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) Thromboembolic Events

Ramucirumab should be permanently discontinued in patients who experience a severe arterial thromboembolic event.

Incidence of Thromboembolic Events

Clinical Studies

The incidence of any grade and grade ≥3 ATEs and VTEs in the phase 3 registration studies are summarized in Table 1 and Table 2.

Table 1. Incidence Rate of ATEs in the Phase 3 Clinical Studies1-6

 

Arterial Thromboembolisma

Any Grade (%)

Grade ≥3 (%)

REGARD (second-line gastric cancer)

Ramucirumab (n=236)

2

1

Placebo (n=115)

0

0

RAINBOW (second-line gastric cancer)

Ramucirumab + Paclitaxel (n=327)

2

1

Paclitaxel + Placebo (n=329)

2

1

REVEL (second-line NSCLC)

Ramucirumab + Docetaxel (n=627)

2

1

Docetaxel + Placebo (n=618)

2

1

RAISE (second-line CRC)

FOLFIRI + Ramucirumab (n=529)

2

1

FOLFIRI + Placebo (n=528)

3

1

REACH-2 (second-line HCC)

Ramucirumab (n=197)

3

2

Placebo (n=95)

1

1

RELAY (first-line EGFR mutation+ NSCLC)

Erlotinib + Ramucirumab (n=221)

1

1

Erlotinib + Placebo (n=225)

0

0

Abbreviations: ATEs = arterial thromboembolic events; CRC = colorectal cancer; EGFR = epidermal growth factor receptor; FOLFIRI = irinotecan, folinic acid, and 5-fluorouracil; HCC = hepatocellular carcinoma; MedDRA = Medical Dictionary for Regulatory Activities; NSCLC = non-small cell lung cancer.

a Arterial thromboembolism is the consolidated, MedDRA-preferred term.

Table 2. Incidence Rate of VTEs in the Phase 3 Clinical Studies1-6

 

Venous Thromboembolisma

Any Grade (%)

Grade ≥3 (%)

REGARD (second-line gastric cancer)

Ramucirumab (n=236)

4

1

Placebo (n=115)

7

4

RAINBOW (second-line gastric cancer)

Ramucirumab + Paclitaxel (n=327)

4

2

Paclitaxel + Placebo (n=329)

6

3

REVEL (second-line NSCLC)

Ramucirumab + Docetaxel (n=627)

3

2

Docetaxel + Placebo (n=618)

6

3

RAISE (second-line CRC)

FOLFIRI + Ramucirumab (n=529)

8

4

FOLFIRI + Placebo (n=528)

6

2

REACH-2 (second-line HCC)

Ramucirumab (n=197)

1

0

Placebo (n=95)

2

1

RELAY (first-line EGFR mutation+ NSCLC)

Erlotnib + Ramucirumab (n=221)

3

1

Erlotnib + Placebo (n=225)

4

2

Abbreviations: CRC = colorectal cancer; EGFR = epidermal growth factor receptor; FOLFIRI = irinotecan, folinic acid, and 5-fluorouracil; HCC = hepatocellular carcinoma; MedDRA = Medical Dictionary for Regulatory Activities; NSCLC = non-small cell lung cancer; VTE = venous thromboembolic events.

a Venous thromboembolism is the consolidated, MedDRA-preferred term.

Meta-Analysis

A systematic review and meta-analysis of eligible phase 2 and 3 studies was conducted to assess the risk of thromboembolic events associated with the use of ramucirumab for the treatment of patients with solid tumors (n=5694). Of the 11 studies that were included in the analysis, a total of 3101 patients received ramucirumab and were included in the incidence analysis. Seven studies reported ATEs and the incidence ranged from 1.1% to 10.4%. Eight studies reported VTEs and the incidence ranged from 1% to 13%. The relative risk of ATE and VTE was 0.97 (95% CI: 0.62-1.52; p=.91) and 0.83 (95% CI: 0.52-1.35; p=.46), respectively.7

Management of Thromboembolic Events

Permanently discontinue ramucirumab in patients who experience a severe ATE.8

References

1. 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

2. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384(9944):665-673. http://dx.doi.org/10.1016/S0140-6736(14)60845-X

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. Tabernero J, Yoshino T, Cohn AL, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015;16(5):499-508. http://dx.doi.org/10.1016/S1470-2045(15)70127-0

5. Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282-296. http://dx.doi.org/10.1016/S1470-2045(18)30937-9

6. Nakagawa K, Garon EB, Seto T, et al. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(12):1655-1669. https://doi.org/10.1016/S1470-2045(19)30634-5

7. Abdel-Rahman O, ElHalawani H. Risk of cardiovascular adverse events in patients with solid tumors treated with ramucirumab: a meta analysis and summary of other VEGF targeted agents. Crit Rev Oncol Hematol. 2016;102:89-100. http://dx.doi.org/10.1016/j.critrevonc.2016.04.003.

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

Glossary

ATE = arterial thromboembolic event

VTE = venous thromboembolic event

Date of Last Review: November 13, 2019

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