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Cancer Chemotherapy and Pharmacology

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Open Access 01-05-2021 | Ramucirumab | Original Article

Evaluating clinical impact of a shortened infusion duration for ramucirumab: a model-based approach

Authors: Ling Gao, Yiu-Keung Lau, Ran Wei, Lisa O’Brien, Amanda Long, Yongzhe Piao, Paolo Abada

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2021

Abstract

Purpose

We investigated the impact of infusion duration (30 and 60 min) on the pharmacokinetic profile of ramucirumab using a population pharmacokinetic (PopPK) modeling approach. We also assessed the relationship between infusion rate and incidence of immediate infusion-related reactions (IRRs; occurring on the day of administration) using ramucirumab phase II/III study data.

Methods

The impact of different infusion durations (30 vs. 60 min) on the time-course of ramucirumab concentration profiles were evaluated using a PopPK model, established using ramucirumab pharmacokinetic data from 2522 patients. Logistic regression was used to evaluate the association between ramucirumab infusion rate and incidence of immediate IRRs in clinical trials.

Results

Ramucirumab time-course concentration profiles were equivalent following a 30- or 60-min infusion. In the pooled clinical study dataset, 254 of 3216 (7.9%) patients receiving ramucirumab experienced at least one immediate IRR (any grade). When grouped according to infusion rate quartile, the incidence of immediate IRRs (any grade or grade ≥ 3) was similar across quartiles; findings were confirmed in sensitivity analyses. The risk of immediate IRRs was not found to be associated with infusion rate based on multivariate logistic analysis.

Conclusion

Shortening the infusion duration of ramucirumab from 60 to 30 min has no impact on ramucirumab exposure. Analysis of trial data found no relationship between an increased risk of immediate IRRs and a faster infusion rate. Such a change in infusion duration is unlikely to affect the clinical efficacy or overall safety profile of ramucirumab.

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Chern B, Joseph D, Joshua D, Pittman K, Richardson G, Schou M, Lowe S, Copeman M, De Abreu LR, Lynch K (2004) Bisphosphonate infusions: patient preference, safety and clinic use. Support Care Cancer 12(6):463–466. https://doi.org/10.1007/s00520-004-0628-zCrossRefPubMed

Chiang J, Chan A, Shih V, Hee SW, Tao M, Lim ST (2010) A prospective study to evaluate the feasibility and economic benefits of rapid infusion rituximab at an Asian cancer center. Int J Hematol 91(5):826–830. https://doi.org/10.1007/s12185-010-0583-zCrossRefPubMed

Dranitsaris G, Yu B, Wang L, Sun W, Zhou Y, King J, Kaura S, Zhang A, Yuan P (2016) Abraxane(R) versus Taxol(R) for patients with advanced breast cancer: a prospective time and motion analysis from a Chinese health care perspective. J Oncol Pharm Pract 22(2):205–211. https://doi.org/10.1177/1078155214556008CrossRefPubMed

Lilly Cyramza prescribing information [online]. http://pi.lilly.com/us/cyramza-pi.pdf. Accessed 5 Dec 2019

Cohn AL, Yoshino T, Heinemann V, Obermannova R, Bodoky G, Prausova J, Garcia-Carbonero R, Ciuleanu T, Garcia-Alfonso P, Portnoy DC, Van Cutsem E, Yamazaki K, Clingan PR, Polikoff J, Lonardi S, O’Brien LM, Gao L, Yang L, Ferry D, Nasroulah F, Tabernero J (2017) Exposure–response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial. Cancer Chemother Pharmacol 80(3):599–608. https://doi.org/10.1007/s00280-017-3380-zCrossRefPubMedPubMedCentral

Tabernero J, Ohtsu A, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Ajani JA, Tomasek J, Safran H, Chandrawansa K, Hsu Y, Heathman M, Khan A, Ni L, Melemed AS, Gao L, Ferry D, Fuchs CS (2017) Exposure-response analyses of ramucirumab from two randomized, Phase III trials of second-line treatment for advanced gastric or gastroesophageal junction cancer. Mol Cancer Ther 16(10):2215–2222. https://doi.org/10.1158/1535-7163.MCT-16-0895CrossRefPubMed

Sheiner LB, Ludden TM (1992) Population pharmacokinetics/dynamics. Annu Rev Pharmacol Toxicol 32:185–209. https://doi.org/10.1146/annurev.pa.32.040192.001153CrossRef

Mould DR, Upton RN (2012) Basic concepts in population modeling, simulation, and model-based drug development. CPT Pharmacometr Syst Pharmacol 1:e6. https://doi.org/10.1038/psp.2012.4CrossRef

O’Brien L, Westwood P, Gao L, Heathman M (2017) Population pharmacokinetic meta-analysis of ramucirumab in cancer patients. Br J Clin Pharmacol 83(12):2741–2751. https://doi.org/10.1111/bcp.13403CrossRefPubMedPubMedCentral

10.

Smit EF, Garon EB, Reck M, Cappuzzo F, Bidoli P, Cohen RB, Gao L, O’Brien LM, Lee P, Zimmermann A, Ferry DR, Melemed AS, Perol M (2018) Exposure-response relationship for ramucirumab from the randomized, double-blind, phase 3 REVEL trial (docetaxel versus docetaxel plus ramucirumab) in second-line treatment of metastatic non-small cell lung cancer. Cancer Chemother Pharmacol 82(1):77–86. https://doi.org/10.1007/s00280-018-3560-5CrossRefPubMed

11.

Rosello S, Blasco I, Garcia Fabregat L, Cervantes A, Jordan K, clinicalguidelines@esmo.org EGCEa (2017) Management of infusion reactions to systemic anticancer therapy: ESMO Clinical Practice Guidelines. Ann Oncol 28(Suppl 4):100–118. https://doi.org/10.1093/annonc/mdx216CrossRef

12.

Bajaj G, Wang X, Agrawal S, Gupta M, Roy A, Feng Y (2017) Model-based population pharmacokinetic analysis of Nivolumab in patients with solid tumors. CPT Pharmacomet Syst Pharmacol 6(1):58–66. https://doi.org/10.1002/psp4.12143CrossRef

13.

Liu C, Yu J, Li H, Liu J, Xu Y, Song P, Liu Q, Zhao H, Xu J, Maher VE, Booth BP, Kim G, Rahman A, Wang Y (2017) Association of time-varying clearance of nivolumab with disease dynamics and its implications on exposure response analysis. Clin Pharmacol Ther 101(5):657–666. https://doi.org/10.1002/cpt.656CrossRefPubMed

14.

Baverel PG, Dubois VFS, Jin CY, Zheng Y, Song X, Jin X, Mukhopadhyay P, Gupta A, Dennis PA, Ben Y, Vicini P, Roskos L, Narwal R (2018) Population pharmacokinetics of durvalumab in cancer patients and association with longitudinal biomarkers of disease status. Clin Pharmacol Ther 103(4):631–642. https://doi.org/10.1002/cpt.982CrossRefPubMedPubMedCentral

15.

Beal SSL, Boeckmann A, Bauer RJ (2009) NONMEM user’s guides (1989–2009). Icon Development Solution, Ellicott City

16.

Lammerts van Bueren JJ, Rispens T, Verploegen S, van der Palen-Merkus T, Stapel S, Workman LJ, James H, van Berkel PH, van de Winkel JG, Platts-Mills TA, Parren PW (2011) Anti-galactose-alpha-1,3-galactose IgE from allergic patients does not bind alpha-galactosylated glycans on intact therapeutic antibody Fc domains. Nat Biotechnol 29(7):574–576. https://doi.org/10.1038/nbt.1912CrossRefPubMed

17.

Chung CH, Mirakhur B, Chan E, Le QT, Berlin J, Morse M, Murphy BA, Satinover SM, Hosen J, Mauro D, Slebos RJ, Zhou Q, Gold D, Hatley T, Hicklin DJ, Platts-Mills TA (2008) Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med 358(11):1109–1117. https://doi.org/10.1056/NEJMoa074943CrossRefPubMedPubMedCentral

18.

Hashimoto N, Mitani S, Taniguchi H, Narita Y, Kato K, Masuishi T, Kadowaki S, Onishi S, Tajika M, Takahashi S, Shimomura K, Takahata C, Hotta E, Kobara M, Muro K (2019) A prospective trial evaluating the safety of a shortened infusion of ramucirumab in patients with gastrointestinal cancer. Oncologist 24(2):159-e166. https://doi.org/10.1634/theoncologist.2018-0580CrossRefPubMed

19.

Bauer S, Fadeyi M, Chan S (2019) A study of tolerability, satisfaction, and cost reduction using a 10% immunoglobulin product at higher administration rates. J Infus Nurs 42(6):297–302. https://doi.org/10.1097/NAN.0000000000000347CrossRefPubMed

20.

Daniel SR, McDermott JD Jr, Le C, Pierce CA, Ziskind MA, Ellis LA (2018) A real-world, multi-site, observational study of infusion time and treatment satisfaction with rheumatoid arthritis patients treated with intravenous golimumab or infliximab. J Med Econ 21(7):724–731. https://doi.org/10.1080/13696998.2018.1472098CrossRefPubMed

21.

Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, Dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J, Investigators RT (2014) Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 383(9911):31–39. https://doi.org/10.1016/S0140-6736(13)61719-5CrossRefPubMed

22.

Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A, Group RS (2014) 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 15(11):1224–1235. https://doi.org/10.1016/S1470-2045(14)70420-6CrossRefPubMed

23.

Reck M, Paz-Ares L, Bidoli P, Cappuzzo F, Dakhil S, Moro-Sibilot D, Borghaei H, Johnson M, Jotte R, Pennell NA, Shepherd FA, Tsao A, Thomas M, Carter GC, Chan-Diehl F, Alexandris E, Lee P, Zimmermann A, Sashegyi A, Perol M (2017) Outcomes in patients with aggressive or refractory disease from REVEL: a randomized phase III study of docetaxel with ramucirumab or placebo for second-line treatment of stage IV non-small-cell lung cancer. Lung Cancer 112:181–187. https://doi.org/10.1016/j.lungcan.2017.07.038CrossRefPubMed

24.

Tabernero J, Yoshino T, Cohn AL, Obermannova R, Bodoky G, Garcia-Carbonero R, Ciuleanu TE, Portnoy DC, Van Cutsem E, Grothey A, Prausova J, Garcia-Alfonso P, Yamazaki K, Clingan PR, Lonardi S, Kim TW, Simms L, Chang SC, Nasroulah F, Investigators RS (2015) 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 16(5):499–508. https://doi.org/10.1016/S1470-2045(15)70127-0CrossRefPubMed

25.

Zhu AX, Park JO, Ryoo BY, Yen CJ, Poon R, Pastorelli D, Blanc JF, Chung HC, Baron AD, Pfiffer TE, Okusaka T, Kubackova K, Trojan J, Sastre J, Chau I, Chang SC, Abada PB, Yang L, Schwartz JD, Kudo M, Investigators RT (2015) Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol 16(7):859–870. https://doi.org/10.1016/S1470-2045(15)00050-9CrossRef

26.

Zhu AX, Kang YK, Yen CJ, Finn RS, Galle PR, Llovet JM, Assenat E, Brandi G, Pracht M, Lim HY, Rau KM, Motomura K, Ohno I, Merle P, Daniele B, Shin DB, Gerken G, Borg C, Hiriart JB, Okusaka T, Morimoto M, Hsu Y, Abada PB, Kudo M, Investigators R-s (2019) Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 20(2):282–296. https://doi.org/10.1016/S1470-2045(18)30937-9CrossRef

27.

Fuchs CS, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran SE, Van Cutsem E, Ilson DH, Alsina M, Chau I, Lacy J, Ducreux M, Mendez GA, Alavez AM, Takahari D, Mansoor W, Enzinger PC, Gorbounova V, Wainberg ZA, Hegewisch-Becker S, Ferry D, Lin J, Carlesi R, Das M, Shah MA, Group RS (2019) Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 20(3):420–435. https://doi.org/10.1016/S1470-2045(18)30791-5CrossRefPubMed

28.

Petrylak DP, de Wit R, Chi KN, Drakaki A, Sternberg CN, Nishiyama H, Castellano D, Hussain S, Flechon A, Bamias A, Yu EY, van der Heijden MS, Matsubara N, Alekseev B, Necchi A, Geczi L, Ou YC, Coskun HS, Su WP, Hegemann M, Percent IJ, Lee JL, Tucci M, Semenov A, Laestadius F, Peer A, Tortora G, Safina S, Del Muro XG, Rodriguez-Vida A, Cicin I, Harputluoglu H, Widau RC, Liepa AM, Walgren RA, Hamid O, Zimmermann AH, Bell-McGuinn KM, Powles T, Investigators Rs (2017) Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial. Lancet 390(10109):2266–2277. https://doi.org/10.1016/S0140-6736(17)32365-6CrossRef

Title: Evaluating clinical impact of a shortened infusion duration for ramucirumab: a model-based approach
Authors: Ling Gao
Yiu-Keung Lau
Ran Wei
Lisa O’Brien
Amanda Long
Yongzhe Piao
Paolo Abada
Publication date: 01-05-2021
Publisher: Springer Berlin Heidelberg
Keyword: Ramucirumab
Published in: Cancer Chemotherapy and Pharmacology / Issue 5/2021
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04223-9

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