Details of data from Melanoma clinical trials

Investigated (inv)

Comparator (comp)

IPI+DACA

PLB+DACA

250

252

Phase:

3

Randomisation:

Double blind

Primary tumour:

Melanoma

Subtype (biomarker):

Any

Stage:

Line of therapy:

L1

Primary

IPI+DACA

PLB+DACA

HR

p

OS

11.2 mo

9.1 mo

0.72 (0.59-0.87)

<0.001

—

Secondaries

IPI+DACA

PLB+DACA

HR

p

PFS

—

0.76 (0.63-0.93)

0.006 ORR

15.2%

10.3%

—

0.09 Disease control

33.2%

30.2%

—

0.41 DoR

19.3 mo

8.1 mo

—

0.03 (all grades, %)

IPI+DACA

PLB+DACA

p

Diarrhea

36.4

24.7 NA

Pyrexia

36.8

9.2 NA

Increase in ALT

33.2

5.6 NA

Pruritus

29.6

8.8 NA

Increase in AST

29.1

5.6 NA

Rash

24.7

6.8 NA

Chills

11.3

4 NA

Weight loss

10.9

5.2 NA

Colitis

4.5

0 NA

Hepatitis

1.6

0 NA

Vomiting

31.6

27.9 NA

Constipation

28.3

27.9 NA

Hypothyroidism

1.6

0.4 NA

Hyperthyroidism

0.4

0 NA

Inclusion
Exclusion

- Measurable Disease - Eastern Cooperative Oncology Group (ECOG) 0 or 1 - Lab / imaging requirements - Neg for Human Immunodeficiency Virus (HIV), Hepatitis B (HepB), C - Men and Women > 18 years (16 were allowable) - Prior therapy restriction (adjuvant only)

- Pregnant / nursing - Inadequate contraception - Brain metastasis - Primary ocular or mucosal melanoma

Characteristics

IPI+DACA

PLB+DACA

Age & sex

Mean agedc-comma yr

57.5

56.4 Maledc-comma no.

152 (60.8%)

149 (59.1%)

Femaledc-comma no.

98 (39.2%)

103 (40.9%)

—

ECOG PS

0 177 (70.8%)

179 (71.0%)

1 73 (29.2%)

73 (29.0%)

—

Metastasis stage

M0

6 (2.4%)

8 (3.2%)

M1a

37 (14.8%)

43 (17.1%)

M1b

64 (25.6%)

62 (24.6%)

M1c

143 (57.2%)

139 (55.2%)

Lactate dehydrogenase

≤ULN

157 (62.8%)

140 (55.6%)

>ULN

93 (37.2%)

110 (43.7%)

Unknown

0.0 2 (0.8%)

—

Prior adjuvant therapy

66 (26.4%)

67 (26.6%)

—

Ad-hoc:

no.pts inv.

no.pts comp.

IPI+DACA

PLB+DACA

HR

p

OS (@1yr)

—

47.3%

36.3%

—

OS (@2yr)

—

28.5%

17.9%

—

OS (@3yr)

—

20.8%

12.2%

—

OS
—

analisys of OS

IPI+DACA

PLB+DACA

HR (95% CI)

Age

< 65 yr

—

0.44 (0.25-0.74)

≥ 65 yr

—

0.81 (0.36-1.78)

Sex

Male

—

0.45 (0.25-0.79)

Female

—

0.71 (0.35-1.45)

Metastasis stage

M0

—

0.10 (0.00-3.98)

M1a

—

0.81 (0.23-2.82)

Metastasis stage

M1b

—

0.56 (0.23-1.38)

M1c

—

0.40 (0.22-0.71)

ECOG

0 —

—

0.54 (0.31-0.91)

1 —

—

0.47 (0.21-1.02)

Previous adjuvant therapy

None

—

0.62 (0.36-1.02)

Interferon

—

0.35 (0.13-0.60)

LDH > ULN

No

—

0.52 (0.28-0.95)

Yes

—

0.72 (0.37-1.38)

LDH >2x ULN

No

—

0.52 (0.32-0.87)

Yes

—

0.51 (0.16-1.66)

Age of women

<50 yr

—

0.28 (0.07-1.00)

≥50 yr

—

1.07 (0.47-2.51)

—

analisys of —

IPI+DACA

PLB+DACA

HR (95% CI)

—

Melanoma: CA184024 trial

EMA SPC links

2011-06-30

Caroline Robert

Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma

Investigated (inv)

Comparator (comp)

Randomisation:

Primary tumour:

Subtype (biomarker):

Stage:

Line of therapy:

Primary

IPI+DACA

PLB+DACA

HR

p

OS

11.2 mo

9.1 mo

0.72 (0.59-0.87)

<0.001

—

—

—

—

—

Secondaries

IPI+DACA

PLB+DACA

HR

p

PFS

—

—

0.76 (0.63-0.93)

0.006

ORR

15.2%

10.3%

—

0.09

Disease control

33.2%

30.2%

—

0.41

DoR

19.3 mo

8.1 mo

—

0.03

(all grades, %)

IPI+DACA

PLB+DACA

p

Diarrhea

36.4

24.7

NA

Pyrexia

36.8

9.2

NA

Increase in ALT

33.2

5.6

NA

Pruritus

29.6

8.8

NA

Increase in AST

29.1

5.6

NA

Rash

24.7

6.8

NA