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

Autor: Manish A. Shah, Anghel Adrian Udrea, Igor Bondarenko, Was Mansoor, Raquel Guardeño Sánchez, Tomasz Sarosiek, Silvia Bozzarelli, Michael Schenker, Carlos Gomez-Martin, Carys Morgan, Mustafa Özgüroğlu, Joanna Pikiel, Haralabos P. Kalofonos, Elzbieta Wojcik, Tomas Buchler, Daniel Swinson, Irfan Cicin, Mano Joseph, Ihor Vynnychenko, Alexander Valerievich Luft, Peter C. Enzinger, Tomas Salek, Christos Papandreou, Christophe Tournigand, Evaristo Maiello, Ran Wei, David Ferry, Ling Gao, Joana M. Oliveira, Jaffer A. Ajani
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cancers; Volume 14; Issue 5; Pages: 1168
ISSN: 2072-6694
DOI: 10.3390/cancers14051168
Popis: 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/m2-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.
Databáze: OpenAIRE
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