Ramucirumab, Avelumab, and Paclitaxel as Second-Line Treatment in Esophagogastric Adenocarcinoma: The Phase 2 RAP (AIO-STO-0218) Nonrandomized Controlled Trial
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Ramucirumab, Avelumab, and Paclitaxel as Second-Line Treatment in Esophagogastric Adenocarcinoma: The Phase 2 RAP (AIO-STO-0218) Nonrandomized Controlled Trial : The Phase 2 RAP (AIO-STO-0218) Nonrandomized Controlled Trial. / Thuss-Patience, Peter; Högner, Anica; Goekkurt, Eray; Stahl, Michael; Kretzschmar, Albrecht; Götze, Thorsten; Stocker, Gertraud; Reichardt, Peter; Kullmann, Frank; Pink, Daniel; Bartels, Prisca; Jarosch, Armin; Hinke, Axel; Schultheiß, Christoph; Paschold, Lisa; Stein, Alexander; Binder, Mascha.
in: JAMA NETW OPEN, Jahrgang 7, Nr. 1, 02.01.2024, S. e2352830.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Ramucirumab, Avelumab, and Paclitaxel as Second-Line Treatment in Esophagogastric Adenocarcinoma: The Phase 2 RAP (AIO-STO-0218) Nonrandomized Controlled Trial
T2 - The Phase 2 RAP (AIO-STO-0218) Nonrandomized Controlled Trial
AU - Thuss-Patience, Peter
AU - Högner, Anica
AU - Goekkurt, Eray
AU - Stahl, Michael
AU - Kretzschmar, Albrecht
AU - Götze, Thorsten
AU - Stocker, Gertraud
AU - Reichardt, Peter
AU - Kullmann, Frank
AU - Pink, Daniel
AU - Bartels, Prisca
AU - Jarosch, Armin
AU - Hinke, Axel
AU - Schultheiß, Christoph
AU - Paschold, Lisa
AU - Stein, Alexander
AU - Binder, Mascha
PY - 2024/1/2
Y1 - 2024/1/2
N2 - IMPORTANCE: 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.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03966118.
AB - IMPORTANCE: 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.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03966118.
KW - Humans
KW - Male
KW - Middle Aged
KW - Adenocarcinoma/drug therapy
KW - Antibodies, Monoclonal, Humanized
KW - Cell-Free Nucleic Acids
KW - Paclitaxel/therapeutic use
KW - Platinum
KW - Ramucirumab
KW - Female
KW - Adolescent
KW - Young Adult
KW - Adult
KW - Aged
KW - Aged, 80 and over
U2 - 10.1001/jamanetworkopen.2023.52830
DO - 10.1001/jamanetworkopen.2023.52830
M3 - SCORING: Journal article
C2 - 38261316
VL - 7
SP - e2352830
JO - JAMA NETW OPEN
JF - JAMA NETW OPEN
SN - 2574-3805
IS - 1
ER -