Melanoma: BRIM-3 trial

Abbreviations

No EU-CTR

  • BRIM-3 references
    2011-06-30
    Paul B. Chapman
    Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation
Investigated (inv)
Comparator (comp)

VEMR

daca

337

338

Phase:

3

Randomisation:

Open label

Primary tumour:

Melanoma

Subtype (biomarker):

V600E MT

Stage:

meta

Line of therapy:

L1

Primary
VEMR
daca
HR
p
OS @6mo
84%
64%
0.37 (0.26-0.55)
<0.001
PFS
5.3 mo
1.6 mo
0.26 (0.20-0.33)
<0.001
Secondaries
VEMR
daca
HR
p
ORR
48%
5%
<0.001
(all grades, %)
VEMR
daca
p
Arthralgia
21
<2
NA
Rash
18
0
NA
Cutaneous squamous-cell carcinoma
12
<1
NA
Keratoacanthoma
8
0
NA
Nausea
8
13
NA
Pruritus
7
0
NA
Hyperkeratosis
6
0
NA
Diarrhea
6
<2
NA
Vomiting
4
6
NA
Neutropenia
<2
10
NA
  • Inclusion
  • Exclusion

- adults, ≥18 years of age - metastatic melanoma, stage IIIC or IV (AJCC) - treatment-naïve (no prior systemic anticancer therapy) - positive for BRAF V600E mutation - measurable disease by RECIST criteria - negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion.

- active central nervous system metastases - history of carcinomatous meningitis - severe cardiovascular disease within 6 months prior to study drug administration - previous malignancy within 5 years prior to study, except for basal or squamous cell carcinoma of the skin, melanoma in-situ, or carcinoma in-situ of the cervix.

Characteristics
VEMR
daca
Agedc-comma sexdc-comma race
Median age (range)dc-comma yr
56 (21–86)
52 (17–86)
Male - no.(%)
200 (59)
181 (54)
White race - no.(%)
333 (99)
338 (100)
Geographic region - no.(%)
Australia or New Zealand
39 (12)
38 (11)
North America
86 (26)
86 (25)
Western Europe
205 (61)
203 (60)
Other
7 (2)
11 (3)
ECOG - no.(%)
0
229 (68)
230 (68)
1
108 (32)
108 (32)
Extent of metastatic melanoma - no.(%)
M1c
221 (66)
220 (65)
M1b
62 (18)
65 (19)
M1a
34 (10)
40 (12)
Unresectable IIIC
20 (6)
13 (4)
LDH level - no.(%)
≤ULN
142 (42)
142 (42)
>ULN
195 (58)
196 (58)
Ad-hoc:
no.pts inv.
no.pts comp.
VEMR
daca
HR
p
  • OS @6mo
  • PFS
analisys of OS @6mo
VEMR
daca
HR (95% CI)
Age
< 65 yr
0.40 (0.25–0.62)
≥65 yr
0.33 (0.16–0.67)
Sex
Female
0.49 (0.28–0.86)
Male
0.30 (0.18–0.51)
ECOG
0
0.31 (0.18–0.54)
1
0.42 (0.25–0.72)
Disease stage
IIIC
0.53 (0.07–3.76)
M1a
0.31 (0.07–1.47)
Disease stage
M1b
0.91 (0.33–2.52)
M1c
0.32 (0.21–0.50)
Disease stage
IIICdc-comma M1adc-comma or M1b
0.64 (0.29–1.38)
LDH level
Normal
0.37 (0.19–0.69)
Elevated
0.36 (0.22–0.57)
Region
North America
0.44 (0.20–0.93)
Western Europe
0.33 (0.20–0.53)
Region
Australia or New Zealand
0.59 (0.20–1.78)
analisys of PFS
VEMR
daca
HR (95% CI)
Age
<65 yr
0.26 (0.20–0.34)
≥65 yr
0.26 (0.15–0.45)
Sex
Female
0.26 (0.18–0.38)
Male
0.25 (0.18–0.34)
ECOG
0
0.21 (0.15–0.29)
1
0.34 (0.23–0.51)
Disease stage
IIIC
0.06 (0.01–0.54)
M1A
0.23 (0.08–0.63)
Disease stage
M1B
0.34 (0.19–0.59)
M1C
0.24 (0.18–0.32)
Disease stage
IIICdc-comma M1A or M1B
0.31 (0.20–0.48)
LDH level
Normal
0.22 (0.15–0.31)
Elevated
0.28 (0.20–0.39)
Region
North America
0.30 (0.19–0.47)
Western Europe
0.24 (0.17–0.32)
Region
Australia or New Zealand
0.28 (0.13–0.61)