S-1 maintenance therapy in Caucasian patients with metastatic esophagogastric adenocarcinoma–final results of the randomized AIO MATEO phase II trial

• Published in: ESMO open Vol. 8; no. 3; p. 101572
• Main Authors: Stocker, G., Lorenzen, S., Ettrich, T., Herz, A.-L., Longo, F., Kiani, A., Venerito, M., Trojan, J., Mahlberg, R., Moosmann, N., Chibaudel, B., Kubicka, S., Greil, R., Daum, S., Geissler, M., Larcher-Senn, J., Keller, G., Lordick, F., Haag, G.M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2023; Elsevier
• Subjects: Adenocarcinoma - pathology; Antineoplastic Combined Chemotherapy Protocols - adverse effects; chemotherapy; esophageal cancer; esophagogastric adenocarcinoma; gastric cancer; Humans; maintenance; Original Research; Progression-Free Survival; Quality of Life; S-1; esophageal cancer; gastric cancer; esophagogastric adenocarcinoma; maintenance; chemotherapy; S-1
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2023.101572

Platinum-fluoropyrimidine combinations are standard of care for treatment of metastatic esophagogastric adenocarcinoma. The optimal duration of first-line chemotherapy is unknown, however, and maintenance strategies have not yet been established. MATEO is an international randomized phase II trial exploring efficacy and safety of S-1 maintenance therapy in human epidermal growth factor receptor 2 (HER2)-negative advanced esophagogastric adenocarcinoma. After 3 months of first-line platinum-fluoropyrimidine-based induction therapy, patients without progression were randomized in a 2 : 1 allocation to receive S-1 monotherapy (arm A) or to continue combination chemotherapy (arm B). The primary objective was to show non-inferiority of overall survival in the S-1 maintenance group. Progression-free survival, adverse events, and quality of life were secondary endpoints. From 2014 to 2019, 110 and 55 patients were randomized in arm A and arm B, respectively (recruitment closed prematurely). Median overall survival from randomization was 13.4 months for arm A and 11.4 months for arm B [hazard ratio 0.97 (80% confidence interval 0.76-1.23), P = 0.86]. Median progression-free survival from randomization was 4.3 and 6.1 months for arm A versus arm B, respectively [hazard ratio 1.10 (80% confidence interval 0.86-1.39), P = 0.62]. Patients in arm A had numerically fewer treatment-related adverse events (84.9% versus 93.9%) and significantly less peripheral sensory polyneuropathy ≥grade 2 (9.4% versus 36.7%). S-1 maintenance following platinum-based induction therapy leads to non-inferior survival outcomes compared with the continuation of platinum-based combination. Toxicity patterns favor a fluoropyrimidine maintenance strategy. These data challenge the continued use of platinum combination chemotherapy after response to 3 months induction therapy in patients with advanced human epidermal growth factor receptor 2-negative esophagogastric adenocarcinoma. •S-1 maintenance therapy was applied following 3 months induction chemotherapy.•S-1 maintenance leads to non-inferior overall survival compared with continued poly-chemotherapy.•Toxicity pattern favors S-1 maintenance therapy.