Cyramza ® (ramucirumab)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information. Please refer to the link for full prescribing information: Cyramza Summary of Product Characteristics (SmPC)

Cyramza® (ramucirumab): Safety in Patients with Gastric-GEJ Adenocarcinoma

In REGARD, the most common ARs in ramucirumab-treated patients were hypertension and diarrhea. In RAINBOW, they were fatigue, neutropenia, diarrhea, and epistaxis.

Information from Summary of Product Characteristics

Cyramza in combination with paclitaxel is indicated for the treatment of adult patients with advanced gastric cancer or gastro-oesophageal junction adenocarcinoma with disease progression after prior platinum and fluoropyrimidine chemotherapy.1

Cyramza monotherapy is indicated for the treatment of adult patients with advanced gastric cancer or gastro-oesophageal junction adenocarcinoma with disease progression after prior platinum or fluoropyrimidine chemotherapy, for whom treatment in combination with paclitaxel is not appropriate.1

Study Designs

The REGARD Study

The REGARD trial was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial in patients with metastatic or locally advanced gastric or GEJ adenocarcinoma treated previously with fluoropyrimidine- or platinum-based combination therapy with an ECOG PS of 0 or 1. Patients were randomly assigned in a 2:1 ratio (stratified by weight loss, region, and location of the primary tumor) to receive ramucirumab (8 mg/kg every 2 weeks) plus BSC (n=238) or placebo (every 2 weeks) plus BSC (n=117) until disease progression, unacceptable toxicity, withdrawal, or death.2

The RAINBOW Study

The RAINBOW trial was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial in patients with metastatic or locally advanced nonresectable gastric or GEJ adenocarcinoma following disease progression during or within 4 months after last dose of first-line platinum plus fluoropyrimidine combination chemotherapy with or without an anthracycline and an ECOG PS of 0 or 1. Patients were randomly assigned in a 1:1 ratio (stratified by region, measurable vs nonmeasurable disease, and TTP on first-line therapy) to receive ramucirumab (8 mg/kg days 1 and 15) plus paclitaxel (80 mg/m2 days 1, 8, and 15) (n=330) or placebo (days 1 and 15) plus paclitaxel (80 mg/m2 days 1, 8, and 15) (n=335) of a 28-day cycle until disease progression, unacceptable toxicity, withdrawal, or death.3

Safety

The REGARD Study

The frequency and severity of ARs that have been reported at an incidence rate of ≥5% in patients who received ramucirumab in the REGARD study are presented in Table 1.

Table 1. Adverse Reactions That Occurred at an Incidence Rate of ≥5% in Patients who Received Ramucirumab in the REGARD Trial2,4

Adverse Reactions (MedDRA) System Organ Class

All Grades
(Frequency %)

Grade 3-4
(Frequency %)

All Grades
(Frequency %)

Grade 3-4
(Frequency %)

Ramucirumab
(n=236)

Placebo
(n=115)

Gastrointestinal Disorders    

Abdominal paina

28.8

5.9

27.8

2.6

Diarrhea

14.4

0.8

8.7

1.7

Metabolism and Nutrition Disorders

Hypokalemia

5.9

2.1

5.2

0.9

Hyponatremia

5.5

3.4

1.7

0.9

Nervous System Disorders

Headache

9.3

0

3.5

0

Vascular Disorders

Hypertensionb

16.1

7.6

7.8

2.6

Abbreviation: MedDRA = Medical Dictionary for Regulatory Activities. 

a Includes hepatic pain.

b MedDRA-preferred terms included are blood pressure increased and hypertension.

Clinically relevant ADRs reported in ≥1% and <5% of the ramucirumab-treated patients in the REGARD trial were

  • neutropenia

  • ATEs

  • intestinal obstruction

  • epistaxis, and

  • rash.4

The RAINBOW Study

The frequency and severity of ARs that have been reported at an incidence rate of ≥5% in patients who received ramucirumab in combination with paclitaxel in the RAINBOW study are presented in Table 2.

Table 2. Adverse Reactions That Occurred at an Incidence Rate of ≥5% in Patients who Received Ramucirumab in Combination With Paclitaxel in the RAINBOW Trial4 

Adverse Reactions (MedDRA) System Organ Class

All Grades
(Frequency %)

Grade ≥3
(Frequency %)

All Grades
(Frequency %)

Grade ≥3
(Frequency %)

Ramucirumab + Paclitaxel
(n=327)

Placebo + Paclitaxel
(n=329)

Blood and Lymphatic System Disorders     

Leukopenia

33.9

17.4

21.0

6.7

Neutropenia

54.4

40.7

31.0

18.8

Thrombocytopenia

13.1

1.5

6.1

1.8

Gastrointestinal disorders    

Diarrhea

32.4

3.7

23.1

1.5

Gastrointestinal hemorrhage eventsa

10.1

3.7

6.1

1.5

Stomatitis

19.6

0.6

7.3

0.6

General Disorders and Administration-Site Disorders    

Fatigue/Asthenia

56.9

11.9

43.8

5.5

Peripheral edema

25.1

1.5

13.7

0.6

Metabolism and Nutrition Disorders    

Hypoalbuminemia

11.0

1.2

4.9

0.9

Renal and Urinary Disorders    

Proteinuria

16.8

1.2

6.1

0

Respiratory, Thoracic, and Mediastinal Disorders    

Epistaxis

30.6

0

7.0

0

Vascular Disorders    

Hypertensionb

25.1

14.7

5.8

2.7

Abbreviation: MedDRA = Medical Dictionary for Regulatory Activities. 

a MedDRA preferred terms included anal hemorrhage, diarrhea hemorrhage, gastric hemorrhage, gastrointestinal hemorrhage, hematemesis, hematochezia, hemorrhoidal hemorrhage, Mallory-Weiss syndrome, melena, esophageal hemorrhage, rectal hemorrhage, and upper gastrointestinal hemorrhage.

b Includes hypertensive cardiomyopathy.

Clinically relevant ADRs reported in ≥1% and <5% of the ramucirumab plus paclitaxel-treated patients in the RAINBOW trial were

  • GI perforation (1.2% for ramucirumab plus paclitaxel vs 0.3% for placebo plus paclitaxel) and

  • sepsis (3.1% for ramucirumab plus paclitaxel vs 1.8% for placebo plus paclitaxel).4

References

1. Cyramza [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2. Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31-39. http://dx.doi.org/10.1016/S0140-6736(13)61719-5

3. Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224-1235. http://dx.doi.org/10.1016/S1470-2045(14)70420-6

4. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

Glossary

ADR = adverse drug reaction

AR = adverse reaction

ATE = arterial thromboembolic event

ECOG = Eastern Cooperative Oncology Group

GEJ = gastroesophageal junction

GI = gastrointestinal

PS = performance status

Date of Last Review: January 02, 2020

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