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Clinical Trial
. 2021 May;24(3):721-730.
doi: 10.1007/s10120-020-01153-6. Epub 2021 Mar 23.

Patient-reported outcomes from the phase II FAST trial of zolbetuximab plus EOX compared to EOX alone as first-line treatment of patients with metastatic CLDN18.2+ gastroesophageal adenocarcinoma

Florian Lordick  1 , Salah-Eddin Al-Batran  2 , Arijit Ganguli  3 , Robert Morlock  4 , Ugur Sahin  5   6   7 , Özlem Türeci  7   8
Affiliations
Clinical Trial

Patient-reported outcomes from the phase II FAST trial of zolbetuximab plus EOX compared to EOX alone as first-line treatment of patients with metastatic CLDN18.2+ gastroesophageal adenocarcinoma

Florian Lordick et al. Gastric Cancer. 2021 May.

Abstract

Background: Zolbetuximab plus first-line EOX (epirubicin, oxaliplatin, capecitabine; ZOL/EOX) significantly prolonged progression-free survival and overall survival in the FAST trial vs EOX alone. We report the patient-reported outcomes (PROs) of FAST in patients with advanced gastroesophageal adenocarcinoma.

Methods: Patients were randomized to ZOL/EOX or EOX alone. Patients could receive ≤ 8 EOX cycles and remained on zolbetuximab until disease progression. PROs were collected using the EORTC QLQ-C30 and QLQ-STO22 before drug administration at day 1/cycle 1, day 1/cycle 5, end of EOX treatment, and q12w thereafter until disease progression. Time to deterioration (TTD), defined as the first meaningful worsening from baseline, in the individual QLQ-C30/QLQ-STO22 scores was analyzed. Longitudinal changes in scores from baseline were analyzed using a mixed-effects model for repeated measures (MMRM).

Results: The per protocol population included 143 (ZOL/EOX: 69; EOX: 74) patients. Baseline QLQ-C30 and STO22 scores were comparable between arms and denoted intermediate-to-high quality of life (QoL), intermediate-to-low global health status (GHS) and low symptom burden. Descriptive analyses showed no differences between arms until end of EOX but maintenance therapy with zolbetuximab was associated with better QoL and less symptom burden thereafter. TTD for most scores favored ZOL/EOX over EOX and reached statistical significance for GHS (p = 0.008). MMRM results support TTD findings; no statistically significant differences were observed between arms in any score except for nausea and vomiting (p = 0.0181 favoring EOX).

Conclusions: ZOL/EOX allowed patients to maintain good QoL and low symptom burden for longer than EOX alone.

Keywords: Antibodies; Biomarkers; Monoclonal; Patient-reported outcomes; Quality of life; Stomach cancer.

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Conflict of interest statement

Florian Lordick reports personal fees and/or grants from Astellas, AstraZeneca, BMS, BioNTech, Lilly, Elsevier, Infomedica, Merck, MSD, Roche, Servier, and Amgen. Salah-Eddin Al-Batran reports advisory role from Merck, Roche, Celgene, Lilly, Nordic Pharma, Bristol-Myers Squibb, MSD Sharp & Dohme; speaker role from Roche, Celgene, Lilly, Nordic Pharma, AIO gGmbH, MCI, Promedicis, Forum für Medizinische Fortbildung; CEO/founder of IKF Klinische Krebsforschung GmbH; and clinical trial fees from Sanofi, Merck, Roche, Celgene, Vifor, Medac, Hospira, Lilly, German Cancer Aid (Krebshilfe), and German Research Foundation; and translational research from the Federal Ministry of Education and Research. Arijit Ganguli is an employee of Astellas Pharma, Inc. Robert Morlock is a former independent consultant with YouCareChoice supporting Astellas Pharma, Inc., and reports personal fees from Astellas Pharma, Inc., Abbot Medical Optics, Ironwood, and Genentech. Ugur Sahin reports co-founder and shareholder at Ganymed and also holds several patents, with royalties paid by Astellas; founder, chief executive officer, and shareholder of BioNTech. Özlem Türeci reports founder and chief executive officer of Ganymed until the end of 2016; currently an employee and chief medical officer of BioNTech; patents for the investigational agent, zolbetuximab, with royalties paid by Astellas; consultancy fees from Astellas Pharma.

Figures

Fig. 1
Fig. 1
Descriptive analysis of mean change from baseline over time for (a) global health status/quality of life, (b) physical functioning, and (c) nausea/vomiting (PPS). Mean change from baseline throughout the study is provided for (a) global health status, (b) physical functioning, and (c) nausea/vomiting. Abbreviations: EOT: end of EOX treatment; EOX: epirubicin, oxaliplatin, and capecitabine; P-cycle: post end of EOX treatment cycle; PPS: per protocol set; ZOL/EOX: zolbetuximab 800/600 mg/m2 plus EOX
Fig. 2
Fig. 2
Kaplan–Meier curves of time to deterioration in HRQoL based on EORTC QLQ-C30 global health status/quality of life score (PPS). EORTC LQ-C30: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30; EOX: epirubicin, oxaliplatin, and capecitabine; HRQoL: health-related quality of life; PPS: per protocol set; ZOL/EOX: zolbetuximab 800/600 mg/m2 plus EOX
Fig. 3
Fig. 3
Change from baseline in (a) global health status/quality of life, (b) EORTC QLQ-STO22 total score, and (c) nausea/vomiting (MMRM analysis; PPS). Data are provided as LS mean and standard error change from baseline for (a) the EORTC QLQ-C30 global health status, (b) the EORTC QLQ-STO22 total score, and (c) nausea/vomiting. Abbreviations: EORTC LQ-C30: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30; EORTC QLQ-STO22: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-gastric cancer module; EOT: end of EOX treatment; EOX: epirubicin, oxaliplatin, and capecitabine; Interval 2: time of cycle 5 of EOX with a window of 15 days; Interval 4: planned time of the end of EOX treatment with a window of 15 days); interval 5: from the end of EOX treatment until the last PRO collection; MMRM: mixed model for repeated measures; PPS: per protocol set; ZOL/EOX: zolbetuximab 800/600 mg/m2 plus EOX
Fig. 4
Fig. 4
Change from baseline at cycle 8 in the overall HRQoL in the (a) overall FAST population (PPS) and (b) the ≥ 70% CLDN18.2 expressing patients. CLDN18.2: Claudin 18 splice variant 2; EOX: epirubicin, oxaliplatin, and capecitabine; HRQoL: health-related quality of life; PPS: per protocol set; ZOL/EOX: zolbetuximab 800/600 mg/m2 plus EOX
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