BRAF +/- MEK inhibition following pembrolizumab (pembro) in KEYNOTE-006

G V Long; L Mortier; M Lotem; J J Grob; A Ribas; B Neyns; C Lebbe; P Mohr; A M Arance Fernandez; M S Carlino; P Lorigan; M Middleton; J Schachter; E Walpole; C U Blank; E Jensen; M A Leiby; N Ibrahim; C Robert

doi:10.1111/pcmr.12656

Abstract

The efficacy of BRAF+MEK inhibition as first-line therapy for BRAF^V600-mutant melanoma is well established. In the KEYNOTE-006 study of pembro 10 mg/kg Q2W or Q3W versus ipilimumab 3 mg/kg Q3W for patients (pts) with advanced melanoma (NCT01866319), ORR in the pooled pembro arms was 38% for BRAF^V600 wild type (n = 355) and 32% for BRAF^V600 mutant (n = 195) disease. We assessed the activity of BRAF +/- MEK inhibition as the first subsequent therapy following pembro in KEYNOTE-006. As of Nov 3, 2016, 30 pts received BRAF+MEK inhibition and 29 pts received BRAF inhibition alone as their first subsequent therapy after pembro. All 59 pts had BRAF^V600-mutant disease, 68% had M1c disease, 15% had elevated LDH, and 5% had brain metastases at study baseline; 36% of pts received BRAF +/- MEK inhibitors before study entry. Pts received pembro for a median 12.3 week (range, 0.1-100.3) with best re-sponse (central RECIST v1.1) of PR in 14%, SD in 14%, nonCR/nonPD in 3%, PD in 63%, and nonevaluable/unknown in 7%. Median interval between pembro and BRAF +/- MEK inhibition was 3.3 week (range, 0.1-65.7). Median duration of subsequent BRAF +/- MEK inhibition was 28.3 week (range, 1.6-136.1). Reported ORR for BRAF +/- MEK inhibition was 31% overall, 30% for BRAF+MEK and 31% for BRAF alone; ORR was 10% in pts with prior BRAF +/- MEK and 42% in pts without. Best response to subsequent BRAF +/- MEK inhibition was CR in 8%, PR in 22%, SD in 34%, PD in 29%, and nonevaluable/unknown in 7%; subsequent PD occurred in 0% of CRs, 54% of PRs, and 70% of SDs. 38 of the 59 pts had died, and median OS from randomization was 17.9 months (95% CI, 14.9-31.2). Although ORR in this post-hoc, exploratory analysis is less than that observed in phase 3 trials of first-line BRAF +/- MEK inhibition, BRAF +/- MEK inhibition appears to have antitumor activity following pembro in pts with advanced BRAF^V600-mutant melanoma, particularly in those without prior BRAF +/- MEK therapy.

Original language	English
Pages (from-to)	182
Journal	Pigment Cell and Melanoma Research
Volume	31 (1)
DOIs	https://doi.org/10.1111/pcmr.12656
Publication status	Published - 2018

Keywords

adult antineoplastic activity brain metastasis con

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/pcmr.12656

Cite this

Long, G. V., Mortier, L., Lotem, M., Grob, J. J., Ribas, A., Neyns, B., Lebbe, C., Mohr, P., Arance Fernandez, A. M., Carlino, M. S., Lorigan, P., Middleton, M., Schachter, J., Walpole, E., Blank, C. U., Jensen, E., Leiby, M. A., Ibrahim, N., & Robert, C. (2018). BRAF +/- MEK inhibition following pembrolizumab (pembro) in KEYNOTE-006. Pigment Cell and Melanoma Research, 31 (1), 182. https://doi.org/10.1111/pcmr.12656

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title = "BRAF +/- MEK inhibition following pembrolizumab (pembro) in KEYNOTE-006",

abstract = "The efficacy of BRAF+MEK inhibition as first-line therapy for BRAFV600-mutant melanoma is well established. In the KEYNOTE-006 study of pembro 10 mg/kg Q2W or Q3W versus ipilimumab 3 mg/kg Q3W for patients (pts) with advanced melanoma (NCT01866319), ORR in the pooled pembro arms was 38% for BRAFV600 wild type (n = 355) and 32% for BRAFV600 mutant (n = 195) disease. We assessed the activity of BRAF +/- MEK inhibition as the first subsequent therapy following pembro in KEYNOTE-006. As of Nov 3, 2016, 30 pts received BRAF+MEK inhibition and 29 pts received BRAF inhibition alone as their first subsequent therapy after pembro. All 59 pts had BRAFV600-mutant disease, 68% had M1c disease, 15% had elevated LDH, and 5% had brain metastases at study baseline; 36% of pts received BRAF +/- MEK inhibitors before study entry. Pts received pembro for a median 12.3 week (range, 0.1-100.3) with best re-sponse (central RECIST v1.1) of PR in 14%, SD in 14%, nonCR/nonPD in 3%, PD in 63%, and nonevaluable/unknown in 7%. Median interval between pembro and BRAF +/- MEK inhibition was 3.3 week (range, 0.1-65.7). Median duration of subsequent BRAF +/- MEK inhibition was 28.3 week (range, 1.6-136.1). Reported ORR for BRAF +/- MEK inhibition was 31% overall, 30% for BRAF+MEK and 31% for BRAF alone; ORR was 10% in pts with prior BRAF +/- MEK and 42% in pts without. Best response to subsequent BRAF +/- MEK inhibition was CR in 8%, PR in 22%, SD in 34%, PD in 29%, and nonevaluable/unknown in 7%; subsequent PD occurred in 0% of CRs, 54% of PRs, and 70% of SDs. 38 of the 59 pts had died, and median OS from randomization was 17.9 months (95% CI, 14.9-31.2). Although ORR in this post-hoc, exploratory analysis is less than that observed in phase 3 trials of first-line BRAF +/- MEK inhibition, BRAF +/- MEK inhibition appears to have antitumor activity following pembro in pts with advanced BRAFV600-mutant melanoma, particularly in those without prior BRAF +/- MEK therapy.",

keywords = "adult antineoplastic activity brain metastasis con",

author = "Long, {G V} and L Mortier and M Lotem and Grob, {J J} and A Ribas and B Neyns and C Lebbe and P Mohr and {Arance Fernandez}, {A M} and Carlino, {M S} and P Lorigan and M Middleton and J Schachter and E Walpole and Blank, {C U} and E Jensen and Leiby, {M A} and N Ibrahim and C Robert",

year = "2018",

doi = "10.1111/pcmr.12656",

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volume = "31 (1)",

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journal = "Pigment Cell and Melanoma Research",

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Long, GV, Mortier, L, Lotem, M, Grob, JJ, Ribas, A, Neyns, B, Lebbe, C, Mohr, P, Arance Fernandez, AM, Carlino, MS, Lorigan, P, Middleton, M, Schachter, J, Walpole, E, Blank, CU, Jensen, E, Leiby, MA, Ibrahim, N & Robert, C 2018, 'BRAF +/- MEK inhibition following pembrolizumab (pembro) in KEYNOTE-006', Pigment Cell and Melanoma Research, vol. 31 (1), pp. 182. https://doi.org/10.1111/pcmr.12656

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T1 - BRAF +/- MEK inhibition following pembrolizumab (pembro) in KEYNOTE-006

AU - Long, G V

AU - Mortier, L

AU - Lotem, M

AU - Grob, J J

AU - Ribas, A

AU - Neyns, B

AU - Lebbe, C

AU - Mohr, P

AU - Arance Fernandez, A M

AU - Carlino, M S

AU - Lorigan, P

AU - Middleton, M

AU - Schachter, J

AU - Walpole, E

AU - Blank, C U

AU - Jensen, E

AU - Leiby, M A

AU - Ibrahim, N

AU - Robert, C

PY - 2018

Y1 - 2018

N2 - The efficacy of BRAF+MEK inhibition as first-line therapy for BRAFV600-mutant melanoma is well established. In the KEYNOTE-006 study of pembro 10 mg/kg Q2W or Q3W versus ipilimumab 3 mg/kg Q3W for patients (pts) with advanced melanoma (NCT01866319), ORR in the pooled pembro arms was 38% for BRAFV600 wild type (n = 355) and 32% for BRAFV600 mutant (n = 195) disease. We assessed the activity of BRAF +/- MEK inhibition as the first subsequent therapy following pembro in KEYNOTE-006. As of Nov 3, 2016, 30 pts received BRAF+MEK inhibition and 29 pts received BRAF inhibition alone as their first subsequent therapy after pembro. All 59 pts had BRAFV600-mutant disease, 68% had M1c disease, 15% had elevated LDH, and 5% had brain metastases at study baseline; 36% of pts received BRAF +/- MEK inhibitors before study entry. Pts received pembro for a median 12.3 week (range, 0.1-100.3) with best re-sponse (central RECIST v1.1) of PR in 14%, SD in 14%, nonCR/nonPD in 3%, PD in 63%, and nonevaluable/unknown in 7%. Median interval between pembro and BRAF +/- MEK inhibition was 3.3 week (range, 0.1-65.7). Median duration of subsequent BRAF +/- MEK inhibition was 28.3 week (range, 1.6-136.1). Reported ORR for BRAF +/- MEK inhibition was 31% overall, 30% for BRAF+MEK and 31% for BRAF alone; ORR was 10% in pts with prior BRAF +/- MEK and 42% in pts without. Best response to subsequent BRAF +/- MEK inhibition was CR in 8%, PR in 22%, SD in 34%, PD in 29%, and nonevaluable/unknown in 7%; subsequent PD occurred in 0% of CRs, 54% of PRs, and 70% of SDs. 38 of the 59 pts had died, and median OS from randomization was 17.9 months (95% CI, 14.9-31.2). Although ORR in this post-hoc, exploratory analysis is less than that observed in phase 3 trials of first-line BRAF +/- MEK inhibition, BRAF +/- MEK inhibition appears to have antitumor activity following pembro in pts with advanced BRAFV600-mutant melanoma, particularly in those without prior BRAF +/- MEK therapy.

AB - The efficacy of BRAF+MEK inhibition as first-line therapy for BRAFV600-mutant melanoma is well established. In the KEYNOTE-006 study of pembro 10 mg/kg Q2W or Q3W versus ipilimumab 3 mg/kg Q3W for patients (pts) with advanced melanoma (NCT01866319), ORR in the pooled pembro arms was 38% for BRAFV600 wild type (n = 355) and 32% for BRAFV600 mutant (n = 195) disease. We assessed the activity of BRAF +/- MEK inhibition as the first subsequent therapy following pembro in KEYNOTE-006. As of Nov 3, 2016, 30 pts received BRAF+MEK inhibition and 29 pts received BRAF inhibition alone as their first subsequent therapy after pembro. All 59 pts had BRAFV600-mutant disease, 68% had M1c disease, 15% had elevated LDH, and 5% had brain metastases at study baseline; 36% of pts received BRAF +/- MEK inhibitors before study entry. Pts received pembro for a median 12.3 week (range, 0.1-100.3) with best re-sponse (central RECIST v1.1) of PR in 14%, SD in 14%, nonCR/nonPD in 3%, PD in 63%, and nonevaluable/unknown in 7%. Median interval between pembro and BRAF +/- MEK inhibition was 3.3 week (range, 0.1-65.7). Median duration of subsequent BRAF +/- MEK inhibition was 28.3 week (range, 1.6-136.1). Reported ORR for BRAF +/- MEK inhibition was 31% overall, 30% for BRAF+MEK and 31% for BRAF alone; ORR was 10% in pts with prior BRAF +/- MEK and 42% in pts without. Best response to subsequent BRAF +/- MEK inhibition was CR in 8%, PR in 22%, SD in 34%, PD in 29%, and nonevaluable/unknown in 7%; subsequent PD occurred in 0% of CRs, 54% of PRs, and 70% of SDs. 38 of the 59 pts had died, and median OS from randomization was 17.9 months (95% CI, 14.9-31.2). Although ORR in this post-hoc, exploratory analysis is less than that observed in phase 3 trials of first-line BRAF +/- MEK inhibition, BRAF +/- MEK inhibition appears to have antitumor activity following pembro in pts with advanced BRAFV600-mutant melanoma, particularly in those without prior BRAF +/- MEK therapy.

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