Cyramza ® (ramucirumab)

För fullständig produktresumé för Cyramza® se FASS.

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Cyramza® (ramucirumab): Arteriella tromboemboliska händelser

Cyramza (ramucirumab) ska sättas ut permanent hos patienter som drabbas av en allvarlig arteriell tromboembolisk händelse (ATE).

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

Datum fӧr senaste ӧversyn 2019 M11 13


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