AGAPP: efficacy of first-line cisplatin, 5-fluorouracil with afatinib in inoperable gastric and gastroesophageal junction carcinomas. A Hellenic Cooperative Oncology Group study

Authors

  • George Zarkavelis Department of Medical Oncology, University of Ioannina, Ioannina, Greece;  Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece
  • Epaminontas Samantas Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece
  • Georgia-Angeliki Koliou Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece
  • Kyriaki Papadopoulou Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki, Thessaloniki, Greece
  • Davide Mauri Department of Medical Oncology, University of Ioannina, Ioannina, Greece;  Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece
  • Gerasimos Aravantinos Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece
  • Anna Batistatou Department of Pathology, Ioannina University Hospital, Ioannina, Greece
  • Elissavet Pazarli Department of Pathology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece
  • Dimitrios Tryfonopoulos Second Department of Internal Medicine, Agios Savvas Cancer Hospital, Athens, Greece
  • Anna Tsipoura Department of Pathology, Agii Anargiri Cancer Hospital, Athens, Greece
  • Mattheos Bobos Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki, Thessaloniki, Greece
  • Amanda Psyrri Section of Medical Oncology, Department of Internal Medicine, Attikon University Hospital, Faculty of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
  • Thomas Makatsoris Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece
  • Constantina Petraki Department of Pathology, Metropolitan Hospital, Piraeus, Greece
  • Dimitrios Pectasides Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece
  • George Fountzilas Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki, Thessaloniki, Greece;  Aristotle University of Thessaloniki, Thessaloniki, Greece;p German Oncology Center, Limassol, Cyprus
  • George Pentheroudakis Department of Medical Oncology, University of Ioannina, Ioannina, Greece;  Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece

DOI:

https://doi.org/10.1080/0284186X.2021.1912822

Keywords:

Gastric cancer, afatinib, chemotherapy, combination, anti-EGFR TKI

Abstract

Purpose

Gastric cancer is the fifth most common neoplasm worldwide with high rates of mortality. Afatinib, a low molecular, irreversible potent inhibitor of ErbB trans-membrane receptor family, has shown promising results according to preclinical and phase I clinical trial data when combined with chemotherapy. We aimed at evaluating the safety and efficacy of the combination of cisplatin, 5FU with afatinib in molecularly unselected patients with advanced gastric cancer.

Methods

Patients with locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma received first line combination therapy of cisplatin, 5FU and afatinib every 21 days, followed by afatinib maintenance monotherapy. The primary endpoint was the Objective Response Rate (ORR); secondary endpoints included Overall Survival (OS), Progression Free Survival (PFS) and the safety profile. Unplanned exploratory analysis of HER2 and tumor mutational profile was performed.

Results

Among 55 patients (ITT population) enrolled, 19 (34.5%) achieved an objective tumor response; stable disease was observed in 16 patients (29.1%) and progressive disease in 10 patients (18.2%). The ORR in the per protocol population (PP) was 42.9%. Within a median follow-up of 56 months, the median PFS and OS in the ITT population was 5.0 and 8.7 months, respectively. Seven of the 47 HER2 informative cases carried HER2 positive tumors while TP53, BRCA2 and SMAD4 were the most frequently mutated genes. The most common toxicities were neutrophil count and white blood cell decrease occurring in 56.4% of patients, followed by anemia (50.9%), hyperglycemia (40%), and diarrhea (38.2%).

Conclusions

The combination of cisplatin/5FU with afatinib did not surpass the benchmarks of efficacy of the contemporary therapeutic regimens that are being applied for the treatment of patients with advanced gastric cancer. However, the observed efficacy and the improved safety profile support that our administration schedule may be further investigated to overcome toxicity problems when integrating afatinib to cytotoxic chemotherapy.

Clinical trial registration

NCT01743365

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Additional Files

Published

2021-06-03

How to Cite

Zarkavelis, G., Samantas, E., Koliou, G.-A., Papadopoulou, K., Mauri, D., Aravantinos, G., … Pentheroudakis, G. (2021). AGAPP: efficacy of first-line cisplatin, 5-fluorouracil with afatinib in inoperable gastric and gastroesophageal junction carcinomas. A Hellenic Cooperative Oncology Group study. Acta Oncologica, 60(6), 785–793. https://doi.org/10.1080/0284186X.2021.1912822

Issue

Vol. 60 No. 6 (2021): Acta Oncologica

Section

Articles