Melanoma: COMBI-v trial

Abbreviations

No EU-CTR

  • COMBI-v references
    2015-01-01
    C. Robert
    Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib
Investigated (inv)
Comparator (comp)

DABR+TRAM

VEMR

352

352

Phase:

3

Randomisation:

Open label

Primary tumour:

Melanoma

Subtype (biomarker):

V600E MT, V600K MT

Stage:

meta

Line of therapy:

L1

Primary
DABR+TRAM
VEMR
HR
p
OS @1yr
72%
65%
0.69 (0.53-0.89)
0.005
PFS
Secondaries
DABR+TRAM
VEMR
HR
p
PFS
11.4 mo
7.3 mo
0.56 (0.46-0.69)
<0.001
ORR
64%
51%
<0.001
CR
13%
8%
DoR
13.8 mo
7.5 mo
(all grades, %)
DABR+TRAM
VEMR
p
Pyrexia
53
21
NA
Nausea
35
36
NA
Diarrhea
32
38
NA
Vomiting
29
15
NA
Rash
22
43
NA
Hand–foot syndrome
4
25
NA
Hyperkeratosis
4
25
NA
Skin papilloma
2
23
NA
Cutaneous squamous-cell carcinoma
1
18
NA
Dermatitis acneiform
6
6
NA
Chills
31
8
NA
Arthralgia
24
51
NA
  • Inclusion
  • Exclusion

- Age ≥18 years - Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma - Measurable disease according to RECIST 1.1 - Women of childbearing potential with negative serum pregnancy test prior to randomisation - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Adequate baseline organ function.

- Any prior use of a BRAF or MEK inhibitor - Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed - History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer) - Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed) - Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for ≥12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for ≥12 weeks, and are asymptomatic with no corticosteroid requirements for ≥4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for >= 4 weeks prior to randomisation - History or evidence of cardiovascular risk (LVEF < LLN; QTcB ≥480 msec; blood pressure or systolic ≥140 mmHg or diastolic ≥90 mmHg which cannot be controlled by anti-hypertensive therapy) - History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR).

Characteristics
DABR+TRAM
VEMR
Agedc-comma sexdc-comma previous immunotherapy
Median age (range) yr
55 (18–91)
54 (18–88)
Male - no.(%)
208 (59)
180 (51)
Previous immunotherapy - no.(%)
61 (17)
93 (26)
ECOG - no.(%)
0
248 (71)
248 (70)
1
102 (29)
104 (30)
BRAF mutation - no.(%)
V600E
312 (90)
317 (90)
V600K
34 (10)
34 (10)
Tumor stage at screening - no.(%)
IVM1c
221 (63)
208 (59)
IIIcdc-comma IVM1adc-comma or IVM1b
130 (37)
143 (41)
Metastasis stage at screening - no.(%)
M0
14 (4)
26 (7)
M1a
55 (16)
50 (14)
M1b
61 (17)
67 (19)
M1c
221 (63)
208 (59)
Baseline LDH - no.(%)
>ULN
118 (34)
114 (32)
≤ULN
233 (66)
238 (68)
Visceral disease at baseline - no.(%)
Yes
278 (79)
271 (77)
No
73 (21)
81 (23)
No. of disease sites at baseline - no.(%)
<3
177 (50)
201 (57)
≥3
174 (50)
151 (43)
Ad-hoc:
no.pts inv.
no.pts comp.
DABR+TRAM
VEMR
HR
p
  • OS @1yr
  • PFS
analisys of OS @1yr
DABR+TRAM
VEMR
HR (95% CI)
Age (*=the upper limit of 95%CI≥1)
<65 yr
0.74*
≥65 yr
0.61*
Sex
Male
0.87*
Female
0.46
BRAF mutation
V600K
0.85*
V600E
0.70
Tumor stage
IIIcdc-comma IVM1adc-comma or IVM1b
0.40
IVM1c
0.77*
Baseline LDH
≤ULN
0.58
>ULN
0.78*
No. of disease sites
≤2
0.59
≥3
0.68
Baseline ECOG
0
0.53
1
1.03*
analisys of PFS
DABR+TRAM
VEMR
HR (95% CI)
Age (*=the upper limit of 95%CI≥1)
<65 yr
0.57
≥65 yr
0.50
Sex
Male
0.65
Female
0.44
BRAF mutation
V600K
0.71*
V600E
0.56
Tumor stage
IIIcdc-comma IVM1adc-comma or IVM1b
0.39
IVM1c
0.63
Baseline LDH
≤ULN
0.46
>ULN
0.72*
No. of disease sites
≤2
0.49
≥3
0.57
Baseline ECOG
0
0.50
1
0.75*