Roman Rouzier1, Sébastien Gouy2, Frédéric Selle3, Eric Lambaudie4, Anne Floquet5, Virginie Fourchotte6, Christophe Pomel7, Pierre-Emmanuel Colombo8, Elsa Kalbacher9, Sandrine Martin-Francoise10, Raffaele Fauvet11, Philippe Follana12, Anne Lesoin13, Fabrice Lecuru14, Youssef Ghazi15, Julien Dupin16, Elisabeth Chereau4, Sarah Zohar17, Paul Cottu6, Florence Joly18. 1. Institut Curie, Saint-Cloud-Paris, UNiversité Versailles-Saint-Quentin, France. Electronic address: roman.rouzier@curie.fr. 2. Institut Gustave Roussy, Villejuif, France. 3. GHU-Est Tenon, Paris, France. 4. Institut Paoli-Calmettes, Marseille, France. 5. Institut Bergonié, Bordeaux, France. 6. Institut Curie, Saint-Cloud-Paris, UNiversité Versailles-Saint-Quentin, France. 7. Centre Jean Perrin, Clermont-Ferrand, France. 8. Institut régional du Cancer de Montpellier, Val d'Aurelle, Montpellier, France. 9. CHU Besançon, Besançon, France. 10. Centre François Baclesse, Caen, France. 11. CHU Amiens, Amiens, France. 12. Centre Antoine Lacassagne, Nice, France. 13. Centre Oscar Lambret, Lille, France. 14. European Hospital George Pompidou, Paris, France. 15. Roche, Boulogne-Billancourt, France. 16. ITM stat for Roche, Boulogne-Billancourt, France. 17. Centre de Recherche des Cordeliers, Université Paris 5, Université Paris 6, Paris, France. 18. Centre François Baclesse, Caen, France. Electronic address: f.joly@baclesse.unicancer.fr.
Abstract
AIM: To investigate whether adding bevacizumab to neoadjuvant carboplatin-paclitaxel (CP) helps achieve optimal debulking, measured by complete resection rate (CRR) at interval debulking surgery (IDS), in patients with initially unresectable International Federation of Gynecology and Obstetrics stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma. METHODS: Multicentre, open-label, non-comparative phase II study. Ninety-five patients randomised (2:1) to receive four cycles of neoadjuvant CP ±3 concomitant cycles of bevacizumab 15 mg/kg (BCP) followed by IDS. Primary objective is to evaluate the CRR at IDS in the BCP group (reference CRR rate defined as 45% CRR). A stopping rule based on bevacizumab-related adverse events (AEs) of special interest was implemented. RESULTS: In the BCP group (N = 58), IDS was performed in 40 (69%) patients, of whom 85% had a complete resection. The CRR of this group was therefore 58.6% (34 patients), statistically over pre-defined 45%. The CRR in the CP group was 51.4%: 22 (60%) patients underwent IDS (85% had a complete resection). Grade ≥3 adverse events occurred in 62% of the BCP-treated patients and 63% of the CP-treated patients: mainly blood and lymphatic, gastrointestinal and vascular disorders, without more toxicity with BCP. Postoperative complications (mainly wound, infectious and gastrointestinal complications) occurred in 28% and 36% of the patients, respectively. The pre-specified safety stopping rule was not reached. CONCLUSION: The primary objective was met as the CRR with BCP was significantly higher than the reference rate. Bevacizumab may be safely added to a preoperative program in patients deemed non-optimally resectable, whatever the final surgical decision. Bevacizumab's role in this setting should be further investigated.
RCT Entities:
AIM: To investigate whether adding bevacizumab to neoadjuvant carboplatin-paclitaxel (CP) helps achieve optimal debulking, measured by complete resection rate (CRR) at interval debulking surgery (IDS), in patients with initially unresectable International Federation of Gynecology and Obstetrics stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma. METHODS: Multicentre, open-label, non-comparative phase II study. Ninety-five patients randomised (2:1) to receive four cycles of neoadjuvant CP ±3 concomitant cycles of bevacizumab 15 mg/kg (BCP) followed by IDS. Primary objective is to evaluate the CRR at IDS in the BCP group (reference CRR rate defined as 45% CRR). A stopping rule based on bevacizumab-related adverse events (AEs) of special interest was implemented. RESULTS: In the BCP group (N = 58), IDS was performed in 40 (69%) patients, of whom 85% had a complete resection. The CRR of this group was therefore 58.6% (34 patients), statistically over pre-defined 45%. The CRR in the CP group was 51.4%: 22 (60%) patients underwent IDS (85% had a complete resection). Grade ≥3 adverse events occurred in 62% of the BCP-treated patients and 63% of the CP-treated patients: mainly blood and lymphatic, gastrointestinal and vascular disorders, without more toxicity with BCP. Postoperative complications (mainly wound, infectious and gastrointestinal complications) occurred in 28% and 36% of the patients, respectively. The pre-specified safety stopping rule was not reached. CONCLUSION: The primary objective was met as the CRR with BCP was significantly higher than the reference rate. Bevacizumab may be safely added to a preoperative program in patients deemed non-optimally resectable, whatever the final surgical decision. Bevacizumab's role in this setting should be further investigated.
Authors: Andres Redondo; Ana Oaknin; Maria Jesus Rubio; Maria-Pilar Barretina-Ginesta; Ana de Juan; Luis Manso; Ignacio Romero; Cristina Martin-Lorente; Andres Poveda; Antonio Gonzalez-Martin Journal: J Ovarian Res Date: 2021-05-26 Impact factor: 4.234
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