus trametinib significantly improved relapse-free survival at 3 years. These results led to US Food and Drug Administration approval of Dabrafenib plus trametinib as adjuvant treatment for patients with resected stage III melanoma with BRAF V600E or BRAF V600K mutations. Here, we report the patient-reported outcomes from COMBI-AD. Methods COMBI-AD was a randomised, double-blind, placebo-controlled, phase 3 study done at 169 sites in 25 countries. Study participants were aged 18 years or older and had complete resection of stage IIIA (lymph node metastases >1 mm), IIIB, or IIIC cutaneous melanoma as per American Joint Committee on Cancer 7th edition criteria, with BRAF V600E or BRAF V600K mutations, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) via an interactive voice response system, stratified by mutation type and disease stage, to receive oral Dabrafenib (150 mg twice daily) plus oral trametinib (2 mg once daily) or matching placebos for 12 months. Patients, physicians, and the investigators who analysed the data were masked to treatment allocation. The primary endpoint was relapse-free survival, reported elsewhere. Health-related quality of life, reported here, was a prespecified exploratory endpoint, and was assessed with the European Quality of Life 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire in the intention-to-treat population. We used a mixed-model repeated-measures analysis to assess differences in health-related quality of life between groups. This study is registered with ClinicalTrials.gov, number NCT01682083. The trial is ongoing, but is no longer recruiting participants. Findings Between Jan 31, 2013, and Dec 11, 2014, 870 patients were enrolled and randomly assigned to receive Dabrafenib plus trametinib (n=438) or matching placebos (n=432). Data were collected until the data cutoff for analyses of the primary endpoint (June 30, 2017). The median follow-up was 34 months (IQR 28–39) in the Dabrafenib plus trametinib group and 33 months (20·5–39) in the placebo group. During the 12-month treatment phase, there were no significant or clinically meaningful changes from baseline between groups in EQ-5D-3L visual analogue scale (EQ-VAS) or utility scores. During treatment, there were no clinically meaningful differences in VAS scores or utility scores in the Dabrafenib plus trametinib group between patients who did and did not experience the most common adverse events. During long-term follow-up (range 15–48 months), VAS and utility scores were similar between groups and did not differ from baseline scores. At recurrence, there were significant decreases in VAS scores in both the Dabrafenib plus trametinib group (mean change −6·02, SD 20·57; p=0·0032) and the placebo group (−6·84, 20·86; p Interpretation These findings show that Dabrafenib plus trametinib did not affect patient-reported outcome scores during or after adjuvant treatment, and suggest that preventing or delaying relapse with adjuvant therapy could be beneficial in this setting. Funding Novartis.
-
Dabrafenib plus trametinib versus Dabrafenib monotherapy in patients with metastatic braf v600e k mutant melanoma long term survival and safety analysis of a phase 3 study
Annals of Oncology, 2017Co-Authors: Georgina V. Long, Daniil Stroyakovskiy, Helen Gogas, E Levchenko, F De Braud, James Larkin, Claus Garbe, T Jouary, Keith T Flaherty, Axel HauschildAbstract:ABSTRACT Background Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination Dabrafenib and trametinib versus Dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after ≥36-month follow-up for all living patients. Patients and methods This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive Dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or Dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics. Results Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive Dabrafenib plus trametinib (n= 211) or Dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with Dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on Dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and Conclusions These data demonstrate that durable (≥3 years) survival is achievable with Dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.
-
Dabrafenib plus trametinib versus Dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study.
Annals of oncology : official journal of the European Society for Medical Oncology, 2017Co-Authors: Georgina V. Long, Daniil Stroyakovskiy, Helen Gogas, F De Braud, James Larkin, Claus Garbe, T Jouary, Keith T Flaherty, Evgeny Levchenko, Axel HauschildAbstract:ABSTRACT Background Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination Dabrafenib and trametinib versus Dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after ≥36-month follow-up for all living patients. Patients and methods This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive Dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or Dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics. Results Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive Dabrafenib plus trametinib (n= 211) or Dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with Dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on Dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and Conclusions These data demonstrate that durable (≥3 years) survival is achievable with Dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.
-
Combination Dabrafenib and trametinib in the management of advanced melanoma with BRAFV600 mutations
Expert opinion on pharmacotherapy, 2016Co-Authors: Lavinia Spain, Maximilian Julve, James LarkinAbstract:ABSTRACTIntroduction: In the 40–50% of advanced melanoma patients with tumors harboring BRAF V600E and V600 K mutations, BRAF inhibitors such as Dabrafenib are a highly effective treatment. However, most patients develop resistance after several months on treatment. The addition of a MEK inhibitor, such as trametinib, to BRAF inhibition mitigates one key pathway of resistance, further increasing response rates and improving survival.Areas covered: This article summarizes the mechanism of action of the combination of Dabrafenib and trametinib, its evolution through Phase I, II and III clinical trials and discusses its current use in the management of patients with advanced melanoma.Expert opinion: Combination therapy with Dabrafenib and trametinib improves response rate, progression-free survival and overall survival when compared to Dabrafenib or vemurafenib alone. The addition of trametinib to Dabrafenib changes the adverse event profile, making hyperkeratosis and cutaneous squamous cell carcinomas less ...
-
Dabrafenib and trametinib versus Dabrafenib and placebo for val600 braf mutant melanoma a multicentre double blind phase 3 randomised controlled trial
The Lancet, 2015Co-Authors: Georgina V. Long, Daniil Stroyakovskiy, Helen Gogas, E Levchenko, F De Braud, James Larkin, Claus Garbe, T Jouary, Axel HauschildAbstract:Summary Background Previously, a study of ours showed that the combination of Dabrafenib and trametinib improves progression-free survival compared with Dabrafenib and placebo in patients with BRAF Val600Lys/Glu mutation-positive metastatic melanoma. The study was continued to assess the secondary endpoint of overall survival, which we report in this Article. Methods We did this double-blind phase 3 study at 113 sites in 14 countries. We enrolled previously untreated patients with BRAF Val600Glu or Val600Lys mutation-positive unresectable stage IIIC or stage IV melanoma. Participants were computer-randomised (1:1) to receive a combination of Dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily), or Dabrafenib and placebo. The primary endpoint was progression-free survival and overall survival was a secondary endpoint. This study is registered with ClinicalTrials.gov, number NCT01584648. Findings Between May 4, 2012, and Nov 30, 2012, we screened 947 patients for eligibility, of whom 423 were randomly assigned to receive Dabrafenib and trametinib (n=211) or Dabrafenib only (n=212). The final data cutoff was Jan 12, 2015, at which time 222 patients had died. Median overall survival was 25·1 months (95% CI 19·2–not reached) in the Dabrafenib and trametinib group versus 18·7 months (15·2–23·7) in the Dabrafenib only group (hazard ratio [HR] 0·71, 95% CI 0·55–0·92; p=0·0107). Overall survival was 74% at 1 year and 51% at 2 years in the Dabrafenib and trametinib group versus 68% and 42%, respectively, in the Dabrafenib only group. Based on 301 events, median progression-free survival was 11·0 months (95% CI 8·0–13·9) in the Dabrafenib and trametinib group and 8·8 months (5·9–9·3) in the Dabrafenib only group (HR 0·67, 95% CI 0·53–0·84; p=0·0004; unadjusted for multiple testing). Treatment-related adverse events occurred in 181 (87%) of 209 patients in the Dabrafenib and trametinib group and 189 (90%) of 211 patients in the Dabrafenib only group; the most common was pyrexia (108 patients, 52%) in the Dabrafenib and trametinib group, and hyperkeratosis (70 patients, 33%) in the Dabrafenib only group. Grade 3 or 4 adverse events occurred in 67 (32%) patients in the Dabrafenib and trametinib group and 66 (31%) patients in the Dabrafenib only group. Interpretation The improvement in overall survival establishes the combination of Dabrafenib and trametinib as the standard targeted treatment for BRAF Val600 mutation-positive melanoma. Studies assessing Dabrafenib and trametinib in combination with immunotherapies are ongoing. Funding GlaxoSmithKline.
Adil Daud - One of the best experts on this subject based on the ideXlab platform.
-
indirect treatment comparison of Dabrafenib plus trametinib versus vemurafenib plus cobimetinib in previously untreated metastatic melanoma patients
Journal of Hematology & Oncology, 2017Co-Authors: Adil Daud, Japinder Gill, Sheily Kamra, Lei Chen, Amit AhujaAbstract:Metastatic melanoma is an aggressive form of skin cancer with a high mortality rate and the fastest growing global incidence rate of all malignancies. The introduction of BRAF/MEK inhibitor combinations has yielded significant increases in PFS and OS for melanoma. However, at present, no direct comparisons between different BRAF/MEK combinations have been conducted. In light of this, an indirect treatment comparison was performed between two BRAF/MEK inhibitor combination therapies for metastatic melanoma, Dabrafenib plus trametinib and vemurafenib plus cobimetinib, in order to understand the relative efficacy and toxicity profiles of these therapies. A systematic literature search identified two randomized trials as suitable for indirect comparison: the coBRIM trial of vemurafenib plus cobimetinib versus vemurafenib and the COMBI-v trial of Dabrafenib plus trametinib versus vemurafenib. The comparison followed the method of Bucher et al. and analyzed both efficacy (overall survival [OS], progression-free survival [PFS], and overall response rate [ORR]) and safety outcomes (adverse events [AEs]). The indirect comparison revealed similar efficacy outcomes between both therapies, with no statistically significant difference between therapies for OS (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.68 − 1.30), PFS (HR 1.05, 95% CI 0.79 − 1.40), or ORR (risk ratio [RR] 0.90, 95% CI 0.74 − 1.10). Dabrafenib plus trametinib differed significantly from vemurafenib plus cobimetinib with regard to the incidence of treatment-related AE (RR 0.92, 95% CI 0.87 − 0.97), any AE grade ≥3 (RR 0.71, 95% CI 0.60 − 0.85) or dose interruption/modification (RR 0.77, 95% CI 0.60 − 0.99). Several categories of AEs occurred significantly more frequently with vemurafenib plus cobimetinib, while some occurred significantly more frequently with Dabrafenib plus trametinib. For severe AEs (grade 3 or above), four occurred significantly more frequently with vemurafenib plus cobimetinib and no severe AE occurred significantly more frequently with Dabrafenib plus trametinib. This indirect treatment comparison suggested that Dabrafenib plus trametinib had comparable efficacy to vemurafenib plus cobimetinib but was associated with reduced adverse events.
-
Indirect treatment comparison of Dabrafenib plus trametinib versus vemurafenib plus cobimetinib in previously untreated metastatic melanoma patients
Journal of Hematology & Oncology, 2017Co-Authors: Adil Daud, Japinder Gill, Sheily Kamra, Lei Chen, Amit AhujaAbstract:Background Metastatic melanoma is an aggressive form of skin cancer with a high mortality rate and the fastest growing global incidence rate of all malignancies. The introduction of BRAF/MEK inhibitor combinations has yielded significant increases in PFS and OS for melanoma. However, at present, no direct comparisons between different BRAF/MEK combinations have been conducted. In light of this, an indirect treatment comparison was performed between two BRAF/MEK inhibitor combination therapies for metastatic melanoma, Dabrafenib plus trametinib and vemurafenib plus cobimetinib, in order to understand the relative efficacy and toxicity profiles of these therapies. Methods A systematic literature search identified two randomized trials as suitable for indirect comparison: the coBRIM trial of vemurafenib plus cobimetinib versus vemurafenib and the COMBI-v trial of Dabrafenib plus trametinib versus vemurafenib. The comparison followed the method of Bucher et al. and analyzed both efficacy (overall survival [OS], progression-free survival [PFS], and overall response rate [ORR]) and safety outcomes (adverse events [AEs]). Results The indirect comparison revealed similar efficacy outcomes between both therapies, with no statistically significant difference between therapies for OS (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.68 − 1.30), PFS (HR 1.05, 95% CI 0.79 − 1.40), or ORR (risk ratio [RR] 0.90, 95% CI 0.74 − 1.10). Dabrafenib plus trametinib differed significantly from vemurafenib plus cobimetinib with regard to the incidence of treatment-related AE (RR 0.92, 95% CI 0.87 − 0.97), any AE grade ≥3 (RR 0.71, 95% CI 0.60 − 0.85) or dose interruption/modification (RR 0.77, 95% CI 0.60 − 0.99). Several categories of AEs occurred significantly more frequently with vemurafenib plus cobimetinib, while some occurred significantly more frequently with Dabrafenib plus trametinib. For severe AEs (grade 3 or above), four occurred significantly more frequently with vemurafenib plus cobimetinib and no severe AE occurred significantly more frequently with Dabrafenib plus trametinib. Conclusions This indirect treatment comparison suggested that Dabrafenib plus trametinib had comparable efficacy to vemurafenib plus cobimetinib but was associated with reduced adverse events.
-
Updated overall survival (OS) results for BRF113220, a phase I-II study of Dabrafenib alone versus combined Dabrafenib and trametinib in patients with BRAF V600 metastatic melanoma (MM).
Journal of Clinical Oncology, 2015Co-Authors: Adil Daud, Jeffrey R. Infante, Kevin B. Kim, Jeffrey S. Weber, Jeffrey A. Sosman, Rene Gonzalez, Omid Hamid, Jonathan Cebon, Lynn M. Schuchter, Georgina V. LongAbstract:9036 Background: This Phase I—II study evaluated the safety and efficacy of the combination of Dabrafenib and trametinib (the combination) compared with Dabrafenib alone (monotherapy) in patients (...