Please use this identifier to cite or link to this item: http://dx.doi.org/10.25673/115489
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dc.contributor.authorThuss-Patience, Peter-
dc.contributor.authorSchultheiß, Christoph-
dc.contributor.authorPaschold, Lisa-
dc.contributor.authorBinder, Mascha-
dc.contributor.author[und viele weitere]-
dc.date.accessioned2024-03-25T08:22:01Z-
dc.date.available2024-03-25T08:22:01Z-
dc.date.issued2024-
dc.identifier.urihttps://opendata.uni-halle.de//handle/1981185920/117443-
dc.identifier.urihttp://dx.doi.org/10.25673/115489-
dc.description.abstractImportance: Adding immune checkpoint inhibitors to chemotherapy has been associated with improved outcomes in metastatic esophagogastric adenocarcinoma, but treatment combinations and optimal patient selection need to be established. Objective: To investigate the efficacy and tolerability of the programmed cell death ligand 1 (PDL-1) inhibitor avelumab with paclitaxel plus ramucirumab. Design, Setting, and Participants: This multicenter, single-group, phase 2 nonrandomized controlled trial was conducted among patients with second-line metastatic esophagogastric adenocarcinoma. Patients pretreated with platinum plus fluoropyrimidine between April 2019 and November 2020 across 10 German centers (median follow-up, 27.4 months [95% CI 22.0-32.9 months]) were included. Data analysis was performed from January to December 2022. Interventions: Patients received ramucirumab at 8 mg/kg on days 1 and 15, avelumab at 10 mg/kg on days 1 and 15, and paclitaxel at 80 mg/m2 on days 1, 8, and 15 every 4 weeks. Main Outcomes and Measures: The prespecified primary end point was overall survival (OS) rate at 6 months, with the experimental therapy considered insufficiently active with an OS rate of 50% or less and a promising candidate with an OS rate of 65% or greater. Results: Of 60 enrolled patients, 59 patients (median [range] age, 64 [18-81] years; 47 males [70.7%]) were evaluable, including 30 patients with metastatic adenocarcinoma of the stomach and 29 patients with gastroesophageal junction. All patients were pretreated with platinum plus fluoropyrimidine, and 40 patients (67.8%) had received prior taxanes; 24 of 56 evaluable patients (42.9%) had a PDL-1 combined positive score (CPS) of 5 or greater, centrally assessed. The OS rate at 6 months was 71.2% (95% CI, 61.5%-83.7%). The median OS in the intention-to-treat population (59 patients) was 10.6 months (95% CI, 8.4-12.8 months) overall. Among patients assessable by central pathology, median OS was 9.4 months (95% CI, 7.2-11.7 months) in 32 patients with a PDL-1 CPS less than 5 and 14.0 months (95% CI, 6.0-22.1 months) in 24 patients with a PDL-1 CPS of 5 or greater (P = .25). Treatment was generally well tolerated, without unexpected toxicities. Patients with higher vs lower than median T cell repertoire richness showed an increased median OS of 20.4 months (95% CI, 7.7-33.0 months) compared with 8.3 months (95% CI, 3.7-12.9 months; hazard ratio, 0.43; 95% CI, 0.23-0.81; P = .008). Patients with lower vs higher than median cell-free DNA burden had a median OS of 19.2 months (95% CI, 8.9-29.6 months) compared with 7.3 months (95% CI, 3.2-11.4 months; hazard ratio, 0.30; 95% CI, 0.16-0.59; P < .001). Conclusions and relevance: In this study, the combination of avelumab with paclitaxel plus ramucirumab showed favorable efficacy and tolerability in the second-line treatment for metastatic esophagogastric adenocarcinoma. A PDL-1 CPS score of 5 or greater, cell-free DNA level less than the median, and T cell repertoire richness greater than the median were associated with increased median OS.eng
dc.language.isoeng-
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.subject.ddc610-
dc.titleRamucirumab, Avelumab, and Paclitaxel as second-line treatment in esophagogastric adenocarcinoma : the phase 2 RAP (AIO-STO-0218) nonrandomized controlled trialeng
dc.typeArticle-
local.versionTypepublishedVersion-
local.bibliographicCitation.journaltitleJAMA network open-
local.bibliographicCitation.volume7-
local.bibliographicCitation.issue1-
local.bibliographicCitation.pagestart1-
local.bibliographicCitation.pageend13-
local.bibliographicCitation.publishernameAmerican Medical Association-
local.bibliographicCitation.publisherplaceChicago, Ill.-
local.bibliographicCitation.doi10.1001/jamanetworkopen.2023.52830-
local.openaccesstrue-
dc.identifier.ppn1884181902-
cbs.publication.displayform2024-
local.bibliographicCitation.year2024-
cbs.sru.importDate2024-03-25T08:20:57Z-
local.bibliographicCitationEnthalten in JAMA network open - Chicago, Ill. : American Medical Association, 2018-
local.accessrights.dnbfree-
Appears in Collections:Open Access Publikationen der MLU

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