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

Shah, M.A. and Udrea, A.A. and Bondarenko, I. and Mansoor, W. and Sánchez, R.G. and Sarosiek, T. and Bozzarelli, S. and Schenker, M. and Gomez-Martin, C. and Morgan, C. and Özgüroglu, M. and Pikiel, J. and Kalofonos, H.P. and Wojcik, E. and Buchler, T. and Swinson, D. and Cicin, I. and Joseph, M. and Vynnychenko, I. and Luft, A.V. and Enzinger, P.C. and Salek, T. and Papandreou, C. and Tournigand, C. and Maiello, E. and Wei, R. and Ferry, D. and Gao, L. and Oliveira, J.M. and Ajani, J.A. (2022) 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. Cancers, Vol.14 (iss. 5). p. 1168. ISSN 2072-6694

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Abstract

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.

Item Type:	Article
Additional Information:	Shah MA, Udrea AA, Bondarenko I, Mansoor W, Sánchez RG, Sarosiek T, Bozzarelli S, Schenker M, Gomez-Martin C, Morgan C, Özgüroğlu M, Pikiel J, Kalofonos HP, Wojcik E, Buchler T, Swinson D, Cicin I, Joseph M, Vynnychenko I, Luft AV, Enzinger PC, Salek T, Papandreou C, Tournigand C, Maiello E, Wei R, Ferry D, Gao L, Oliveira JM, Ajani JA. 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. Cancers. 2022; 14(5):1168. https://doi.org/10.3390/cancers14051168
Uncontrolled Keywords:	angiogenesis; gastric adenocarcinoma; ramucirumab; vascular endothelial growth factor receptor
Subjects:	Oncology
Divisions:	Departments > Department of Oncology and Medical Radiology
Depositing User:	Елена Шрамко
Date Deposited:	16 Mar 2022 09:17
Last Modified:	16 Mar 2022 09:17
URI:	http://repo.dma.dp.ua/id/eprint/7387

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