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2022-RA-1294-ESGO Chemosensitivity in vulnerable older patients is unfavorable and highly dependent on the treatment regimen: CA125 elimination rate constant K (KELIM) analysis of the GINECO-ENGOT EWOC-1 trial
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  1. Olivier Colomban1,
  2. Emmanuelle Bourbouloux2,
  3. Marie-Ange Mouret-Renier3,
  4. Domenica Lorusso4,
  5. Cyriac Blonz5,
  6. Aude Marie Savoye6,
  7. Gilles Freyer7,
  8. Margot Noblecourt8,
  9. Michel Gatineau9,
  10. Laëtitia Stefani10,
  11. Laurence Gladieff11,
  12. Florence Joly12,
  13. Laurence Venat-Bouvet13,
  14. Delphine Mollon-Grange14,
  15. Ulla Peen15,
  16. Lucia Borgato16,17,
  17. Eric Pujade-Lauraine18,
  18. Benoit You19 and
  19. Claire Falandry20
  1. 1Université Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Sud, Lyon, France
  2. 2Institut de Cancérologie de l’Ouest (ICO), Saint-Herblain, France
  3. 3GINECO and Centre Jean Perrin, Clermont-Ferrand, France
  4. 4Multicentre Italian Trials in Ovarian cancer (MITO) and Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, and Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
  5. 5GINECO and Hôpital Privé du Confluent, Nantes, France
  6. 6GINECO and Institut Jean Godinot, Reims, France
  7. 7GINECO and Centre Hospitalier Lyon-Sud, Lyon, France
  8. 8GINECO and Centre Hospitalier de Cholet, Cholet, France
  9. 9GINECO and Groupe Hospitalier Saint-Joseph, Paris, France
  10. 10GINECO and Centre Hospitalier Annecy Genevois, Pringy, France
  11. 11GINECO and Institut Claudius Regaud IUCT-O, Toulouse, France
  12. 12GINECO and Centre François Baclesse, Caen, France
  13. 13GINECO and CHU de Limoges – Hôpital Dupuytren, Limoges, France
  14. 14GINECO and Centre Hospitalier Intercommunal de Cornouaille, Quimper, France
  15. 15Herlev Hospital and NSGO-CTU, Herlev, Denmark
  16. 16U.O.C. Oncologia AULSS3 Mirano – via D0n Giacobbe Sartor 4 30035 Mirano, Venice, Italy
  17. 17U.O.C Oncologia AULSS8 Vicenza, Vicenza, Italy
  18. 18ARCAGY-GINECO, Paris, France
  19. 19Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Université Lyon, CICLY and GINECO, Lyon, France
  20. 20Geriatrics, Hospices Civils de Lyon – Centre Hospitalier Lyon Sud, Saint-Genis-Laval, France

Abstract

Introduction/Background Older patients (pts) with ovarian cancer have a poorer survival, classically related to suboptimal treatment or excessive toxicities; however histological aggressivity and chemoresistance may contribute to this worse outcome. CA-125 elimination rate constant K (KELIM) was shown to be a robust marker of intrinsic chemosensitivity either in adjuvant or neoadjuvant settings. EWOC-1 trial (NCT02001272) was designed to evaluate the feasibility of three treatment regimens in vulnerable pts aged ≥70 years in first line; pts treated with carboplatin monotherapy (C) had a 2.79-fold higher risk of death compared to carboplatin-paclitaxel (CP). An ancillary analysis of EWOC-1 was designed to evaluate the differential chemosensitivity in the 3 treatment arms using KELIM.

Methodology KELIM calculation was performed according to You et al. (www.biomarker-kinetics.org™/CA125-neo) on EWOC-1 trial database of 120 pts (40 in each arm: standard CP (arm A); C (arm B); 3w/4 weekly CP (arm C)).

Results KELIM was evaluable for 58 pts (A: 18; B: 22; C: 18), its median [IQR] was 0.76 (0.59; 0.90) in the total population, significantly associated with treatment arms: A: 0.99 [0.71; 1.11]; B: 0.56 [0.32; 0.77]; C: 0.77 [0.50; 0.90], p=0.008; pairwise comparison arm A vs B, p=0.001. Only 15 pts (25.9%) had a favorable (≥1) KELIM, associated with a significant increase in overall survival (HR: 0.240; 95%CI: 0.089–0.645; p=0.002).

Conclusion KELIM values were globally unfavorable in this older population. Chemosensitivity was highly dependent on the treatment regimen, with a median KELIM comparable in the standard carboplatin-paclitaxel arm (A) to previously published data on younger patients. These data strengthen the need to avoid under-treatment in the older population. KELIMTM may be considered in older pts as both a marker of intrinsic- (tumor-related) and extrinsic-(treatment-related) chemosensitivity.

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