Cyramza ® (ramucirumab)

För fullständig produktresumé för Cyramza® se FASS.

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Cyramza® (ramucirumab): Hypertoni

Avbryt behandling med ramucirumab permanent om medicinskt signifikant hypertoni inte kan kontrolleras med blodtryckssänkande behandling.

Management of hypertension

The blood pressure of patients should be monitored prior to each ramucirumab administration and treated as clinically indicated. Ramucirumab therapy should be temporarily discontinued in the event of severe hypertension, until controlled with medical management. If there is medically significant hypertension that cannot be controlled safely with antihypertensive therapy, ramucirumab therapy should be permanently discontinued.1

Incidence of Hypertension

Clinical Studies

The incidence of any grade and grade ≥3 hypertension in the phase 3 clinical studies is summarized in Table 1

Table 1. Incidence of Any Grade and Grade ≥3 Hypertension in the Phase 3 Clinical Studies2-7

 

Hypertensiona

Any Grade (%)

Grade ≥3 (%)

REGARD (second-line gastric cancer)

Ramucirumab (n=236)

16

8

Placebo (n=115)

8

3

RAINBOW (second-line gastric cancer)

Ramucirumab + Paclitaxel (n=327)

25

15

Paclitaxel + Placebo (n=329)

6

3

REVEL (second-line NSCLC)

Ramucirumab + Docetaxel (n=627)

11

6

Docetaxel + Placebo (n=618)

5

2

RAISE (second-line CRC)

Ramucirumab + FOLFIRI (n=529)

26

11

FOLFIRI + Placebo (n=528)

9

3

REACH-2 (second-line HCC)

Ramucirumab (n=197)

25

13

Placebo (n=95)

12

5

RELAY (first-line EGFR-mutation+ NSCLC)


Ramucirumab + Erlotinib (n=221)

46

24

Placebo + Erlotinib (n=225)

12

5

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

a Hypertension is the consolidated, MedDRA-preferred term.

Systematic Review and Meta-Analysis

A meta-analysis of all completed phase 3 studies and 5 meta-analyses combining eligible phase 2 and 3 studies evaluated the risk of hypertension associated with the use of ramucirumab for the treatment of patients with solid tumors.8-13 These analyses included between 6 and 11 studies that evaluated the use of ramucirumab in 1495 to 3103 patients. The incidence of all grade hypertension ranged from 10.8% to 40.5% of patients. Five analyses found that the risk of developing hypertension was greater in ramucirumab-treated patients with RR between 2.28 and 2.83 for all grade hypertension and RR between 3.58 and 3.73 for high-grade hypertension.8-11,13 One analysis also suggested that hypertension was frequently associated with ramucirumab therapy, with an OR of 3.60 for any grade of hypertension and 4.16 for grade 3-4 hypertension.12

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. 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

4. 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

5. 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

6. 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

7. 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

8. Wang J, Wang Z, Zhao Y. Incidence and risk of hypertension with ramucirumab in cancer patients: a meta-analysis of published studies. Clin Drug Investig. 2015;35(4):221-228. http://dx.doi.org/10.1007/s40261-015-0272-z.

9. 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.

10. Qi WX, Fu S, Zhang Q, Guo XM. Incidence and risk of hypertension associated with ramucirumab in cancer patients: a systematic review and meta-analysis. J Cancer Res Ther. 2016;12(2):775-781. http://dx.doi.org/10.4103/0973-1482.148700

11. Wang K, Qu X, Wang Y, et al. The impact of ramucirumab on survival in patients with advanced solid tumors: a systematic review and meta-analysis of randomized II/III controlled trials. Clin Drug Investig. 2016;36(1):27-39. https://doi.org/10.1007/s40261-015-0355-x

12. Roviello G, Pacifico C, Corona P, Generali D. Risk of hypertension with ramucirumab-based therapy in solid tumors: data from a literature based meta-analysis. Invest New Drugs. 2017;35(4):518-523. https://doi.org/10.1007/s10637-017-0452-1

13. Arnold D, Fuchs CS, Tabernero J, et al. Meta-analysis of individual patient safety data from six randomized, placebo-controlled trials with the antiangiogenic VEGFR2-binding monoclonal antibody ramucirumab. Ann Oncol. 2017;28(12):2932-2942. https://doi.org/10.1093/annonc/mdx514

Glossary

CRC = colorectal cancer

FOLFIRI = irinotecan, folinic acid, and 5-fluorouracil

NSCLC = non-small cell lung cancer

OR = odds ratio

RR = relative risk

Datum fӧr senaste ӧversyn 2019 M07 11

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