A phase II study of Navitoclax (ABT-263) as single agent in women heavily pretreated for recurrent epithelial ovarian cancer: The MONAVI - GINECO study

被引:15
|
作者
Joly, Florence [1 ,2 ]
Fabbro, Michel [3 ]
Follana, Philippe [4 ]
Lequesne, Justine [1 ]
Medioni, Jacques [5 ,16 ]
Lesoin, Anne [6 ]
Frenel, Jean-Sebastien [7 ]
Abadie-Lacourtoisie, Sophie [8 ]
Floquet, Anne [9 ]
Gladieff, Laurence [10 ]
You, Benoit [11 ,17 ]
Gavoille, Celine [12 ]
Kalbacher, Elsa [13 ]
Briand, Melanie [1 ,2 ]
Brachet, Pierre-Emmanuel [1 ,2 ]
Giffard, Florence [1 ,2 ]
Weiswald, Louis-Bastien [1 ,2 ]
Just, Pierre-Alexandre [14 ]
Blanc-Fournier, Cecile [1 ,2 ]
Leconte, Alexandra [1 ]
Clarisse, Benedicte [1 ]
Leary, Alexandra [15 ]
Poulain, Laurent [1 ,2 ]
机构
[1] UNICANCER, Ctr Francois Baclesse, 3 Ave Gen Harris, F-14000 Caen, France
[2] Normandie Univ, UNICAEN, INSERM U1086 ANTICIPE Interdisciplinary Res Unit, Ctr Francois Baclesse, 3 Ave Gen Harris, F-14000 Caen, France
[3] UNICANCER, Inst Canc Val dAurelle, 208 Rue Apothicaires, F-34298 Montpellier, France
[4] UNICANCER, Ctr Antoine Lacassagne, 33 Ave Valombrose, F-06189 Nice, France
[5] Hop Europeen Georges Pompidou, AP HP, 20 Rue Leblanc, F-75015 Paris, France
[6] UNICANCER, Ctr Oscar Lambret, 3 Rue Frederic Combemale, F-59000 Lille, France
[7] UNICANCER, Ctr Rene Gauducheau, Inst Cancerol Ouest, Blvd Projesseur Jacques Monad, F-44805 St Herblain, France
[8] UNICANCER, Ctr Paul Papin, Inst Cancerol Ouest, 15 Rue Bocquel, F-49055 Angers, France
[9] UNICANCER, Inst Bergonie, 229 Cours Argonne, F-33076 Bordeaux, France
[10] UNICANCER, Inst Univ Canc Toulouse Oncopole, Inst Claudius Regaud, 1 Ave Irene Joliot Curie, F-31059 Toulouse, France
[11] Ctr Hosp Lyon Sud, Inst Cancerol, Hosp Civils Lyon IC HCL, CITOHL, F-69310 Pierre Benite, France
[12] UNICANCER, Inst Cancerol Lorraine, 6 Ave Bourgogne Brabois, F-54511 Vandoeuvre Les Nancy, France
[13] Ctr Hosp Univ Jean Minjoz, 3 Blvd Alexandre Fleming, F-25030 Besancon, France
[14] Univ Paris, Cochin Hosp, AP HP, 27 Rue Faubourg St Jacques, F-75014 Paris, France
[15] UNICANCER, Inst Gustave Roussy, 39 Rue Camille Desmoulins, F-94805 Villejuif, France
[16] Univ Paris, UMR S1138 INSERM, UFR Med Paris Ctr, Paris, France
[17] Univ Claude Bernard Lyon 1, EA3738 CICLY, UCBL, Lyon, France
关键词
Ovarian cancer; BH3; mimetics; Platinum resistance; Early phase study; PEGYLATED LIPOSOMAL DOXORUBICIN; PACLITAXEL-RESISTANT OVARIAN; PLATINUM-RESISTANT; OPEN-LABEL; CARCINOMA CELLS; FAMILY INHIBITOR; BEVACIZUMAB; BCL-2; COMBINATION; TRIAL;
D O I
10.1016/j.ygyno.2022.01.021
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background. There are limited treatment options for ovarian cancer patients with early relapse after platinum chemotherapy. In preclinical studies, we previously demonstrated the promising activity of ABT-737, a Bcl-2/Bcl-xL anti-apoptotic protein inhibitor, in chemo-resistant ovarian cancer cells and tumors, suggesting its potential activity in platinum-resistant patients. Methods. We conducted a prospective multicenter single-arm phase II study to assess the efficacy of Navitoclax (orally available ABT-737 analogue) monotherapy in 46 heavily pretreated (2-12 lines, median = 4) patients with high-grade serous platinum-resistant ovarian tumors. Navitoclax was administered at the daily dose of 150 mg during a lead-in period (7-14 days) and then increased to 250 mg daily in the absence of dose-limiting thrombocytopenia (<G3). Progression-free survival (PFS) based on RECIST v1.1 criteria was the primary endpoint. Analysis of efficacy according to the expression of Bcl-2 family proteins in tumor biopsies was also planned. Results. The 3-month PFS was 22.7% [ 95%CI: 13.2-39.2], median PFS was 1.64 months [ 95%CI: 1.58-2.30]. There were 16 (35.6%, 95%CI: 22.3-51.3) overall responses (RECIST v1.1): 1 partial response and 15 stable diseases. No correlation between the expression of Bim, Mcl-1 and P-ERK with clinical response was found in this study. Thrombocytopenia was the major side-effect (G3/4: n=12; 26%), leading to pursue at the daily dose of 150 mg in 8 patients and to discontinue treatment in 3 patients. Neither significant bleeding nor toxic death were observed. Conclusions. Navitoclax monotherapy had poor activity that was not correlated with the expression of Bim, Mcl-1 and P-ERK, without unacceptable toxicity. (C) 2022 Elsevier Inc. All rights reserved.
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页码:30 / 39
页数:10
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