TY - JOUR
T1 - Evaluating Alternative Ramucirumab Doses as a Single Agent or with Paclitaxel in Second-Line Treatment of Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma
T2 - Results from Two Randomized, Open-Label, Phase II Studies
AU - Shah, Manish A.
AU - Udrea, Anghel Adrian
AU - Bondarenko, Igor
AU - Mansoor, Was
AU - Sánchez, Raquel Guardeño
AU - Sarosiek, Tomasz
AU - Bozzarelli, Silvia
AU - Schenker, Michael
AU - Gomez-Martin, Carlos
AU - Morgan, Carys
AU - Özgüroğlu, Mustafa
AU - Pikiel, Joanna
AU - Kalofonos, Haralabos P.
AU - Wojcik, Elzbieta
AU - Buchler, Tomas
AU - Swinson, Daniel
AU - Cicin, Irfan
AU - Joseph, Mano
AU - Vynnychenko, Ihor
AU - Luft, Alexander Valerievich
AU - Enzinger, Peter C.
AU - Salek, Tomas
AU - Papandreou, Christos
AU - Tournigand, Christophe
AU - Maiello, Evaristo
AU - Wei, Ran
AU - Ferry, David
AU - Gao, Ling
AU - Oliveira, Joana M.
AU - Ajani, Jaffer A.
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Gastric adenocarcinoma
KW - Ramucirumab
KW - Vascular endothelial growth factor receptor
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U2 - 10.3390/cancers14051168
DO - 10.3390/cancers14051168
M3 - Article
C2 - 35267477
AN - SCOPUS:85125171994
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 5
M1 - 1168
ER -