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Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER).
Ann Oncol 2020; 31(2):228-235AO

Abstract

BACKGROUND

Palliative chemotherapy of advanced oesophageal squamous cell cancer (ESCC) consists of cisplatin/5-fluorouracil (CF) to target epidermal growth factor receptor (EGFR) with panitumumab (P); chemotherapy enhanced overall survival (OS) in advanced colorectal or squamous cell head and neck cancers. With prospective serum and tumour biomarkers, we tested if P added to CF (CFP) improved OS in advanced ESCC.

PATIENTS AND METHODS

Eligible patients with confirmed ESCC that was not curatively resectable or did not qualify for definitive radiochemotherapy, were randomised 1 : 1 to receive CF [cisplatin (C) 100 mg/m2 i.v., day 1; 5-fluorouracil (F) 1000 mg/m2 i.v., days 1-4] or CF plus P (9 mg/kg, i.v., day 1, each q3-week cycle) until progressive disease or unacceptable toxicity. Safety was reviewed by the Data Safety Monitoring Board after 40, 70 and 100 patients who completed at least one cycle. After 53 enrolled patients, cisplatin was reduced from 100 mg/m2 to 80 mg/m2.

RESULTS

The trial was stopped early based on interim efficacy results triggered by the third safety analysis: median OS (mOS) favoured CF over CFP, regardless of cisplatin dose [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.06-2.98; P = 0.028]. In the final analysis, mOS was 10.2 versus 9.4 months for CF versus CFP, respectively (HR 1.17, 95% CI 0.79-1.75; P = 0.43). One hundred (70.4%) of 142 patients in the safety population died, 51 (51.0%) with CFP. Most deaths were related to disease progression [44/49 (90%) deaths in CF versus 34/51 (67%) deaths in CFP]; objective responses [27/73 (37.0%)] were identical. The most common serious adverse events were kidney injury [3 (4.3%) versus 7 (9.7%)], general health deterioration [5 (7.1%) versus 5 (6.9%)] and dysphagia [4 (5.7%) versus 4 (5.6%)] in CF versus CFP, respectively. There were three (4.3%) and 17 (23.6%) common terminology criteria for adverse events (CTCAE) grade 5 events in CF versus CFP, respectively. Low soluble (s)EGFR levels were associated with better progression-free survival; sEGFR was induced under CFP.

CONCLUSION

EGFR inhibition added to CF did not improve survival in unselected advanced ESCC patients. The results support further liquid biopsy studies.

TRIAL REGISTRATION

ClinicalTrials.gov (NCT01627379) and EudraCT (2010-020606-15).

Authors+Show Affiliations

1st Department of Internal Medicine, Johannes Gutenberg-University Mainz, Mainz, Germany. Electronic address: markus.moehler@unimedizin-mainz.de.1st Department of Internal Medicine, Johannes Gutenberg-University Mainz, Mainz, Germany.Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charité - University Medicine Berlin, Berlin, Germany.Institute of Oncology, Davidoff Center, Rabin Medical Center, Petach Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.Department of Internal Medicine, University Hospital Essen, Essen, Germany.Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany.Medical Department III, University Hospital Mannheim, Mannheim, Germany.Institute of Clinical Cancer Research, Hospital North-West, Frankfurt, Germany.Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.Oncology Leer-Emden-Papenburg, Leer, Germany.Gastroenterology, Caritas Hospital, Saarbrücken, Germany.1st Medical Department and University Cancer Center Leipzig, University of Leipzig Medical Center, Leipzig, Germany.Department of Medical Oncology, Hospital Universitari Vall d'Hebron and Vall d'Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain.Medical Department III, University Hospital Rostock, Rostock, Germany.3rd Medical Department, Cancer Research Institute, Paracelsus Medical University Salzburg, Salzburg, Austria.Department of Internal Medicine V, Medical University Innsbruck, Innsbruck, Austria.Institute of Pathology, Johannes Gutenberg-University Mainz, Mainz, Germany.Institute of Pathology, School of Medicine, Technical University of Munich, Munich, Germany.University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium.Medical Department III, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31959339

Citation

Moehler, M, et al. "Cisplatin and 5-fluorouracil With or Without Epidermal Growth Factor Receptor Inhibition Panitumumab for Patients With Non-resectable, Advanced or Metastatic Oesophageal Squamous Cell Cancer: a Prospective, Open-label, Randomised Phase III AIO/EORTC Trial (POWER)." Annals of Oncology : Official Journal of the European Society for Medical Oncology, vol. 31, no. 2, 2020, pp. 228-235.
Moehler M, Maderer A, Thuss-Patience PC, et al. Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER). Ann Oncol. 2020;31(2):228-235.
Moehler, M., Maderer, A., Thuss-Patience, P. C., Brenner, B., Meiler, J., Ettrich, T. J., ... Lorenzen, S. (2020). Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER). Annals of Oncology : Official Journal of the European Society for Medical Oncology, 31(2), pp. 228-235. doi:10.1016/j.annonc.2019.10.018.
Moehler M, et al. Cisplatin and 5-fluorouracil With or Without Epidermal Growth Factor Receptor Inhibition Panitumumab for Patients With Non-resectable, Advanced or Metastatic Oesophageal Squamous Cell Cancer: a Prospective, Open-label, Randomised Phase III AIO/EORTC Trial (POWER). Ann Oncol. 2020;31(2):228-235. PubMed PMID: 31959339.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER). AU - Moehler,M, AU - Maderer,A, AU - Thuss-Patience,P C, AU - Brenner,B, AU - Meiler,J, AU - Ettrich,T J, AU - Hofheinz,R-D, AU - Al-Batran,S E, AU - Vogel,A, AU - Mueller,L, AU - Lutz,M P, AU - Lordick,F, AU - Alsina,M, AU - Borchert,K, AU - Greil,R, AU - Eisterer,W, AU - Schad,A, AU - Slotta-Huspenina,J, AU - Van Cutsem,E, AU - Lorenzen,S, Y1 - 2019/12/16/ PY - 2019/06/17/received PY - 2019/10/10/revised PY - 2019/10/15/accepted PY - 2020/1/22/entrez KW - 5-fluorouracil KW - EGFR KW - cisplatin KW - oesophageal squamous cell cancer KW - palliative chemotherapy KW - panitumumab SP - 228 EP - 235 JF - Annals of oncology : official journal of the European Society for Medical Oncology JO - Ann. Oncol. VL - 31 IS - 2 N2 - BACKGROUND: Palliative chemotherapy of advanced oesophageal squamous cell cancer (ESCC) consists of cisplatin/5-fluorouracil (CF) to target epidermal growth factor receptor (EGFR) with panitumumab (P); chemotherapy enhanced overall survival (OS) in advanced colorectal or squamous cell head and neck cancers. With prospective serum and tumour biomarkers, we tested if P added to CF (CFP) improved OS in advanced ESCC. PATIENTS AND METHODS: Eligible patients with confirmed ESCC that was not curatively resectable or did not qualify for definitive radiochemotherapy, were randomised 1 : 1 to receive CF [cisplatin (C) 100 mg/m2 i.v., day 1; 5-fluorouracil (F) 1000 mg/m2 i.v., days 1-4] or CF plus P (9 mg/kg, i.v., day 1, each q3-week cycle) until progressive disease or unacceptable toxicity. Safety was reviewed by the Data Safety Monitoring Board after 40, 70 and 100 patients who completed at least one cycle. After 53 enrolled patients, cisplatin was reduced from 100 mg/m2 to 80 mg/m2. RESULTS: The trial was stopped early based on interim efficacy results triggered by the third safety analysis: median OS (mOS) favoured CF over CFP, regardless of cisplatin dose [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.06-2.98; P = 0.028]. In the final analysis, mOS was 10.2 versus 9.4 months for CF versus CFP, respectively (HR 1.17, 95% CI 0.79-1.75; P = 0.43). One hundred (70.4%) of 142 patients in the safety population died, 51 (51.0%) with CFP. Most deaths were related to disease progression [44/49 (90%) deaths in CF versus 34/51 (67%) deaths in CFP]; objective responses [27/73 (37.0%)] were identical. The most common serious adverse events were kidney injury [3 (4.3%) versus 7 (9.7%)], general health deterioration [5 (7.1%) versus 5 (6.9%)] and dysphagia [4 (5.7%) versus 4 (5.6%)] in CF versus CFP, respectively. There were three (4.3%) and 17 (23.6%) common terminology criteria for adverse events (CTCAE) grade 5 events in CF versus CFP, respectively. Low soluble (s)EGFR levels were associated with better progression-free survival; sEGFR was induced under CFP. CONCLUSION: EGFR inhibition added to CF did not improve survival in unselected advanced ESCC patients. The results support further liquid biopsy studies. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01627379) and EudraCT (2010-020606-15). SN - 1569-8041 UR - https://www.unboundmedicine.com/medline/citation/31959339/Cisplatin_and_5-fluorouracil_with_or_without_epidermal_growth_factor_receptor_inhibition_panitumumab_for_patients_with_non-resectable,_advanced_or_metastatic_oesophageal_squamous_cell_cancer:_a_prospective,_open-label,_randomised_phase_III_AIO/EORTC_trial_(POWER) L2 - https://linkinghub.elsevier.com/retrieve/pii/S0923-7534(19)36074-0 DB - PRIME DP - Unbound Medicine ER -