Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Basit Öğe Kaydı
dc.authoridSu, Harvey Yu-Li/0000-0002-1289-473X
dc.authoridFOMKIN, ROMAN N/0000-0001-6895-6445
dc.authoridMassari, Francesco/0000-0001-6476-6871
dc.authoridBamias, Aristotelis/0000-0002-5996-7262
dc.authoridAragon-Ching, Jeanny/0000-0002-6714-141X
dc.authoridBondarenko, Igor N/0000-0002-7071-2471
dc.authoridCicin, Irfan/0000-0002-7584-3868
dc.authorwosidSu, Harvey Yu-Li/N-9726-2019
dc.authorwosidFOMKIN, ROMAN N/C-6417-2016
dc.authorwosidCoşkun, Hasan Şenol/C-2070-2016
dc.authorwosidMassari, Francesco/K-7239-2016
dc.authorwosidBamias, Aristotelis/AAD-5332-2019
dc.authorwosidAragon-Ching, Jeanny/AAJ-4969-2020
dc.authorwosidNecchi, Andrea/L-6021-2017
dc.contributor.authorPetrylak, Daniel P.
dc.contributor.authorde Wit, Ronald
dc.contributor.authorChi, Kim N.
dc.contributor.authorDrakaki, Alexandra
dc.contributor.authorSternberg, Cora N.
dc.contributor.authorNishiyama, Hiroyuki
dc.contributor.authorCastellano, Daniel
dc.date.accessioned2024-08-04T20:43:59Z
dc.date.available2024-08-04T20:43:59Z
dc.date.issued2017
dc.departmentİnönü Üniversitesien_US
dc.description.abstractBackground Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population. Methods We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 sites in 23 countries. Previous treatment with one immune-checkpoint inhibitor was permitted. Patients were randomised (1:1) using an interactive web response system to receive intravenous docetaxel 75 mg/m(2) plus either intravenous ramucirumab 10 mg/kg or matching placebo on day 1 of repeating 21-day cycles, until disease progression or other discontinuation criteria were met. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat in the first 437 randomised patients. This study is registered with ClinicalTrials.gov, number NCT02426125. Findings Between July, 2015, and April, 2017, 530 patients were randomly allocated either ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267). Progression-free survival was prolonged significantly in patients allocated ramucirumab plus docetaxel versus placebo plus docetaxel (median 4.07 months [95% CI 2.96-4.47] vs 2.76 months [2.60-2.96]; hazard ratio [HR] 0.757, 95% CI 0.607-0.943; p=0.0118). A blinded independent central analysis was consistent with these results. An objective response was achieved by 53 (24.5%, 95% CI 18.8-30.3) of 216 patients allocated ramucirumab and 31 (14.0%, 9.4-18.6) of 221 assigned placebo. The most frequently reported treatment-emergent adverse events, regardless of causality, in either treatment group (any grade) were fatigue, alopecia, diarrhoea, decreased appetite, and nausea. These events occurred predominantly at grade 1-2 severity. The frequency of grade 3 or worse adverse events was similar for patients allocated ramucirumab and placebo (156 [60%] of 258 vs 163 [62%] of 265 had an adverse event), with no unexpected toxic effects. 63 (24%) of 258 patients allocated ramucirumab and 54 (20%) of 265 assigned placebo had a serious adverse event that was judged by the investigator to be related to treatment. 38 (15%) of 258 patients allocated ramucirumab and 43 (16%) of 265 assigned placebo died on treatment or within 30 days of discontinuation, of which eight (3%) and five (2%) deaths were deemed related to treatment by the investigator. Sepsis was the most common adverse event leading to death on treatment (four [2%] vs none [0%]). One fatal event of neutropenic sepsis was reported in a patient allocated ramucirumab. Interpretation To the best of our knowledge, ramucirumab plus docetaxel is the first regimen in a phase 3 study to show superior progression-free survival over chemotherapy in patients with platinum-refractory advanced urothelial carcinoma. These data validate inhibition of VEGFR-2 signalling as a potential new therapeutic treatment option for patients with urothelial carcinoma.en_US
dc.description.sponsorshipEli Lilly and Companyen_US
dc.description.sponsorshipEli Lilly and Company.en_US
dc.identifier.doi10.1016/S0140-6736(17)32365-6
dc.identifier.endpage2277en_US
dc.identifier.issn0140-6736
dc.identifier.issn1474-547X
dc.identifier.issue10109en_US
dc.identifier.pmid28916371en_US
dc.identifier.scopus2-s2.0-85029228806en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage2266en_US
dc.identifier.urihttps://doi.org/10.1016/S0140-6736(17)32365-6
dc.identifier.urihttps://hdl.handle.net/11616/97964
dc.identifier.volume390en_US
dc.identifier.wosWOS:000415645700025en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier Science Incen_US
dc.relation.ispartofLanceten_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectEndothelial Growth-Factoren_US
dc.subjectTransitional-Cell-Carcinomaen_US
dc.subjectBladder-Canceren_US
dc.subjectOpen-Labelen_US
dc.subject2nd-Line Therapyen_US
dc.subjectCombinationen_US
dc.subjectMethotrexateen_US
dc.subjectVinblastineen_US
dc.subjectDoxorubicinen_US
dc.subjectCisplatinen_US
dc.titleRamucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trialen_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayın Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu