Established Safety Profile

The safety of YONDELIS® was evaluated in 755 patients

YONDELIS® was studied in 6 open-label, single-arm trials, in which 377 patients received YONDELIS®, and 1 open-label, randomized, active-controlled clinical trial, in which 378 patients received YONDELIS®. In these trials, 26% (197) of patients were treated with YONDELIS® for 6 months or longer, and 8% (57) were treated with YONDELIS® for 1 year or longer.1

 

Incidence of selected treatment-emergent laboratory abnormalities in a pivotal trial*1

 

Laboratory Abnormalities

YONDELIS®

All Grades (%)

Grades 3-4 (%)

Chemistry

Increased ALT

90

31

Increased AST

84

17

Increased alkaline phosphatase

70

1.6

Hypoalbuminemia

63

3.7

Increased creatinine

46

4.2

Increased creatine phosphokinase

33

6.4

Hyperbilirubinemia

13

1.9

Hematology

Anemia

96

19

Neutropenia

66

43

Thrombocytopenia

59

21

Laboratory Abnormalities

Dacarbazine

All Grades (%)

Grades 3-4 (%)

Chemistry

Increased ALT

33

0.6

Increased AST

32

1.2

Increased alkaline phosphatase

60

0.6

Hypoalbuminemia

51

3.0

Increased creatinine

29

1.2

Increased creatine phosphokinase

9

0.6

Hyperbilirubinemia

5

0.6

Hematology

Anemia

79

12

Neutropenia

47

26

Thrombocytopenia

57

20

 
 

ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CPK = creatine phosphokinase.

*Treatment-emergent laboratory abnormalities included those higher in the trabectedin arm compared with the dacarbazine arm by ≥5% (all grades) or by ≥2% (Grades 3-4). Incidence based on number of patients who had both baseline and at least 1 on-study laboratory measurement.

YONDELIS® group (range: 373 to 377 patients) and dacarbazine group (range: 166 to168 patients).

Adverse reactions reported in the pivotal trial

 

Selected adverse reactions occurring in ≥10% of patients receiving YONDELIS® and at a higher incidence than in the control arm in the pivotal trial‡1

System Organ Class

YONDELIS® (N=378)

Adverse Reaction

All Gradesb (%)

Grades 3-4 (%)

Gastrointestinal disorders

Nausea

75

7

Vomiting

46

6

Constipation

37

0.8

Diarrhea

35

1.6

General disorders and administration site conditions

Fatigue§

69

8

Peripheral edema

28

0.8

Metabolism and nutrition disorders

Decreased appetite

37

1.9

Respiratory, thoracic, and mediastinal disorders

Dyspnea

25

4.2

Nervous system disorders

Headache

25

0.3

Musculoskeletal and connective tissue disorders

Arthralgia

15

0

Myalgia

12

0

Psychiatric disorders

Insomnia

15

0.3

System Organ Class

Dacarbazine (N=172)

Adverse Reaction

All Grades (%)

Grades 3-4 (%)

Gastrointestinal disorders

Nausea

50

1.7

Vomiting

22

1.2

Constipation

31

0.6

Diarrhea

23

0

General disorders and administration site conditions

Fatigue§

52

1.7

Peripheral edema

13

0.6

Metabolism and nutrition disorders

Decreased appetite

21

0.6

Respiratory, thoracic and mediastinal disorders

Dyspnea

20

1.2

Nervous system disorders

Headache

19

0

Musculoskeletal and connective tissue disorders

Arthralgia

8

1.2

Myalgia

6

0

Psychiatric disorders

Insomnia

9

0

 
 

†Limited to adverse reactions occurring at a rate of ≥10% in the trabectedin arm and at a rate higher in the trabectedin arm compared with the dacarbazine arm by ≥5% in overall incidence or by ≥2% for Grades 3-4 adverse reactions.

‡Toxicity grade is based on National Cancer Institute common toxicity criteria, version 4.0.

§Fatigue is a composite of the following adverse event terms: fatigue, asthenia, and malaise.

 

Reference:

  1. YONDELIS® (trabectedin) [package insert]. Horsham, PA: Janssen Products, LP; 2017.