Melanoma: NA trial
Melanoma: NA trial
Melanoma: NA trial

Abbreviations

No EU-CTR

  • NA references
    2013-06-20
    Alice T. Shaw
    Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer
Investigated (inv)
Comparator (comp)

CRIZ

chemo

173

174

Phase:

3

Randomisation:

Open label

Primary tumour:

NSCLC

Subtype (biomarker):

ALK poz.

Stage:

meta

Line of therapy:

L2

Primary
CRIZ
chemo
HR
p
PFS
7.7 mo
3.0 mo
0.49 (0.37-0.64)
<0.001
Secondaries
CRIZ
chemo
HR
p
ORR
65%
20%
na
<0.001
OS interim
na
na
1.02 (0.68-1.54)
0.54
DoR
31.1 mo
24.4 mo
Time to response
6.3 mo
12.6 mo
(all grades, %)
CRIZ
chemo
p
Vision disorder
60
9
NA
Diarrhea
60
19
NA
Nausea
55
37
NA
Vomiting
47
18
NA
Constipation
42
23
NA
AST increased
38
15
NA
Edema
31
16
NA
Upper respiratory infection
26
13
NA
Dysgeusia
26
9
NA
Rash
9
17
NA
  • Inclusion
  • Exclusion

- histologically or cytologically proven diagnosis of non-small cell lung cancer - positive for the ALK fusion gene (test provided by a central laboratory) - must have had disease progression after only one prior chemotherapy and that regimen but must have included one platinum drug - tumors must be measurable

- prior treatment with crizotinib (PF-02341066) - current treatment in another clinical trial

Characteristics
CRIZ
chemo
Agedc-comma sex
Median age (range) yr
51 (22-81)
49 (24-85)
<65 yr
146 (84)
151 (87)
≥65 yr
27 (16)
23 (13)
Male - no.(%)
75 (43)
78 (45)
Race - no.(%)
White
90 (52)
91 (52)
Asian
79 (46)
78 (45)
Other
4 (2)
5 (3)
Smoking status - no.(%)
Never
108 (62)
111 (64)
Former
59 (34)
54 (31)
Current
5 (3)
9 (5)
Tumor histologic type - no.(%)
Adenocarcinoma
164 (95)
164 (94)
Non-adenocarcinoma
5 (3)
7 (4)
ECOG performance status - no.(%)
0
72 (42)
65 (37)
1
84 (49)
95 (55)
2
16 (9)
14 (8)
Extent of disease - no.(%)
Locally advanced
7 (4)
16 (9)
Metastatic
165 (95)
158 (91)
Brain metastases - no.(%)
Presence of brain metastases
60 (35)
60 (34)
Ad-hoc:
no.pts inv.
no.pts comp.
CRIZ
chemo
HR
p
  • PFS
analisys of PFS
CRIZ
chemo
HR (95% CI)
Age (n)
<65 yr (297)
0.49 (0.37-0.65)
≥65 yr (50)
0.54 (0.27-1.08)
Race (n)
Non-Asian (190)
0.45 (0.30-0.66)
Asian (157)
0.53 (0.36-0.76)
Smoking status (n)
Non-smoker (219)
0.45 (0.32-0.63)
Smoker or ex-smoker (127)
0.53 (0.34-0.83)
Tumor histologic type (n)
Adenocarcinoma (328)
0.50 (0.38-0.66)
Non-adenocarcinoma (12)
0.12 (0.01-1.02)
ECOG (n)
0 or 1 (313)
0.48 (0.36-0.63)
2 (34)
0.31 (0.12-0.86)
Brain metastases (n)
Present (120)
0.67 (0.44-1.03)
Absent (227)
0.43 (0.30-0.60)
Prior EGFR TKI therapy (n)
Yes (41)
0.48 (0.22-1.03)
No (306)
0.49 (0.37-0.66)
analisys of
CRIZ
chemo
HR (95% CI)

2007-001974-10

  • NA references
    2016-11-10
    A.M.M. Eggermont
    Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy
Investigated (inv)
Comparator (comp)

IPIL

PLB

475

476

Phase:

3

Randomisation:

Double blind

Primary tumour:

Melanoma

Subtype (biomarker):

Any

Stage:

early

Line of therapy:

ADJ

Primary
IPIL
PLB
HR
p
RFS @5yr
40.8%
30.3%
0.76 (0.64-0.89)
<0.001
OS @5yr
65.4%
54.4%
0.72 (0.58–0.88)
0.001
Secondaries
IPIL
PLB
HR
p
RFS
27.6 mo
17.1 mo
0.77 (0.65-0.91)
0.002
dMFS @5yr
48.3%
38.9%
0.76 (0.64-0.92)
0.002
dMFS
48.3 mo
27.5 mo
(all grades, %)
IPIL
PLB
p
Discontinued treatment due to AE
53.3%
4.6%
NA
Any immune-related AE
90.4
39.7
NA
Any dermatologic AE
63.3
20.9
NA
Any gastrointestinal event
46.1
17.9
NA
Diarrhea
41.2
16.9
NA
Colitis
15.5
1.5
NA
Any endocrine-system event
37.8
8.0
NA
Hypophysitis
16.3
0.2
NA
Any hepatic event
24.4
4.2
NA
Any neurologic event
4.5
1.9
NA
  • Inclusion
  • Exclusion

- Age ≥18 years - Complete and adequate resection of Stage III melanoma with histologically confirmed melanoma metastatic to lymph node - Disease-free - Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 - Randomization within 12 weeks of surgery.

- Prior therapy for melanoma except surgery - Auto-immune disease.

Characteristics
IPIL
PLB
Agedc-comma sex
Median age (range)dc-comma yr
51 (20–84)
52 (18–78)
<50 yr
214 (45.1)
211 (44.3)
51 to <65 yr
180 (37.9)
178 (37.4)
Male - no.(%)
296 (62.3)
293 (61.6)
Disease stage (AJCC 2002) - no.(%)
IIIA
98 (20.6
88 (18.5)
IIIB
213 (44.8)
207 (43.5)
IIIC with 1–3 positive lymph nodes
69 (14.5)
83 (17.4)
IIIC with ≥4 positive lymph nodes
95 (20.0)
98 (20.6)
Type of lymph-node involvement - no.(%)
Microscopic
210 (44.2)
193 (40.5)
Macroscopic
265 (55.8)
283 (59.5)
No. of positive lymph nodes on pathological testing - no.(%)
1
217 (45.7)
220 (46.2)
2 or 3
163 (34.3)
158 (33.2)
≥4
95 (20.0)
98 (20.6)
Ulceration - no.(%)
Yes
197 (41.5)
203 (42.6)
No
257 (54.1)
244 (51.3)
Unknown
21 (4.4)
29 (6.1)
Ad-hoc:
no.pts inv.
no.pts comp.
IPIL
PLB
HR
p
  • RFS @5yr
  • OS @5yr
analisys of RFS @5yr
IPIL
PLB
HR (95% CI)
Disease stage
IIIA
0.98 (0.46–2.09)
IIIB
0.75 (0.50–1.14)
Disease stage
IIIC with 1–3 positive lymph nodes
1.00 (0.56–1.80)
IIIC with ≥4 positive lymph nodes
0.48 (0.28–0.81)
No. of positive lymph nodes
1
0.79 (0.52–1.21)
2 or 3
0.83 (0.53–1.30)
Type of positive lymph node
Microscopic
0.61 (0.39–0.96)
Macroscopic
0.80 (0.58–1.11)
Ulceration
Yes
0.64 (0.44–0.94)
No
0.80 (0.54–1.20)
Lymph-node and ulceration status
Microscopic and ulceration
0.54 (0.29–0.99)
Macroscopic and ulceration
0.76 (0.46–1.23)
Lymph-node and ulceration status
Microscopic and no ulceration
0.62 (0.30–1.29)
Macroscopic and no ulceration
0.90 (0.56–1.45)
No. of positive lymph nodes
≥4
0.48 (0.28–0.81)
analisys of OS @5yr
IPIL
PLB
HR (95% CI)
Disease stage
IIIA
0.98 (0.46-2.09)
IIIB
0.75 (0.50-1.14)
Disease stage
IIIC with 1–3 positive lymph nodes
1.00 (0.56-1.80)
IIIC with ≥4 positive lymph nodes
0.48 (0.28-0.81)
No. of positive lymph nodes
1
0.79 (0.52-1.21)
2 or 3
0.83 (0.53-1.30)
Type of positive lymph node
Microscopic
0.61 (0.39-0.96)
Macroscopic
0.80 (0.58-1.11)
Ulceration
Yes
0.64 (0.44-0.94)
No
0.80 (0.54-1.20)
Lymph-node and ulceration status
Microscopic and ulceration
0.54 (0.29-0.99)
Macroscopic and ulceration
0.76 (0.46-1.23)
Lymph-node and ulceration status
Microscopic and no ulceration
0.62 (0.30-1.29)
Macroscopic and no ulceration
0.90 (0.56-1.45)
No. of positive lymph nodes
≥4
0.48 (0.28-0.81)

No EU-CTR

  • NA references
    2012-02-23
    Jeffrey A. Sosman
    Survival in BRAF V600–Mutant Advanced Melanoma Treated with Vemurafenib
Investigated (inv)
Comparator (comp)

VEMR

NA

132

NA

Phase:

2

Randomisation:

Open label

Primary tumour:

Melanoma

Subtype (biomarker):

V600E MT

Stage:

meta

Line of therapy:

L2

Primary
VEMR
NA
HR
p
ORR @12,9mo.
53%
44-62
Secondaries
VEMR
NA
HR
p
PFS
6.8 mo
5.6-8.1
CR
6%
OS
15.9 mo
11.6-18.3
DoR
6.7 mo
5.6-8.6
(all grades, %)
VEMR
NA
p
Arthralgia
59
NA
Rash
52
NA
Photosensitivity reaction
52
NA
Fatigue
42
NA
Pruritus
29
NA
Skin papilloma
29
NA
Cutaneous squamous-cell carcinomaor keratoacanthoma
26
NA
Nausea
23
NA
Elevated liver enzymes
17
NA
Peripheral neuropathy
10
NA
PPE
10
NA
Facial palsy
2
NA
Hyperuricemia
2
NA
Delirium
1
NA
  • Inclusion
  • Exclusion

- adult patients >/=18 years of age - histologically confirmed metastatic melanoma (Stage IV, AJCC) - patients must have completed and failed at least one prior standard of care regimen (e.g. DTIC, temozolomide, etc.) - BRAF V600E positive mutation (by Roche CoDx BRAF mutation assay) - 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 CNS metastases on CT/MRI within 28 days prior to enrollment - history of or known carcinomatous meningitis - previous treatment with BRAF (sorafenib allowed) or MEK inhibitor - cardiac dysrhythmias >2 NCI CTCAE or treatment with drugs with dysrhythmic potential - uncontrolled hypertension(>150/100mmHg) despite optimal medical therapy - infectious disease including HIV, HBV and HCV.

Characteristics
VEMR
NA
Agedc-comma sex
Mediandc-comma yr
51.5
<65 yr
81%
≥65 yr
19%
Male
61%
Race or ethnic group - no.(%)
White
130 (98)
Hispanic
2 (2)
No. of prior therapies - no.(%)
1
67 (51)
2
36 (27)
≥3
29 (22)
Previous interleukin-2 - no.(%)
No
81 (61)
Yes
51 (39)
Previous ipilimumab - no.(%)
Yes
7 (5)
No
125 (95)
ECOG status score - no.(%)
0
61 (46)
1
71 (54)
Metastatic stage at diagnosis - no.(%)
M1a
33 (25)
M1b
18 (14)
M1c
81 (61)
Serum LDH - no.(%)
Normal
67 (51)
Elevated
65 (49)
BRAF mutation
BRAF V600E - no.
122
BRAF V600K - no.
10
Ad-hoc:
no.pts inv.
no.pts comp.
VEMR
NA
HR
p
  • ORR @12,9mo.
analisys of ORR @12,9mo.
VEMR
NA
HR (95% CI)
Age
<65 yr (n=107)
50%
≥65 yr (n=25)
64%
LDH at enrolment
Normal (n=67)
67%
>1.5x ULN (n=46)
33%
ECOG
0 (n=61)
56%
1 (n=71)
51%
Metastatic stage
M1a/M1b (n=51)
65%
M1c (n=80)
45%
No. of prior therapies
1 (n=67)
51%
>1 (n=65)
55%
Previous IL-2
Yes (n=51)
51%
No (n=81)
54%
Sex
Male (81)
53%
Female (51)
53%
analisys of
VEMR
NA
HR (95% CI)