Evaluating Alternative Ramucirumab Doses as a Single Agent or with Paclitaxel in Second-Line Treatment of Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma: Results from Two Randomized, Open-Label, Phase II Studies

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dc.authoridMUSTAFA, ÖZGÜROĞLU/0000-0002-8417-8628
dc.authoridBozzarelli, Silvia/0000-0002-8118-7342
dc.authoridSchenker, Michael/0000-0003-2645-6391
dc.authoridBondarenko, Igor N/0000-0002-7071-2471
dc.authoridBondarenko, Igor/0000-0002-7071-2471
dc.authoridShah, Manish/0000-0002-6913-9655
dc.authoridBuchler, Tomas/0000-0001-6667-994X
dc.authorwosidShah, Manish A/AHI-4322-2022
dc.authorwosidMUSTAFA, ÖZGÜROĞLU/A-8234-2016
dc.authorwosidBozzarelli, Silvia/ADF-0978-2022
dc.authorwosidOliveira, Joana/KHV-0466-2024
dc.authorwosidSchenker, Michael/AAD-6920-2022
dc.authorwosidBondarenko, Igor N/GQP-1497-2022
dc.authorwosidBondarenko, Igor/U-5156-2017
dc.contributor.authorShah, Manish A.
dc.contributor.authorUdrea, Anghel Adrian
dc.contributor.authorBondarenko, Igor
dc.contributor.authorMansoor, Was
dc.contributor.authorSanchez, Raquel Guardeno
dc.contributor.authorSarosiek, Tomasz
dc.contributor.authorBozzarelli, Silvia
dc.date.accessioned2024-06-12T10:51:42Z
dc.date.available2024-06-12T10:51:42Z
dc.date.issued2022
dc.departmentTrakya Üniversitesien_US
dc.description.abstractSimple Summary Ramucirumab is indicated at a dosage of 8 mg/kg every 2 weeks as monotherapy or in combination with paclitaxel for second-line advanced/metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma. A post hoc analysis of the phase III trials REGARD and RAINBOW suggested a positive correlation between ramucirumab exposure and efficacy. Studies JVDB and JVCZ explored different ramucirumab dosing regimens as monotherapy and in combination with paclitaxel, respectively. Here we report results from these studies, in which JVDB evaluated the pharmacokinetics and safety of the currently registered dosing regimen for ramucirumab monotherapy and three exploratory dosing regimens, and JVCZ evaluated the efficacy and safety of a higher dosing regimen of ramucirumab in combination with paclitaxel in second-line gastric/GEJ adenocarcinoma. Overall, the safety profiles were similar between the registered dose and the exploratory dosing regimens. However, a lack of a dose/exposure-response relationship supports the standard dose of ramucirumab as second-line treatment for patients with advanced/metastatic gastric/GEJ adenocarcinoma. Studies JVDB and JVCZ examined alternative ramucirumab dosing regimens as monotherapy or combined with paclitaxel, respectively, in patients with advanced/metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma. For JVDB, randomized patients (N = 164) received ramucirumab monotherapy at four doses: 8 mg/kg every 2 weeks (Q2W) (registered dose), 12 mg/kg Q2W, 6 mg/kg weekly (QW), or 8 mg/kg on days 1 and 8 (D1D8) every 3 weeks (Q3W). The primary objectives were the safety and pharmacokinetics of ramucirumab monotherapy. For JVCZ, randomized patients (N = 245) received paclitaxel (80 mg/m(2)-D1D8D15) plus ramucirumab (8 mg/kg- or 12 mg/kg-Q2W). The primary objective was progression-free survival (PFS) of 12 mg/kg-Q2W arm versus placebo from RAINBOW using meta-analysis. Relative to the registered dose, exploratory dosing regimens (EDRs) led to higher ramucirumab serum concentrations in both studies. EDR safety profiles were consistent with previous studies. In JVDB, serious adverse events occurred more frequently in the 8 mg/kg-D1D8-Q3W arm versus the registered dose; 6 mg/kg-QW EDR had a higher incidence of bleeding/hemorrhage. In JVCZ, PFS was improved with the 12 mg/kg plus paclitaxel combination versus placebo in RAINBOW; however, no significant PFS improvement was observed between the 12 mg/kg and 8 mg/kg arms. The lack of a dose/exposure-response relationship in these studies supports the standard dose of ramucirumab 8 mg/kg-Q2W as monotherapy or in combination with paclitaxel as second-line treatment for advanced/metastatic gastric/GEJ adenocarcinoma.en_US
dc.identifier.doi10.3390/cancers14051168
dc.identifier.issn2072-6694
dc.identifier.issue5en_US
dc.identifier.pmid35267477en_US
dc.identifier.scopus2-s2.0-85125171994en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.3390/cancers14051168
dc.identifier.urihttps://hdl.handle.net/20.500.14551/18460
dc.identifier.volume14en_US
dc.identifier.wosWOS:000768602200001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherMdpien_US
dc.relation.ispartofCancersen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAngiogenesisen_US
dc.subjectGastric Adenocarcinomaen_US
dc.subjectRamucirumaben_US
dc.subjectVascular Endothelial Growth Factor Receptoren_US
dc.subjectDouble-Blinden_US
dc.subjectMulticenteren_US
dc.subjectIpilimumaben_US
dc.subjectTrialsen_US
dc.subjectMetaanalysisen_US
dc.subjectMelanomaen_US
dc.subjectTherapyen_US
dc.titleEvaluating Alternative Ramucirumab Doses as a Single Agent or with Paclitaxel in Second-Line Treatment of Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma: Results from Two Randomized, Open-Label, Phase II Studiesen_US
dc.typeArticleen_US

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