COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma

Combined BRAF/MEK-inhibition constitutes a relevant treatment option for <i<BRAF</i<-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in pat...
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Autor*in:	Carola Berking [verfasserIn] Elisabeth Livingstone [verfasserIn] Dirk Debus [verfasserIn] Carmen Loquai [verfasserIn] Michael Weichenthal [verfasserIn] Ulrike Leiter [verfasserIn] Felix Kiecker [verfasserIn] Peter Mohr [verfasserIn] Thomas K. Eigentler [verfasserIn] Janina Remy [verfasserIn] Katharina Schober [verfasserIn] Markus V. Heppt [verfasserIn] Imke von Wasielewski [verfasserIn] Dirk Schadendorf [verfasserIn] Ralf Gutzmer [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	melanoma BRAF mutation MAPK pathway dabrafenib trametinib brain metastases

Übergeordnetes Werk:	In: Cancers - MDPI AG, 2010, 15(2023), 4436, p 4436
Übergeordnetes Werk:	volume:15 ; year:2023 ; number:4436, p 4436

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cancers15184436

Katalog-ID:	DOAJ093441002

Internformat


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allfields	10.3390/cancers15184436 doi (DE-627)DOAJ093441002 (DE-599)DOAJd06b1c350906457c9e3a32544876fb20 DE-627 ger DE-627 rakwb eng RC254-282 Carola Berking verfasserin aut COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Combined BRAF/MEK-inhibition constitutes a relevant treatment option for <i<BRAF</i<-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1–9.3) and the median OS was 18.3 months (14.9–21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9–7.2)) compared with those not requiring corticosteroids (5.9 months (4.8–6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3–11.6)) compared to those who did not (11.9 months (9.6–19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators’ upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials. melanoma BRAF mutation MAPK pathway dabrafenib trametinib brain metastases Neoplasms. Tumors. Oncology. Including cancer and carcinogens Elisabeth Livingstone verfasserin aut Dirk Debus verfasserin aut Carmen Loquai verfasserin aut Michael Weichenthal verfasserin aut Ulrike Leiter verfasserin aut Felix Kiecker verfasserin aut Peter Mohr verfasserin aut Thomas K. Eigentler verfasserin aut Janina Remy verfasserin aut Katharina Schober verfasserin aut Markus V. Heppt verfasserin aut Imke von Wasielewski verfasserin aut Dirk Schadendorf verfasserin aut Ralf Gutzmer verfasserin aut In Cancers MDPI AG, 2010 15(2023), 4436, p 4436 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:15 year:2023 number:4436, p 4436 https://doi.org/10.3390/cancers15184436 kostenfrei https://doaj.org/article/d06b1c350906457c9e3a32544876fb20 kostenfrei https://www.mdpi.com/2072-6694/15/18/4436 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 4436, p 4436
spelling	10.3390/cancers15184436 doi (DE-627)DOAJ093441002 (DE-599)DOAJd06b1c350906457c9e3a32544876fb20 DE-627 ger DE-627 rakwb eng RC254-282 Carola Berking verfasserin aut COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Combined BRAF/MEK-inhibition constitutes a relevant treatment option for <i<BRAF</i<-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1–9.3) and the median OS was 18.3 months (14.9–21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9–7.2)) compared with those not requiring corticosteroids (5.9 months (4.8–6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3–11.6)) compared to those who did not (11.9 months (9.6–19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators’ upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials. melanoma BRAF mutation MAPK pathway dabrafenib trametinib brain metastases Neoplasms. Tumors. Oncology. Including cancer and carcinogens Elisabeth Livingstone verfasserin aut Dirk Debus verfasserin aut Carmen Loquai verfasserin aut Michael Weichenthal verfasserin aut Ulrike Leiter verfasserin aut Felix Kiecker verfasserin aut Peter Mohr verfasserin aut Thomas K. Eigentler verfasserin aut Janina Remy verfasserin aut Katharina Schober verfasserin aut Markus V. Heppt verfasserin aut Imke von Wasielewski verfasserin aut Dirk Schadendorf verfasserin aut Ralf Gutzmer verfasserin aut In Cancers MDPI AG, 2010 15(2023), 4436, p 4436 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:15 year:2023 number:4436, p 4436 https://doi.org/10.3390/cancers15184436 kostenfrei https://doaj.org/article/d06b1c350906457c9e3a32544876fb20 kostenfrei https://www.mdpi.com/2072-6694/15/18/4436 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 4436, p 4436
allfields_unstemmed	10.3390/cancers15184436 doi (DE-627)DOAJ093441002 (DE-599)DOAJd06b1c350906457c9e3a32544876fb20 DE-627 ger DE-627 rakwb eng RC254-282 Carola Berking verfasserin aut COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Combined BRAF/MEK-inhibition constitutes a relevant treatment option for <i<BRAF</i<-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1–9.3) and the median OS was 18.3 months (14.9–21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9–7.2)) compared with those not requiring corticosteroids (5.9 months (4.8–6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3–11.6)) compared to those who did not (11.9 months (9.6–19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators’ upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials. melanoma BRAF mutation MAPK pathway dabrafenib trametinib brain metastases Neoplasms. Tumors. Oncology. Including cancer and carcinogens Elisabeth Livingstone verfasserin aut Dirk Debus verfasserin aut Carmen Loquai verfasserin aut Michael Weichenthal verfasserin aut Ulrike Leiter verfasserin aut Felix Kiecker verfasserin aut Peter Mohr verfasserin aut Thomas K. Eigentler verfasserin aut Janina Remy verfasserin aut Katharina Schober verfasserin aut Markus V. Heppt verfasserin aut Imke von Wasielewski verfasserin aut Dirk Schadendorf verfasserin aut Ralf Gutzmer verfasserin aut In Cancers MDPI AG, 2010 15(2023), 4436, p 4436 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:15 year:2023 number:4436, p 4436 https://doi.org/10.3390/cancers15184436 kostenfrei https://doaj.org/article/d06b1c350906457c9e3a32544876fb20 kostenfrei https://www.mdpi.com/2072-6694/15/18/4436 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 4436, p 4436
allfieldsGer	10.3390/cancers15184436 doi (DE-627)DOAJ093441002 (DE-599)DOAJd06b1c350906457c9e3a32544876fb20 DE-627 ger DE-627 rakwb eng RC254-282 Carola Berking verfasserin aut COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Combined BRAF/MEK-inhibition constitutes a relevant treatment option for <i<BRAF</i<-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1–9.3) and the median OS was 18.3 months (14.9–21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9–7.2)) compared with those not requiring corticosteroids (5.9 months (4.8–6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3–11.6)) compared to those who did not (11.9 months (9.6–19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators’ upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials. melanoma BRAF mutation MAPK pathway dabrafenib trametinib brain metastases Neoplasms. Tumors. Oncology. Including cancer and carcinogens Elisabeth Livingstone verfasserin aut Dirk Debus verfasserin aut Carmen Loquai verfasserin aut Michael Weichenthal verfasserin aut Ulrike Leiter verfasserin aut Felix Kiecker verfasserin aut Peter Mohr verfasserin aut Thomas K. Eigentler verfasserin aut Janina Remy verfasserin aut Katharina Schober verfasserin aut Markus V. Heppt verfasserin aut Imke von Wasielewski verfasserin aut Dirk Schadendorf verfasserin aut Ralf Gutzmer verfasserin aut In Cancers MDPI AG, 2010 15(2023), 4436, p 4436 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:15 year:2023 number:4436, p 4436 https://doi.org/10.3390/cancers15184436 kostenfrei https://doaj.org/article/d06b1c350906457c9e3a32544876fb20 kostenfrei https://www.mdpi.com/2072-6694/15/18/4436 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 4436, p 4436
allfieldsSound	10.3390/cancers15184436 doi (DE-627)DOAJ093441002 (DE-599)DOAJd06b1c350906457c9e3a32544876fb20 DE-627 ger DE-627 rakwb eng RC254-282 Carola Berking verfasserin aut COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Combined BRAF/MEK-inhibition constitutes a relevant treatment option for <i<BRAF</i<-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1–9.3) and the median OS was 18.3 months (14.9–21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9–7.2)) compared with those not requiring corticosteroids (5.9 months (4.8–6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3–11.6)) compared to those who did not (11.9 months (9.6–19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators’ upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials. melanoma BRAF mutation MAPK pathway dabrafenib trametinib brain metastases Neoplasms. Tumors. Oncology. Including cancer and carcinogens Elisabeth Livingstone verfasserin aut Dirk Debus verfasserin aut Carmen Loquai verfasserin aut Michael Weichenthal verfasserin aut Ulrike Leiter verfasserin aut Felix Kiecker verfasserin aut Peter Mohr verfasserin aut Thomas K. Eigentler verfasserin aut Janina Remy verfasserin aut Katharina Schober verfasserin aut Markus V. Heppt verfasserin aut Imke von Wasielewski verfasserin aut Dirk Schadendorf verfasserin aut Ralf Gutzmer verfasserin aut In Cancers MDPI AG, 2010 15(2023), 4436, p 4436 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:15 year:2023 number:4436, p 4436 https://doi.org/10.3390/cancers15184436 kostenfrei https://doaj.org/article/d06b1c350906457c9e3a32544876fb20 kostenfrei https://www.mdpi.com/2072-6694/15/18/4436 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 4436, p 4436
language	English
source	In Cancers 15(2023), 4436, p 4436 volume:15 year:2023 number:4436, p 4436
sourceStr	In Cancers 15(2023), 4436, p 4436 volume:15 year:2023 number:4436, p 4436
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	melanoma BRAF mutation MAPK pathway dabrafenib trametinib brain metastases Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Cancers
authorswithroles_txt_mv	Carola Berking @@aut@@ Elisabeth Livingstone @@aut@@ Dirk Debus @@aut@@ Carmen Loquai @@aut@@ Michael Weichenthal @@aut@@ Ulrike Leiter @@aut@@ Felix Kiecker @@aut@@ Peter Mohr @@aut@@ Thomas K. Eigentler @@aut@@ Janina Remy @@aut@@ Katharina Schober @@aut@@ Markus V. Heppt @@aut@@ Imke von Wasielewski @@aut@@ Dirk Schadendorf @@aut@@ Ralf Gutzmer @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	614095670
id	DOAJ093441002
language_de	englisch
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callnumber-first	R - Medicine
author	Carola Berking
spellingShingle	Carola Berking misc RC254-282 misc melanoma misc BRAF mutation misc MAPK pathway misc dabrafenib misc trametinib misc brain metastases misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma
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topic_title	RC254-282 COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma melanoma BRAF mutation MAPK pathway dabrafenib trametinib brain metastases
topic	misc RC254-282 misc melanoma misc BRAF mutation misc MAPK pathway misc dabrafenib misc trametinib misc brain metastases misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc melanoma misc BRAF mutation misc MAPK pathway misc dabrafenib misc trametinib misc brain metastases misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc melanoma misc BRAF mutation misc MAPK pathway misc dabrafenib misc trametinib misc brain metastases misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma
ctrlnum	(DE-627)DOAJ093441002 (DE-599)DOAJd06b1c350906457c9e3a32544876fb20
title_full	COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma
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author_browse	Carola Berking Elisabeth Livingstone Dirk Debus Carmen Loquai Michael Weichenthal Ulrike Leiter Felix Kiecker Peter Mohr Thomas K. Eigentler Janina Remy Katharina Schober Markus V. Heppt Imke von Wasielewski Dirk Schadendorf Ralf Gutzmer
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author2-role	verfasserin
title_sort	combi-r: a prospective, non-interventional study of dabrafenib plus trametinib in unselected patients with unresectable or metastatic braf v600-mutant melanoma
callnumber	RC254-282
title_auth	COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma
abstract	Combined BRAF/MEK-inhibition constitutes a relevant treatment option for <i<BRAF</i<-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1–9.3) and the median OS was 18.3 months (14.9–21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9–7.2)) compared with those not requiring corticosteroids (5.9 months (4.8–6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3–11.6)) compared to those who did not (11.9 months (9.6–19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators’ upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials.
abstractGer	Combined BRAF/MEK-inhibition constitutes a relevant treatment option for <i<BRAF</i<-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1–9.3) and the median OS was 18.3 months (14.9–21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9–7.2)) compared with those not requiring corticosteroids (5.9 months (4.8–6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3–11.6)) compared to those who did not (11.9 months (9.6–19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators’ upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials.
abstract_unstemmed	Combined BRAF/MEK-inhibition constitutes a relevant treatment option for <i<BRAF</i<-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1–9.3) and the median OS was 18.3 months (14.9–21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9–7.2)) compared with those not requiring corticosteroids (5.9 months (4.8–6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3–11.6)) compared to those who did not (11.9 months (9.6–19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators’ upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials.
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title_short	COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma
url	https://doi.org/10.3390/cancers15184436 https://doaj.org/article/d06b1c350906457c9e3a32544876fb20 https://www.mdpi.com/2072-6694/15/18/4436 https://doaj.org/toc/2072-6694
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