Perioperative Cetuximab with Cisplatin and 5-Fluorouracil in Esogastric Adenocarcinoma: A Phase II Study
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Caroline Gronnier
1,*
,
Christophe Mariette
2,3,†,
Come Lepage
4,5,
Carole Monterymard
6,
Marine Jary
7,
Aurélie Ferru
8,
Mathieu Baconnier
9,
Xavier Adhoute
10,
David Tavan
11,
Hervé Perrier
12,
Véronique Guerin-Meyer
13,
Cédric Lecaille
14,
Nathalie Bonichon-Lamichhane
15,
Didier Pillon
16,
Oana Cojocarasu
17,
Joëlle Egreteau
18,
Xavier Benoit D’journo
19,
Laétitia Dahan
20,
Christophe Locher
21,
Patrick Texereau
22,
Denis Collet
1,
Pierre Michel
23,
Meher Ben Abdelghani
24,
Rosine Guimbaud
25,
Marie Muller
26,
Olivier Bouché
27,‡ and
Guillaume Piessen
2,3,‡
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1
Department of Digestive Surgery, Magellan Center, Bordeaux University Hospital, 33600 Pessac, France
2
Department of Digestive and Oncological Surgery, CHU Lille, Claude Huriez University Hospital, 59000 Lille, France
3
UMR-S 1172-CANTHER Laboratory “Cancer Heterogeneity, Plasticity and Resistance to Therapies”, University Lille, 59045 Lille, France
4
FFCD EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche-Comté, 21000 Dijon, France
5
Department of Digestive Oncology University Hospital Dijon, University of Burgundy and Franche Comté, 21000 Dijon, France
6
Federation Francophone de Cancérologie Digestive (FFCD), EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche Comté, 21000 Dijon, France
7
Department of Digestive Oncology, University Hospital, 63100 Clermont-Ferrand, France
8
Department of Oncology, University Hospital, 86000 Poitiers, France
9
Department of Gastroenterology, General Hospital, 74960 Annecy, France
10
Department of Gastroenterology, St Joseph General Hospital, 13000 Marseille, France
11
Department of Gastroenterology, Lyon Protestant Infirmary Clinic, 69300 Lyon, France
12
Department of Hepato-Gastroenterology, Saint Joseph Hospital, 13000 Marseille, France
13
Institut de Cancérologie de l’Ouest Paul Papin, 49000 Angers, France
14
Department of Hepato-Gastroenterology, Polyclinic Bordeaux Nord, 33000 Bordeaux, France
15
Medical Oncology, Clinique Tivoli Ducos, 33000 Bordeaux, France
16
Department of Hepato-Gastroenterology, Centre Hospitalier de Bourg en Bresse, 01053 Bourg-en-Bresse, France
17
Onco-Hematology Department, Centre Hospitalier du Mans, 72000 Le Mans, France
18
Radiotherapy and Oncology Department, Centre Hospitalier Bretagne Sud, 56100 Lorient, France
19
Department of Thoracic Surgery, North Hospital, Aix-Marseille University, 13000 Marseille, France
20
Service d’Oncologie Digestive, CHU Timone, 13000 Marseille, France
21
Hepato-Gastroenterology Unit, Meaux Hospital, 77100 Meaux, France
22
Gastroenterology, Centre Hospitalier de Mont-de-Marsan, 40000 Mont-de-Marsan, France
23
Iron Group, Normandy Centre for Genomic and Personalized Medicine and Department of Hepatogastroenterology, Rouen University Hospital, Normandie University, 76000 Rouen, France
24
Department of Oncology, Centre Paul Strauss, 67100 Strasbourg, France
25
Centre Hospitalier Universitaire de Toulouse, 31400 Toulouse, France
26
Department of Gastroenterology, CHU Nancy, 54500 Vandoeuvre-les-Nancy, France
27
Department of Digestive Oncology, CHU Reims, 51100 Reims, France
*
Author to whom correspondence should be addressed.
†
Christophe Mariette: deceased 18 July 2017.
‡
These authors contributed equally to this work.
Cancers 2023, 15(7), 2188; https://doi.org/10.3390/cancers15072188
Submission received: 19 February 2023
/
Revised: 31 March 2023
/
Accepted: 4 April 2023
/
Published: 6 April 2023
(This article belongs to the Special Issue New Trends in Esophageal Cancer Management)
Simple Summary
The treatment of resectable gastric and gastroesophageal junction adenocarcinomas is enhanced by a strategy of perioperative chemotherapy (CT) when compared with surgery alone. But, there is still a need for new approaches to further improve outcomes in patients treated with perioperative CT. Cetuximab, a human–murine chimeric monoclonal antibody binds with a high affinity to the EGFR binding site, and has shown activity against a variety of tumors, including G/GEJ adenocarcinomas. This study aimed to evaluate the efficacy and safety of perioperative cetuximab combined with 5-fluorouracil and cisplatin for the treatment of gastric and esophageal adenocarcinoma. The results of this phase two study showed safety but lack of efficacy regarding objective tumor response and absence of major toxicity.
Abstract
Purpose: While perioperative chemotherapy provides a survival benefit over surgery alone in gastric and gastroesophageal junction (G/GEJ) adenocarcinomas, the results need to be improved. This study aimed to evaluate the efficacy and safety of perioperative cetuximab combined with 5-fluorouracil and cisplatin. Patients and Methods: Patients received six cycles of cetuximab, cisplatin, and simplified LV5FU2 before and after surgery. The primary objective was a combined evaluation of the tumor objective response (TOR), assessed by computed tomography, and the absence of major toxicities resulting in discontinuation of neoadjuvant chemotherapy (NCT) (45% and 90%, respectively). Results: From 2011 to 2013, 65 patients were enrolled. From 64 patients evaluable for the primary endpoint, 19 (29.7%) had a morphological TOR and 61 (95.3%) did not stop NCT prematurely due to major toxicity. Sixty patients (92.3%) underwent resection. Sixteen patients (/56 available, 28.5%) had histological responses (Mandard tumor regression grade ≤3). After a median follow-up of 44.5 months, median disease-free and overall survival were 24.4 [95% CI: 16.4-39.4] and 40.3 months [95% CI: 27.5-NA], respectively. Conclusion: Adding cetuximab to the NCT regimen in operable G/GEJ adenocarcinomas is safe, but did not show enough efficacy in the present study to meet the primary endpoint (NCT01360086).
Keywords:
esogastric adenocarcinoma; neoadjuvant chemotherapy; cetuximab; surgery; efficacy; safety; EGFR-1
