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: Shah MA; Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, NY 10021, USA., Udrea AA; Cancer Center, Medisprof SRL, 400641 Cluj-Napoca, Romania., Bondarenko I; Department of Oncology, Dnipropetrovsk Medical Academy, 49044 Dnipropetrovsk, Ukraine., Mansoor W; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK., Sánchez RG; Department of Medical Oncology, Catalan Institute of Oncology (ICO) Girona Hospital Dr Josep Trueta, 17007 Girona, Spain., Sarosiek T; Department of Clinical Oncology and Oncological Surgery, LUXMED Onkologia, 04125 Warszawa, Poland., Bozzarelli S; Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Milan, Italy., Schenker M; Centrul de Oncologie Sf. Nectarie SRL, 200542 Craiova, Romania.; Department of Medical Oncology, University of Medicine and Pharmacy Craiova, 200342 Craiova, Romania., Gomez-Martin C; Medical Oncology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain., Morgan C; Department of Clinical Oncology, Velindre Cancer Centre, Cardiff CF14 2TL, UK., Özgüroğlu M; Medical Oncology, Istanbul University, Cerrahpaşa, Fatih, Istanbul 34098, Turkey., Pikiel J; Department of Oncology, Copernicus Podmiot Leczniczy, 80-803 Gdańsk, Poland., Kalofonos HP; Department of Oncology, University General Hospital of Patras Rion, 26504 Patras, Greece., Wojcik E; NZOZ Centrum Medyczne HCP, 62-030 Luboń, Poland., Buchler T; Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, 14059 Prague, Czech Republic., Swinson D; Institute of Oncology, St James's University Hospital, Leeds LS9 7TF, UK., Cicin I; Medical Oncology, Trakya University, Edirne 22030, Turkey., Joseph M; Deanesly Centre, New Cross Hospital, Wolverhamptom WV10 0QP, UK., Vynnychenko I; Sumy Regional Oncology Center, Sumy State University, 40000 Sumy, Ukraine., Luft AV; Department of Oncology No 1 (Thoracic Surgery), Leningrad Regional Clinical Hospital, 194291 St. Petersburg, Russia., Enzinger PC; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Salek T; Department of Clinical Oncology, Narodny Onkologicky Ustav, 83310 Bratislava, Slovakia., Papandreou C; Department of Medical Oncology, Faculty of Medicine, University of Thessaly, Biopolis, 41223 Larissa, Greece., Tournigand C; Department of Medical Oncology, Henri Mondor et Albert Chenevier Teaching Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris-Est Creteil, 94000 Créteil, France., Maiello E; Oncology Unit, Foundation Casa Sollievo della Sofferenza IRCCS, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy., Wei R; Eli Lilly and Company, Indianapolis, IN 46225, USA., Ferry D; Eli Lilly and Company, New York, NY 10016, USA., Gao L; Eli Lilly and Company, New York, NY 10016, USA., Oliveira JM; Eli Lilly and Company, New York, NY 10016, USA., Ajani JA; Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Feb 24; Vol. 14 (5). Date of Electronic Publication: 2022 Feb 24.
DOI: 10.3390/cancers14051168
Abstrakt: 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.
Databáze: MEDLINE
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