44 results on '"Selle F"'
Search Results
2. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial
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Ray-Coquard, I., Leary, A., Pignata, S., Cropet, C., González-Martín, A., Marth, C., Nagao, S., Vergote, I., Colombo, N., Mäenpää, J., Selle, F., Sehouli, J., Lorusso, D., Guerra Alia, E.M., Bogner, G., Yoshida, H., Lefeuvre-Plesse, C., Buderath, P., Mosconi, A.M., Lortholary, A., Burges, A., Medioni, J., El-Balat, A., Rodrigues, M., Park-Simon, T.-W., Dubot, C., Denschlag, D., You, B., Pujade-Lauraine, E., and Harter, P.
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- 2023
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3. 19P Long-term fatigue after treatments for non-epithelial ovarian cancer survivors
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Dubot, C., primary, Ray-Coquard, I.L., additional, Pautier, P., additional, Lequesne, J., additional, Renaud, T., additional, Selle, F., additional, Berton-Rigaud, D., additional, Frank, S., additional, De La Motte Rouge, T., additional, Kalbacher, E., additional, Gross, M. Provansal, additional, Blonz, C., additional, Orfeuvre, H., additional, Alexandre, J., additional, Augereau, P., additional, Kurtz, J.E., additional, Grellard, J-M., additional, Clarisse, B., additional, Gernier, F., additional, and Lobbedez, F. Joly, additional
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- 2024
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4. 20P Deciphering tumor microenvironment heterogeneity between primary tumor and metastases in high grade serous ovarian cancer (HGSC) to predict response to immunotherapy (IT): Analyses from the NeoPembrOv/GINECO phase II trial
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Collet, L., primary, Ardin, M., additional, Venet, D., additional, Berthet, J., additional, Treilleux, I., additional, Leheurteur, M., additional, Meunier, J., additional, Lefevre, L. Bengrine, additional, Martinez, M., additional, Priou, F., additional, Selle, F., additional, Just, P-A., additional, Bataillon, G., additional, Rothé, F., additional, Sotiriou, C., additional, Dubois, B., additional, Caux, C., additional, Ray-Coquard, I.L., additional, and Le Saux, O., additional
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- 2023
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5. LBA42 Olaparib vs placebo as maintenance therapy after platinum-based chemotherapy in advanced/metastatic endometrial cancer patients: The GINECO randomized phase IIb UTOLA trial
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Joly Lobbedez, F., primary, Leary, A., additional, Ray-Coquard, I.L., additional, Asselain, B., additional, Rodrigues, M.J., additional, Gladieff, L., additional, Bazan, F., additional, Abadie Lacourtoisie, S., additional, Lebreton, C., additional, Bengrine Lefevre, L., additional, Leroy, K., additional, Leman, R., additional, Fournel, P., additional, Largillier, R., additional, Selle, F., additional, Frenel, J-S., additional, Fernandez, Y., additional, Foa, C., additional, You, B., additional, and Alexandre, J., additional
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- 2023
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6. 815P Clinical outcome of metastatic endometrial carcinoma patients treated with chemotherapy: ENDOVIE, a GINECO national observational cohort study
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Alexandre, J., primary, Boudier, P., additional, Kalbacher, E., additional, Asselain, B., additional, Lavit, E., additional, Emambux, S., additional, Berton-Rigaud, D., additional, Babin, G., additional, Lescure, C., additional, Heudel, P-E., additional, Salaun, H., additional, Delanoy, N., additional, Dawood, H., additional, Combe, P-F., additional, Duliege, D., additional, Selle, F., additional, Hakme, A., additional, Cagnan, L., additional, Niogret, J., additional, and De Percin, S., additional
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- 2023
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7. 34O ATR inhibitor alone (ceralasertib) or in combination with olaparib in gynaecological cancers with ARID1A loss or no loss: Results from the ENGOT/GYN1/NCRI ATARI trial
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Banerjee, S., primary, Leary, A., additional, Stewart, J.R., additional, Dewan, M., additional, Lheureux, S., additional, Clamp, A.R., additional, Ray-Coquard, I.L., additional, Selle, F., additional, Gourley, C., additional, Glasspool, R.M., additional, Bowen, R., additional, Attygalle, A., additional, Vroobel, K., additional, Tunariu, N., additional, Wilkinson, K., additional, Toms, C., additional, Natrajan, R., additional, Bliss, J., additional, Lord, C., additional, and Porta, N., additional
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- 2023
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8. 19P Long term sexual disorders among rare ovarian cancer survivors: The national GINECO case-control Vivrovaire Rare Tumors study
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Dubot, C., primary, Joly Lobbedez, F., additional, Ray Coquard, I.L., additional, Floquet, A., additional, Lefevre Arbogast, S., additional, Selle, F., additional, Berton-Rigaud, D., additional, Frank, S., additional, De La Motte Rouge, T., additional, Kalbacher, E., additional, Provansal Gross, M., additional, Lortholary, A., additional, Orfeuvre, H., additional, Alexandre, J., additional, Augereau, P., additional, Nadeau, C., additional, Kurtz, J.E., additional, Grellard, J-M., additional, Pautier, P., additional, and Gernier, F., additional
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- 2023
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9. 13O Impact of surgery and chemotherapy in ovarian sex cord-stromal tumors from the multicentric Salomé study including 469 patients: A TMRG and GINECO group study
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Hanvic, B., primary, Lecuru, F., additional, Vanacker, H., additional, Pautier, P., additional, Narducci, F., additional, Cherifi, F., additional, Floquet, A., additional, Angeles, M.A., additional, Berton-Rigaud, D., additional, Pomel, C., additional, Kalbacher, E., additional, Provansal Gross, M., additional, Fernandez, Y., additional, De La Motte Rouge, T., additional, Selle, F., additional, Meeus, P., additional, Genestie, C., additional, Salleron, J., additional, and Ray-Coquard, I.L., additional
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- 2023
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10. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial
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Ray-Coquard, I, Leary, A, Pignata, S, Cropet, C, González-Martin, A, Marth, C, Nagao, S, Vergote, I, Colombo, N, Mäenpää, J, Selle, F, Sehouli, J, Lorusso, D, Alia, E, Bogner, G, Yoshida, H, Lefeuvre-Plesse, C, Buderath, P, Mosconi, A, Lortholary, A, Burges, A, Medioni, J, El-Balat, A, Rodrigues, M, Park-Simon, T, Dubot, C, Denschlag, D, You, B, Pujade-Lauraine, E, Harter, P, Alia, E M Guerra, Mosconi, A M, Park-Simon, T-W, Ray-Coquard, I, Leary, A, Pignata, S, Cropet, C, González-Martin, A, Marth, C, Nagao, S, Vergote, I, Colombo, N, Mäenpää, J, Selle, F, Sehouli, J, Lorusso, D, Alia, E, Bogner, G, Yoshida, H, Lefeuvre-Plesse, C, Buderath, P, Mosconi, A, Lortholary, A, Burges, A, Medioni, J, El-Balat, A, Rodrigues, M, Park-Simon, T, Dubot, C, Denschlag, D, You, B, Pujade-Lauraine, E, Harter, P, Alia, E M Guerra, Mosconi, A M, and Park-Simon, T-W
- Abstract
Background: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status. Patients and methods: Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis. Results: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms. Conclusions: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified expl
- Published
- 2023
11. 176O Final overall survival (OS) results from the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC)
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Nagao, S., primary, Harter, P., additional, Leary, A., additional, Cropet, C., additional, Pignata, S., additional, Fujiwara, K., additional, Gonzalez Martin, A.J., additional, Bogner, G., additional, Vergote, I., additional, Colombo, N., additional, Maenpaa, J., additional, Selle, F., additional, Schmalfeldt, B., additional, Scambia, G., additional, Guerra Alia, E.M., additional, Lefeuvre-Plesse, C., additional, Belau, A., additional, Lortholary, A., additional, Gropp-Meier, M., additional, Pujade-Lauraine, E., additional, and Ray-Coquard, I., additional
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- 2022
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12. LBA30 Phase III ATALANTE/ov29 trial: Atezolizumab (Atz) versus placebo with platinum-based chemotherapy (Cx) plus bevacizumab (bev) in patients (pts) with platinum-sensitive relapse (PSR) of epithelial ovarian cancer (OC)
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Kurtz, J.E., primary, Pujade-Lauraine, E., additional, Oaknin, A., additional, Belin, L., additional, Tsibulak, I., additional, Cibula, D., additional, Vergote, I.B., additional, Rosengarten, O.S., additional, Rodrigues, M.J., additional, de Gregorio, N., additional, Martinez-Garcia, J., additional, Pautier, P., additional, Mouret Reynier, M.A., additional, Selle, F., additional, D'Hondt, V., additional, Lobbedez, F. Joly, additional, Boissier, E. Bultot, additional, Floquet, A., additional, Heudel, P-E., additional, and Heitz, F., additional
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- 2022
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13. 1577P Optimizing the management of PARP inhibitors in clinical practice: Results of a DELPHI French consensus
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Selle, F., primary, Scotté, F., additional, Boffa, J-J., additional, Etienne, G., additional, Angelergues, A., additional, Augereau, P., additional, Berton-Rigaud, D., additional, Dielenseger, P., additional, Fabbro, M., additional, Falandry, C., additional, Follana, P., additional, Gladieff, L., additional, Joly Lobbedez, F., additional, Kurtz, J.E., additional, Matta, C., additional, Mouret Reynier, M.A., additional, Schmitt, A., additional, Marjollet, C., additional, and Floquet, A., additional
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- 2022
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14. LBA29 Final overall survival (OS) results from the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC)
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Ray-Coquard, I.L., primary, Leary, A., additional, Pignata, S., additional, Cropet, C., additional, Martin, A.J. Gonzalez, additional, Bogner, G., additional, Yoshida, H., additional, Vergote, I.B., additional, Colombo, N., additional, Maenpaa, J., additional, Selle, F., additional, Schmalfeldt, B., additional, Scambia, G., additional, Alia, E.M. Guerra, additional, Lefeuvre-Plesse, C., additional, Belau, A., additional, Lortholary, A., additional, Gropp-Meier, M., additional, Pujade-Lauraine, E., additional, and Harter, P., additional
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- 2022
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15. 177 Efficacy of niraparib by timing of surgery and residual disease: a post-hoc analysis of patients in the PRIMA/ENGOT-OV26/GOG-3012 study
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O’cearbhaill, R, primary, Pérez-Fidalgo, JA, additional, Monk, BJ, additional, Vulsteke, C, additional, Mccormick, C, additional, Hietanen, S, additional, Moore, RG, additional, Artioli, G, additional, Shahin, MS, additional, Selle, F, additional, Bradley, WH, additional, Baumann, K, additional, O’malley, D, additional, Tusquets, I, additional, Slomovitz, BM, additional, Levy, T, additional, Joly, F, additional, Malinowska, I, additional, Gupta, D, additional, and González-Martin, A, additional
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- 2021
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16. 1196 A randomised phase II study of combination chemotherapy with nintedanib/placebo in advanced/recurrent endometrial cancer. FANDANGO/ENGOT-EN1/FANDANGO
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Mirza, M, primary, Berton, D, additional, Vergote, I, additional, Depont Christensen, R, additional, Floquet, A, additional, Maenpaa, J, additional, Braicu, I, additional, Altintas, S, additional, Follana, P, additional, Ør Knudsen, A, additional, Ataseven, B, additional, Selle, F, additional, Lundgren, C, additional, Huober, J, additional, Fabbro, M, additional, Denys, H, additional, Heudel, P, additional, Magnusson, M, additional, Lindemann, K, additional, and Sehouli, J, additional
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- 2021
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17. LBA37 Atezolizumab (atezo) combined with platinum-based chemotherapy (CT) and maintenance niraparib for recurrent ovarian cancer (rOC) with a platinum-free interval (TFIp) >6 months: Primary analysis of the double-blind placebo (pbo)-controlled ENGOT-Ov41/GEICO 69-O/ANITA phase III trial
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Gonzalez Martin, A., Rubio Perez, M.J., Heitz, F., Christensen, R.D., Colombo, N., Van Gorp, T., Oaknin, A., Leary, A., Gaba Garcia, L., Lebreton, C., De Sande González, L.M., Romeo Marin, M., Redondo, A., Barretina Ginesta, M.P., Perez Fidalgo, J.A., Santaballa Bertran, A., Bermejo-Pérez, M.J., Bruchim, I., Ray-Coquard, I.L., and Selle, F.
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- 2023
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18. 747MO First results from the ENGOT-GYN2/GOG-3051/BOUQUET phase II biomarker-directed platform study: Cobimetinib (cobi) or atezolizumab (atezo) + bevacizumab (bev) for persistent/recurrent rare epithelial ovarian cancer (eOC)
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Ray-Coquard, I.L., Pignata, S., Lee, J-Y., Coleman, R.L., Brown, J., Kim, J-W., Selle, F., Lorusso, D., Bermejo-Pérez, M.J., Pautier, P., Gourley, C., Ayhan, A., Richardson, G., Cibula, D., Yauch, L., Dieterich, M., Krishnan, V., Calas-Zeroug, O., Harter, P., and Gershenson, D.M.
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- 2023
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19. 535P Long term quality of life after chemotherapy among nonepithelial ovarian cancer survivors: The case-control vivrovaire rare tumours study
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Joly Lobbedez, F., Ray-Coquard, I.L., Lefevre Arbogast, S., Grellard, J-M., Clarisse, B., Floquet, A., Selle, F., Berton-Rigaud, D., Frank, S., De La Motte Rouge, T., Kalbacher, E., Provansal Gross, M., A. lortholary, Orfeuvre, H., Alexandre, J., Augereau, P., Kurtz, J.E., Nadeau, C., Pautier, P., and Gernier, F.
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- 2022
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20. 761P Anti-angiogenic therapy in first-line treatment of low-grade serous ovarian cancer: Exploratory meta-analysis of the prospective AGO-OVAR 11/12/16 studies.
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Czogalla, B., Trillsch, F., Heitz, F., Mahner, S., Loidl, V., Aminossadati, B., Malander, S., de Gregorio, N., Selle, F., Wimberger, P., Mirza, M.R., Sehouli, J., Lortholary, A., Baumann, K.H., Hilpert, F., Canzler, U., Hanker, L.C., Pfisterer, J., Harter, P., and du Bois, A.
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NEOVASCULARIZATION inhibitors , *OVARIAN cancer , *THERAPEUTICS - Published
- 2024
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21. 730P Validation of circulating tumor DNA for prognostication and monitoring in metastatic endometrial carcinoma: Ancillary results from the phase II randomized GINECO trial UTOLA.
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Beinse, G., Taly, V., Leary, A., Baures, A., Tredan, O., You, B., Rodrigues, M.J., Gladieff, L., Lacourtoisie, S. Abadie, Lefevre, L. Bengrine, Brachet, P-E., Lebreton, C., Kalbacher, E., Fournel, P., Frenel, J-S., Selle, F., Largillier, R., Laurent-Puig, P., Lobbedez, F. Joly, and Alexandre, J.
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CIRCULATING tumor DNA , *ENDOMETRIAL cancer , *METASTASIS - Published
- 2024
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22. Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer.
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Harter, P., Sehouli, J., Vergote, I., Ferron, G., Reuss, A., Meier, W., Greggi, S., Mosgard, B. J., Selle, F., Guyon, F., Pomel, C., Lécuru, F., Zang, R., Avall-Lundqvist, E., Kim, J.-W., Ponce, J., Raspagliesi, F., Kristensen, G., Classe, J.-M., and Hillemanns, P.
- Abstract
BACKGROUND Treatment for patients with recurrent ovarian cancer has been mainly based on desystemic therapy. The role of secondary cytoreductive surgery is unclear. METHODS We randomly assigned patients with recurrent ovarian cancer who had a first relapse after a platinum-free interval (an interval during which no platinum-based chemotherapy was used) of 6 months or more to undergo secondary cytoreductive surgery and then receive platinum-based chemotherapy or to reCeive platinum-Supplemenbased chemotherapy alone. Patients were eligible if they presented with a positive Arbeitsgemeinschaft GynUkologische Onkologie (AGO) score, defined as an Eastern Cooperative Oncology Group performance-status score of 0 (on a 5-point scale, with higher scores indicating greater disability), ascites of less than 500 ml, and complete resection at initial surgery. A positive AGO score is used to identify patients in whom a complete resection might be achieved. The primary end point was overall survival. We also assessed quality of life and prognostic factors for survival. RESULTS A total of407 patients underwent randomization: 206 were assigned to cytoreductive surgery and chemotherapy, and 201 to chemotherapy alone. A complete resection was achieved in 75.5% of the patients in the surgery group who underwent the procedure. The median overall survival was 53.7 months in the surgery group and 46.0 months in the no-surgery group (hazard ratio for death, 0.75; 95% confidence interval, 0.59 to 0.96; P=0.02). Patients with a complete resection had the most favorable outcome, with a median overall survival of 61.9 months. A benefit from surgery was seen in all analyses in subgroups according to prognostic factors. Quality-ofllife measures through 1 year of follow-up did not differ between the two groups, and we observed no perioperative mortality within 30 days after surgery. CONCLUSIONS In women with recurrent ovarian cancer, cytoreductive surgery followed by chemotherapy resulted in longer overall survival than chemotherapy alone. (Funded by the AGO Study Group and others; DESKTOP III ClinicalTrials.gov number, NCT0116673Z). [ABSTRACT FROM AUTHOR]
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- 2021
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23. Olaparib plus bevacizumab first-line maintenance in ovarian cancer : final overall survival results from the PAOLA-1/ENGOT-ov25 trial
- Author
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I. Ray-Coquard, A. Leary, S. Pignata, C. Cropet, A. González-Martin, C. Marth, S. Nagao, I. Vergote, N. Colombo, J. Mäenpää, F. Selle, J. Sehouli, D. Lorusso, E.M. Guerra Alia, G. Bogner, H. Yoshida, C. Lefeuvre-Plesse, P. Buderath, A.M. Mosconi, A. Lortholary, A. Burges, J. Medioni, A. El-Balat, M. Rodrigues, T.-W. Park-Simon, C. Dubot, D. Denschlag, B. You, E. Pujade-Lauraine, P. Harter, Ray-Coquard, I, Leary, A, Pignata, S, Cropet, C, González-Martin, A, Marth, C, Nagao, S, Vergote, I, Colombo, N, Mäenpää, J, Selle, F, Sehouli, J, Lorusso, D, Alia, E, Bogner, G, Yoshida, H, Lefeuvre-Plesse, C, Buderath, P, Mosconi, A, Lortholary, A, Burges, A, Medioni, J, El-Balat, A, Rodrigues, M, Park-Simon, T, Dubot, C, Denschlag, D, You, B, Pujade-Lauraine, E, and Harter, P
- Subjects
Oncology ,advanced ovarian cancer ,overall survival ,Medizin ,Hematology ,bevacizumab ,olaparib - Abstract
Background: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status. Patients and methods: Patients were randomized 2: 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis. Results: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms. Conclusions: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high proportion of patients in the placebo arm receiving poly(ADP-ribose) polymerase inhibitors after progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure. in press
- Published
- 2023
24. Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer
- Author
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Kathleen N. Moore, Alexandra Leary, Dominique Berton, Christina P. Opperman, Maria Del Pilar Estevez-Diz, Laurence Gladieff, Marek Ancukiewicz, Anne-Claire Hardy-Bessard, Frédéric Selle, Isabelle Ray-Coquard, Waldo Ortuzar Feliu, Carlos Rojas, Bradley J. Monk, David M. O'Malley, Ana Oaknin, Carla Rameri Alexandre Silva de Azevedo, Leslie M Randall, Jérôme Alexandre, Institut Català de la Salut, [O'Malley DM] The Ohio State University, James Comprehensive Cancer Center, Columbus, OH, United States. [Oaknin A] Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Monk BJ] Arizona Oncology (US Oncology Network), Creighton University School of Medicine, Phoenix, AZ, United States. [Selle F] Groupe Hospitalier Diaconesses-Croix Saint Simon, Paris, France. [Rojas C] Centro de Investigacion Clinica, Bradford Hill, Santiago, Chile. [Gladieff L] Institut Claudius Regaud-Institut Universitaire du Cancer (IUCT)-Oncopole, Toulouse, France, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Adult ,Diarrhea ,medicine.medical_specialty ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Uterine Cervical Neoplasms ,Phases of clinical research ,Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Uterine Cervical Neoplasms [DISEASES] ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Drug Administration Schedule ,Coll uterí - Càncer - Tractament ,Internal medicine ,Clinical endpoint ,Humans ,Medicine ,Infusions, Intravenous ,Adverse effect ,Immune Checkpoint Inhibitors ,Response Evaluation Criteria in Solid Tumors ,Aged ,Aged, 80 and over ,Enterocolitis ,Cervical cancer ,business.industry ,Obstetrics and Gynecology ,Immunotherapy ,Middle Aged ,medicine.disease ,Progression-Free Survival ,Clinical trial ,Oncology ,Medicaments - Eficàcia ,Avaluació de resultats (Assistència sanitària) ,Female ,Neoplasm Recurrence, Local ,medicine.symptom ,business ,neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales femeninos::neoplasias uterinas::neoplasias del cuello uterino [ENFERMEDADES] - Abstract
Cervical cancer; Checkpoint inhibitor; Immunotherapy Cáncer de cuello uterino; Inhibidor de puntos de control; Inmunoterapia Càncer cervical; Inhibidor de punts de control; Immunoteràpia Objective This phase II clinical trial evaluated the safety and antitumor activity of balstilimab, an anti-PD-1 antibody, in patients with previously-treated, recurrent/metastatic cervical cancer. Methods Eligible patients were 18 years or older with recurrent and/or metastatic cervical cancer and who had relapsed after a prior platinum-based treatment regimen for advanced disease. Balstilimab was administered intravenously at 3 mg/kg once every two weeks, for up to 24 months. The primary endpoint was objective response rate (ORR, RECIST v1.1) as assessed by an independent review committee. Results At data cutoff, 161 women (median age, 53 years [range 25–81]) were enrolled and treated with balstilimab. Of these, 140 had measurable disease at baseline and one prior line of platinum-based therapy in the metastatic, persistent, or recurrent setting; these patients were included in the efficacy analyses. The ORR was 15% (95% CI, 10.0%–21.8%) and included 5 patients with a complete response and 16 with a partial response. The median duration of response was 15.4 months. In patients with PD-L1-positive tumors the ORR was 20%, however patients with PD-L1-negative tumors also responded to balstilimab (ORR, 7.9%). Responses were not restricted to tumors of squamous cell histology, and an ORR of 12.5% was seen in the subset of patients with cervical adenocarcinoma. The disease control rate was 49.3% (95% CI, 41.1%–57.5%). Immune-mediated enterocolitis (3.1%) and diarrhea (1.9%) were the most common grade 3 or higher treatment-related adverse events. Conclusion Balstilimab demonstrated meaningful and durable clinical activity, with manageable safety, in patients with previously-treated, recurrent/metastatic cervical cancer. This study was funded by Agenus Inc.
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- 2021
25. Atezolizumab Combined With Platinum and Maintenance Niraparib for Recurrent Ovarian Cancer With a Platinum-Free Interval >6 Months: ENGOT-OV41/GEICO 69-O/ANITA Phase III Trial.
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González-Martín A, Rubio MJ, Heitz F, Depont Christensen R, Colombo N, Van Gorp T, Romeo M, Ray-Coquard I, Gaba L, Leary A, De Sande LM, Lebreton C, Redondo A, Fabbro M, Barretina Ginesta MP, Follana P, Pérez-Fidalgo JA, Rodrigues M, Santaballa A, Sabatier R, Bermejo-Pérez MJ, Lotz JP, Pardo B, Marquina G, Sánchez-Lorenzo L, Quindós M, Estévez-García P, Guerra Alía E, Manso L, Casado V, Kommoss S, Tognon G, Henry S, Bruchim I, Oaknin A, and Selle F
- Abstract
Purpose: To evaluate atezolizumab combined with platinum-based chemotherapy (CT) followed by maintenance niraparib for late-relapsing recurrent ovarian cancer., Methods: The multicenter placebo-controlled double-blind randomized phase III ENGOT-OV41/GEICO 69-O/ANITA trial (ClinicalTrials.gov identifier: NCT03598270) enrolled patients with measurable high-grade serous, endometrioid, or undifferentiated recurrent ovarian cancer who had received one or two previous CT lines (most recent including platinum) and had a treatment-free interval since last platinum (TFIp) of >6 months. Patients were stratified by investigator-selected carboplatin doublet, TFIp, BRCA status, and PD-L1 status in de novo biopsy and randomly assigned 1:1 to receive either atezolizumab or placebo throughout standard therapy comprising six cycles of a carboplatin doublet followed (in patients with response/stable disease) by maintenance niraparib until progression. The primary end point was investigator-assessed progression-free survival (PFS) per RECIST v1.1., Results: Between November 2018 and January 2022, 417 patients were randomly assigned (15% BRCA- mutated, 36% PD-L1-positive, 66% TFIp >12 months, 11% previous poly [ADP-ribose] polymerase inhibitor after frontline CT, and 53% previous bevacizumab). Median follow-up was 28.6 months (95% CI, 26.6 to 30.5 months). Atezolizumab did not significantly improve PFS (hazard ratio, 0.89 [95% CI, 0.71 to 1.10]; P = .28). Median PFS was 11.2 months (95% CI, 10.1 to 12.1 months) with atezolizumab versus 10.1 months (95% CI, 9.2 to 11.2 months) with standard therapy. Subgroup analyses generally showed consistent results, including analyses by PD-L1 status. The objective response rate (ORR) was 45% (95% CI, 39 to 52) with atezolizumab and 43% (95% CI, 36 to 49) with standard therapy. The safety profile was as expected from previous experience of these drugs., Conclusion: Combining atezolizumab with CT and maintenance niraparib for late-relapsing recurrent ovarian cancer did not significantly improve PFS or the ORR.
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- 2024
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26. Clinical and radiological pattern of olaparib-induced interstitial lung disease.
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Brudon A, Fournier D, Selle F, Seront E, Conforti R, Veyrac G, Gouraud A, Lebrun-Vignes B, Khalil A, Zalcman G, and Gounant V
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- Humans, Female, Retrospective Studies, Aged, Middle Aged, Adult, Breast Neoplasms drug therapy, Tomography, X-Ray Computed, Ovarian Neoplasms drug therapy, France, Belgium, Lung Diseases, Interstitial chemically induced, Lung Diseases, Interstitial diagnostic imaging, Phthalazines adverse effects, Phthalazines therapeutic use, Piperazines adverse effects, Piperazines therapeutic use, Pharmacovigilance, Poly(ADP-ribose) Polymerase Inhibitors adverse effects, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use
- Abstract
Background: PARP inhibitors (PARPi) are used in the treatment of ovarian, breast, pancreatic, and prostate cancers. Pneumonitis has been identified as a potential side effect, with a higher meta-analysis-assessed risk for olaparib versus other PARPi. Olaparib-induced interstitial lung disease (O-ILD) was first described within the Japanese population, with few information available for Caucasian patients., Methods: We performed a retrospective study by pooling data from the French and Belgian pharmacovigilance databases from 2018 to 2022. Patients with O-ILD were included following a central review by: 1) pharmacologists using the French drug causality assessment method; 2) senior pneumologists or radiologists, using the Fleischner Society's recommendations., Results: Five patients were identified and analysed. All were females, with ovarian or breast cancer. Median age at O-ILD diagnosis was 71 (38-72) years old, with no smoking history. Median delay between treatment initiation and symptom occurrence was 12 (6-33) weeks. Pneumonitis severity assessed using the Common Terminology Criteria for Adverse Events V5 was Grade 3 (n = 4) or 2 (n = 1). CT-scan review (n = 3) described hypersensitivity pneumonitis reaction as a common pattern. Bronchioalveolar lavage (n = 4) revealed lymphocytic alveolitis. Treatments relied on olaparib discontinuation (n = 5) and glucocorticoid intake (n = 4), with no fatal issue. Safe re-challenge with PARPi occurred in two patients. Forty additional O-ILD cases were identified in the WHO VigiBase database, including one fatal case., Conclusions: PARPi-ILD is a rare but potentially life-threatening disease, presenting as a hypersensitivity pneumonitis pattern within 3 months of PARPi initiation. Treatment primarily relies on medication discontinuation. Re-challenging with another PARPi could be considered., Clinical Trial Number: CEPRO #2023-010., (© 2024. The Author(s).)
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- 2024
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27. Neoadjuvant and adjuvant pembrolizumab in advanced high-grade serous carcinoma: the randomized phase II NeoPembrOV clinical trial.
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Ray-Coquard IL, Savoye AM, Schiffler C, Mouret-Reynier MA, Derbel O, Kalbacher E, LeHeurteur M, Martinez A, Cornila C, Martinez M, Bengrine Lefevre L, Priou F, Cloarec N, Venat L, Selle F, Berton D, Collard O, Coquan E, Le Saux O, Treilleux I, Gouerant S, Angelergues A, Joly F, and Tredan O
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- Humans, Female, Middle Aged, Aged, Paclitaxel therapeutic use, Paclitaxel administration & dosage, Paclitaxel adverse effects, Chemotherapy, Adjuvant methods, Adult, Ovarian Neoplasms drug therapy, Ovarian Neoplasms pathology, Ovarian Neoplasms surgery, Ovarian Neoplasms mortality, Cystadenocarcinoma, Serous drug therapy, Cystadenocarcinoma, Serous pathology, Cystadenocarcinoma, Serous surgery, Cystadenocarcinoma, Serous mortality, Progression-Free Survival, Cytoreduction Surgical Procedures, Neoplasm Staging, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized administration & dosage, Neoadjuvant Therapy methods, Carboplatin therapeutic use, Carboplatin administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use
- Abstract
This open-label, non-comparative, 2:1 randomized, phase II trial (NCT03275506) in women with stage IIIC/IV high-grade serous carcinoma (HGSC) for whom upfront complete resection was unachievable assessed whether adding pembrolizumab (200 mg every 3 weeks) to standard-of-care carboplatin plus paclitaxel yielded a complete resection rate (CRR) of at least 50%. Postoperatively patients continued assigned treatment for a maximum of 2 years. Postoperative bevacizumab was optional. The primary endpoint was independently assessed CRR at interval debulking surgery. Secondary endpoints were Completeness of Cytoreduction Index (CCI) and peritoneal cancer index (PCI) scores, objective and best response rates, progression-free survival, overall survival, safety, postoperative morbidity, and pathological complete response. The CRR in 61 pembrolizumab-treated patients was 74% (one-sided 95% CI = 63%), exceeding the prespecified ≥50% threshold and meeting the primary objective. The CRR without pembrolizumab was 70% (one-sided 95% CI = 54%). In the remaining patients CCI scores were ≥3 in 27% of the standard-of-care group and 18% of the investigational group and CC1 in 3% of the investigational group. PCI score decreased by a mean of 9.6 in the standard-of-care group and 10.2 in the investigational group. Objective response rates were 60% and 72%, respectively, and best overall response rates were 83% and 90%, respectively. Progression-free survival was similar with the two regimens (median 20.8 versus 19.4 months in the standard-of-care versus investigational arms, respectively) but overall survival favored pembrolizumab-containing therapy (median 35.3 versus 49.8 months, respectively). The most common grade ≥3 adverse events with pembrolizumab-containing therapy were anemia during neoadjuvant therapy and infection/fever postoperatively. Pembrolizumab was discontinued prematurely because of adverse events in 23% of pembrolizumab-treated patients. Combining pembrolizumab with neoadjuvant chemotherapy is feasible for HGSC considered not completely resectable; observed activity in some subgroups justifies further evaluation to improve understanding of the role of immunotherapy in HGSC., (© 2024. The Author(s).)
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- 2024
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28. The association of histopathologic features after neoadjuvant chemo-immunotherapy with clinical outcome: Sub-analyses from the randomized double-blinded, placebo-controlled, Phase III IMagyn050/GOG3015/ENGOT-ov39 study.
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Mhawech-Fauceglia P, McCarthy D, Tonooka A, Scambia G, Garcia Y, Dundr P, Mills AM, Moore K, Sanada S, Bradford L, Stella GC, Bookman M, Sharma SK, Selle F, Molinero L, He Y, Khor V, Landen C, and Lin YG
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- Humans, Female, Middle Aged, Double-Blind Method, Aged, Adult, Immunotherapy methods, Cytoreduction Surgical Procedures, Neoplasm, Residual, Progression-Free Survival, Neoadjuvant Therapy methods, Bevacizumab administration & dosage, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use
- Abstract
Objective: Histopathologic characteristics after neoadjuvant chemotherapy (NACT) may correlate with outcome. This study evaluates histopathologic features after immunotherapy and NACT/bevacizumab, and associated clinical outcomes., Methods: Evaluable tissue from IMagyn050/GOG3015/ENGOT-ov39 patients from prespecified anatomic sites from interval cytoreductive surgery (ICS) after NACT/bevacizumab plus atezolizumab/placebo underwent central histopathologic scoring and analyzed with clinical outcomes., Results: The predefined population had 243 evaluable NACT patients, with 48.1% tumors being PD-L1-positive. No statistically significant differences in PFS (16.9 months vs. 19.2 months, p = 0.21) or OS (41.5 months vs. 45.1 months, p = 0.67) between treatment arms were seen. Substantial residual tumor (RT) (3+) was identified in 26% atezolizumab vs. 24% placebo arms (p = 0.94). Most showed no (1+) necrosis (82% vs. 96%, respectively, p = 0.69), moderate (2+) to severe (3+) fibrosis (71% vs. 75%, respectively, p = 0.82), and extensive (2+) inflammation (53% vs. 47% respectively, p = 0.48). No significant histopathologic differences were identified by tissue site or by arm. Multivariate analyses showed increased risk for progression with moderate and substantial RT (13.6 mon vs. 21.1 mon, hazard ratio 2.0, p < 0.01; 13.6 mon vs. 21.1 mon, HR 1.9, p < 0.01, respectively); but decreased risk for death with extensive inflammation (46.9 mon vs. 36.3 mon, HR 0.65, p = 0.02). Inflammation also correlated with greater likelihood of response to NACT/bevacizumab plus immunotherapy (odds ratio 2.9, p < 0.01). Modeling showed inflammation as a consistent but modest predictor for OS., Conclusions: Detailed histologic assessment of ICS specimens appear to identify characteristics, such as inflammation and residual tumor, that may provide insight to certain clinical outcomes. Future work potentially leveraging emerging tools may provide further insight into outcomes., Competing Interests: Declaration of competing interest GS reports grant/research support from MSD Italia S.r.l.; consultancy for TESARO Bio Italy S.r.l. and Johnson & Johnson; and speaker bureau/honoraria from Clovis Oncology Italy S.r.l. YG reports fees from advisory boards from GlaxoSmithKline and AstraZeneca; and fees from travel grants and speaker's bureau from Roche, AstraZeneca, MSD, and GlaxoSmithKline. PD reports advisory board honoraria and speaking fees from Novartis, Janssen-Cilag, Amgen, Merck Sharp and Dohme, Roche, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, and Merck. KNM reports research funding from PTC Therapeutics, Lilly, Genentech/Roche, GlaxoSmithKline, Verastem, and Clovis; advisory Board/Consultant role with Aadi, AstraZeneca, Aravive, Alkemeres, Blueprint pharma, Clovis, Caris, Duality, Eisai, EMD Serono, Gilead, GSK, Genentech/Roche, Immunogen, IMab, Janssen, Merck, Mersana, Myriad, Novartis, OncXerna, OncoNova, Panavance, VBL Therapeutics, Verastem, Zentalis, and Tubulis; and Associate Director GOG Partners with GOG Foundation BOD (uncompensated) and ASCO BOD (uncompensated). GCS reports conflicts with AstraZeneca, GlaxoSmithKine, and Clovis. MB reports participation in ad-hoc advisory boards for Genentech-Roche, Merck Sharp & Dohme, AstraZeneca, Clovis Oncology, Seattle Genetics, Aravive, and AbbVie; and consulting fees paid to institution. FS reports honoraria from Astra Zeneca, MSD, Clovis Oncology, Sandoz, and GlaxoSmithKine-Tesaro; consulting or advisory role for AstraZeneca, MSD, and GlaxoSmithKine-Tesaro; speaker's bureau from AstraZeneca, MSD, and GlaxoSmithKline-Tesaro; and travel, accommodation, and/or expenses from AstraZeneca, MSD, GlaxoSmithKline-Tesaro, and Roche. LM reports employment by Genentech and is a stockholder in Roche. YH reports employment by Parexel to provide statistical service for Roche. VK reports employment by Genentech and is a stockholder in Roche. CL reports research funding (institution) from Roche. YGL reports employment by Genentech and is a stockholder in Roche. PM-F reports consulting fees for Genentech-Roche. DM, AT, AMM, SS, LB and SKS report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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29. Author Correction: Bevacizumab, olaparib, and durvalumab in patients with relapsed ovarian cancer: a phase II clinical trial from the GINECO group.
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Freyer G, Floquet A, Tredan O, Carrot A, Langlois-Jacques C, Lopez J, Selle F, Abdeddaim C, Leary A, Dubot-Poitelon C, Fabbro M, Gladieff L, and Lamuraglia M
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- 2024
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30. A phase II, multicenter, open-label study of abemaciclib and letrozole in patients with estrogen receptor-positive rare ovarian cancer: ALEPRO trial.
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Ottenbourgs T, van Gorp T, Kridelka F, Baert T, Denys H, Selle F, Baas I, Van Rompuy AS, Lambrechts D, and Van Nieuwenhuysen E
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- Adult, Female, Humans, Aminopyridines therapeutic use, Letrozole therapeutic use, Receptors, Estrogen genetics, Receptors, Estrogen metabolism, Benzimidazoles, Carcinoma, Ovarian Epithelial drug therapy, Carcinoma, Ovarian Epithelial genetics, Carcinoma, Ovarian Epithelial pathology, Ovarian Neoplasms pathology
- Abstract
Background: Low-grade serous and endometrioid ovarian cancers and adult-type granulosa cell tumors are rare ovarian malignancies that show high estrogen receptor positivity. Recurrences of these subtypes of ovarian cancer are often treated with conventional chemotherapy, although response rates are disappointing., Primary Objective: To determine the overall response rate of the combination therapy of abemaciclib and letrozole in patients with estrogen receptor-positive rare ovarian cancers., Study Hypothesis: The combination therapy of abemaciclib and letrozole will provide a clinically meaningful therapeutic benefit, with an overall response rate of >25%., Trial Design: This is a phase II, international, multicenter, open-label, single-arm study to evaluate the efficacy and safety of abemaciclib and letrozole in patients with advanced, recurrent, and/or metastatic estrogen receptor-positive, rare ovarian cancer. The study will follow a tandem two-stage design., Major Inclusion/exclusion Criteria: Patients must have histologically confirmed low-grade serous/endometrioid ovarian cancer or adult-type granulosa cell tumor with estrogen receptor positivity on immunohistochemistry. Patients need to have recurrent and measurable disease according to Radiologic Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A maximum of two prior lines of endocrine therapy are allowed, and patients cannot have previously received a cyclin-dependent kinase inhibitor. Patients with platinum-refractory disease are not allowed in any stage of the study., Primary Endpoint: Investigator-assessed confirmed overall response rate, defined as the proportion of patients with a complete or partial response according to RECIST v1.1., Sample Size: 40 to 100 patients will be included, depending on the results of the interim analysis. Patients will be included in Belgium, France and the Netherlands., Estimated Dates for Completing Accrual and Presenting Results: Patient recruitment will be completed by the end of 2025 and reporting of the final study results will be done by the end of 2027., Trial Registration Number: NCT05872204., Competing Interests: Competing interests: EVN reports consulting fees from Regeneron, Oncoinvent, AstraZeneca, Roche, Seagen, Novartis, Merck and Verastem; and receipt of study drug abemaciclib for this study from Eli Lilly. TVG reports grants/contracts from the Fund for Scientific Research-Flanders (FWO); consulting fees (paid to the institution) from AstraZeneca, Eisai, OncXerna Therapeutics, MSD, GSK, ImmunoGen, Seagen, Tubulis and Zentalis; honoraria (paid to the institution) from ImmunoGen, GSK, AstraZeneca; and meeting/travel support from Amgen, Pfizer, Roche, GSK, Novartis, ImmunoGen, MSD, PharmaMar and Sanofi-Aventis. FK reports grants/contracts from GSK, PharmaMar and AstraZeneca; consulting fees from GSK and PharmaMar; honoraria from GSK; expert testimony for GSK and AstraZeneca; meeting/travel support from PharmaMar and AstraZeneca; and advisory board for AstraZeneca. TB reports grants/contracts from Roche; honoraria from Novartis, AstraZeneca and Eli Lilly; and meeting/travel support from AstraZeneca, GSK and MSD. HD reports grants/contracts (paid to the institution) from Gilead; consulting fees (paid to the institution) from GSK and Gilead; honoraria (paid to the institution) from AstraZeneca, GSK, Eli Lilly, Gilead, Amgen, Roche, Leo Pharma, MSD, Daiichi Sannkyo and Teva Pharmaceuticals; meeting/travel support (paid to the institution) from GSK, AstraZeneca, Gilead, Roche, MSD, Pfizer, Teva Pharmaceuticals and PharmaMar; and advisory board (paid to the institution) for GSK, AstraZeneca, MSD, Menarini, Eli Lilly, Pfizer, Gilead, Seagen. FS reports consulting fees from AstraZeneca, GSK Tesaro and MSD; and honoraria from AstraZeneca, GSK Tesaro, MSD and Eisai. IB reports grants from Springer Healthcare and GSK; honoraria from Status Plus Gynaecongres; and participation on the DSMB of the Direct2 study (no payments).TO, ASVR and DL have no competing interests to disclose., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)
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- 2024
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31. Bevacizumab, olaparib, and durvalumab in patients with relapsed ovarian cancer: a phase II clinical trial from the GINECO group.
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Freyer G, Floquet A, Tredan O, Carrot A, Langlois-Jacques C, Lopez J, Selle F, Abdeddaim C, Leary A, Dubot-Poitelon C, Fabbro M, Gladieff L, and Lamuraglia M
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- Female, Humans, Antibodies, Monoclonal, Bevacizumab therapeutic use, Carcinoma, Ovarian Epithelial, Chronic Disease, Phthalazines, Piperazines, Platinum, Recurrence, Ovarian Neoplasms drug therapy, Antineoplastic Combined Chemotherapy Protocols adverse effects
- Abstract
Most patients with advanced ovarian cancer (AOC) ultimately relapse after platinum-based chemotherapy. Combining bevacizumab, olaparib, and durvalumab likely drives synergistic activity. This open-label phase 2 study (NCT04015739) aimed to assess activity and safety of this triple combination in female patients with relapsed high-grade AOC following prior platinum-based therapy. Patients were treated with olaparib (300 mg orally, twice daily), the bevacizumab biosimilar FKB238 (15 mg/kg intravenously, once-every-3-weeks), and durvalumab (1.12 g intravenously, once-every-3-weeks) in nine French centers. The primary endpoint was the non-progression rate at 3 months for platinum-resistant relapse or 6 months for platinum-sensitive relapse per RECIST 1.1 and irRECIST. Secondary endpoints were CA-125 decline with CA-125 ELIMination rate constant K (KELIM-B) per CA-125 longitudinal kinetics over 100 days, progression free survival and overall survival, tumor response, and safety. Non-progression rates were 69.8% (90%CI 55.9%-80.0%) at 3 months for platinum-resistant relapse patients (N = 41), meeting the prespecified endpoint, and 43.8% (90%CI 29.0%-57.4%) at 6 months for platinum-sensitive relapse (N = 33), not meeting the prespecified endpoint. Median progression-free survival was 4.1 months (95%CI 3.5-5.9) and 4.9 months (95%CI 2.9-7.0) respectively. Favorable KELIM-B was associated with better survival. No toxic deaths or major safety signals were observed. Here we show that further investigation of this triple combination may be considered in AOC patients with platinum-resistant relapse., (© 2024. The Author(s).)
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- 2024
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32. Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial.
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Kurtz JE, Pujade-Lauraine E, Oaknin A, Belin L, Leitner K, Cibula D, Denys H, Rosengarten O, Rodrigues M, de Gregorio N, Martinez García J, Petru E, Kocián R, Vergote I, Pautier P, Schmalfeldt B, Gaba L, Polterauer S, Mouret Reynier MA, Sehouli J, Churruca C, Selle F, Joly F, D'Hondt V, Bultot-Boissier É, Lebreton C, Lotz JP, Largillier R, Heudel PE, and Heitz F
- Subjects
- Female, Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bevacizumab, Carcinoma, Ovarian Epithelial drug therapy, Neoplasm Recurrence, Local drug therapy, Platinum therapeutic use, Quality of Life, B7-H1 Antigen therapeutic use, Ovarian Neoplasms drug therapy, Ovarian Neoplasms pathology
- Abstract
Purpose: Platinum-based doublets with concurrent and maintenance bevacizumab are standard therapy for ovarian cancer (OC) relapsing after a platinum-free interval (PFI) >6 months. Immunotherapy may be synergistic with bevacizumab and chemotherapy., Patients and Methods: ATALANTE/ENGOT-ov29 (ClinicalTrials.gov identifier: NCT02891824), a placebo-controlled double-blinded randomized phase III trial, enrolled patients with recurrent epithelial OC, one to two previous chemotherapy lines, and PFI >6 months. Eligible patients were randomly assigned 2:1 to atezolizumab (1,200 mg once every 3 weeks or equivalent) or placebo for up to 24 months, combined with bevacizumab and six cycles of chemotherapy doublet, stratified by PFI, PD-L1 status, and chemotherapy regimen. Coprimary end points were investigator-assessed progression-free survival (PFS) in the intention-to-treat (ITT) and PD-L1-positive populations (alpha .025 for each population)., Results: Between September 2016 and October 2019, 614 patients were randomly assigned: 410 to atezolizumab and 204 to placebo. Only 38% had PD-L1-positive tumors. After 3 years' median follow-up, the PFS difference between atezolizumab and placebo did not reach statistical significance in the ITT (hazard ratio [HR], 0.83; 95% CI, 0.69 to 0.99; P = .041; median 13.5 v 11.3 months, respectively) or PD-L1-positive (HR, 0.86; 95% CI, 0.63 to 1.16; P = .30; median 15.2 v 13.1 months, respectively) populations. The immature overall survival (OS) HR was 0.81 (95% CI, 0.65 to 1.01; median 35.5 v 30.6 months with atezolizumab v placebo, respectively). Global health-related quality of life did not differ between treatment arms. Grade ≥3 adverse events (AEs) occurred in 88% of atezolizumab-treated and 87% of placebo-treated patients; grade ≥3 AEs typical of immunotherapy were more common with atezolizumab (13% v 8%, respectively)., Conclusion: ATALANTE/ENGOT-ov29 did not meet its coprimary PFS objectives in the ITT or PD-L1-positive populations. OS follow-up continues. Further research on biopsy samples is warranted to decipher the immunologic landscape of late-relapsing OC.
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- 2023
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33. Impact of surgery and chemotherapy in ovarian sex cord-stromal tumors from the multicentric Salomé study including 469 patients. A TMRG and GINECO group study.
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Hanvic B, Lecuru F, Vanacker H, Pautier P, Narducci F, Cherifi F, Floquet A, Angeles MA, Berton D, Pomel C, Kalbacher E, Provansal M, Fernandez Y, Rouge TM, Roméo C, Laas E, Morice P, Hudry D, Meriaux E, Guyon F, Illac-Vauquelin C, Selle F, Meeus P, Genestie C, Salleron J, and Ray-Coquard I
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- Adult, Female, Humans, Aged, Retrospective Studies, Neoplasm Recurrence, Local pathology, Chemotherapy, Adjuvant, Neoplasm Staging, Ovarian Neoplasms drug therapy, Ovarian Neoplasms surgery, Sex Cord-Gonadal Stromal Tumors drug therapy, Sex Cord-Gonadal Stromal Tumors surgery, Granulosa Cell Tumor drug therapy, Granulosa Cell Tumor surgery
- Abstract
Objective: Identifying prognostic factors and evaluating the impact of adjuvant chemotherapy in patients with sex cord stromal tumors (SCST) is crucial. In this study, we aimed to address these challenges., Methods: We conducted a retrospective analysis of data from 13 centers of the French Rare malignant gynecological tumors (TMRG) network. We enrolled 469 adult patients with malignant SCST who received upfront surgery since 2011 to July 2015., Results: 75% were diagnosed with adult Granulosa cell tumors, and 23% had another subtype. With a median follow-up of 6.4 years, 154 patients (33%) developed a first recurrence, 82 (17%) two recurrences, and 49 (10%) three recurrences. Adjuvant chemotherapy was administered in 14.7% of patients at initial diagnosis. In relapse, perioperative chemotherapy was administered in 58.5%, 28.2%, and 23.8% of patients, respectively, in the first, second, and third relapse. In the first-line therapy, age under 70 years, FIGO stage, and complete surgery were associated with longer progression-free survival (PFS). Chemotherapy had no impact on PFS in early-stage disease (FIGO I-II). The PFS was similar using BEP or other chemotherapy regimens (HR 0.88 [0.43; 1.81]) in the first-line therapy. In case of recurrence, PFS was statistically prolonged by complete surgery, but perioperative chemotherapy use did not impact PFS., Conclusion: Chemotherapy use did not impact survival in the first-line or relapse setting in SCST. Only surgery and its quality demonstrated benefit for PFS in ovarian SCST in any lines of treatment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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34. Prise en charge des carcinomes ovariens de haut grade séreux et/ou endométrioïdes de stades avancés (III-IV) et testing HRD-BRCA en 2023 : actualisation selon les données publiées et/ou présentées en 2022.
- Author
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Selle F, Joly F, Gladieff L, Prulhière K, Leary A, Kalbacher E, Rouleau E, and Ray-Coquard I
- Subjects
- Female, Humans, Carcinoma, Ovarian Epithelial drug therapy, BRCA2 Protein genetics, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use, Genomic Instability, Ovarian Neoplasms drug therapy, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology
- Abstract
Management of high grade, serous and/or endometrioid, advanced (stages III-IV) ovarian carcinomas and HRD-BRCA testing in 2023: update according to data published/presented in 2022 Molecular analysis of ovarian carcinomas must be now systematically performed to determine BRCA1 and BRCA2 status as well as genomic instability score. Several types of tests are available. From a clinical perspective, new data from phase III clinical trials presented in 2022 confirm the key role of PARP inhibitors in first-line medical treatment of high-grade serous ovarian cancers. A new algorithm that includes all new evidence is proposed for selection of first-line therapy., (Copyright © 2023 Elsevier Masson SAS. Tous droits réservés. All rights reserved.)
- Published
- 2023
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35. Evaluation of Scores to Reflect Toxicity Impact on Quality of Life of Patients With Platinum-Resistant Ovarian Cancer: AURELIA Substudy.
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Lequesne J, Joly F, Peron J, Ray-Coquard I, Hardy-Bessard AC, Selle F, Berton D, Follana P, Fabbro M, Lortholary A, Pujade-Lauraine E, Lefèvre-Arbogast S, and Coquan E
- Subjects
- Female, Humans, Bevacizumab adverse effects, Carcinoma, Ovarian Epithelial, Ovarian Neoplasms drug therapy, Quality of Life
- Abstract
Background: Current standards for toxicity reporting do not fully capture the impact of adverse events (AEs) on patients' quality of life (QoL). This study aimed to evaluate the association between toxicity and QoL by using toxicity scores that take into account CTCAE grade grouping and AE duration and cumulation., Methods: Analyses were performed on the AURELIA trial dataset, including 361 patients with platinum-resistant ovarian cancer treated with chemotherapy alone or with bevacizumab. Global and physical functioning QoL were issued from the EORTC QoL Questionnaire-Core 30 (QLQ-C30), collected at baseline and 8/9 and 16/18 weeks after treatment initiation. Four toxicity scores were computed: the total number of AEs, multiplied by their grade and not, and the cumulative duration of AEs, weighted by their grade and not. Each score included all AEs or only grade 3/4 nonlaboratory or treatment-related AEs. The relationship between toxicity scores and QoL was assessed through linear mixed regression., Results: We found that 171 (47.5%) and 43 (11.9%) patients experienced at least one grade 3 or 4 AE, respectively, whereas 113 (31.4%) experienced grade 2 AEs only. Physical QoL was negatively associated with all toxicity scores when computed with all grades of AEs (all P<.01), with a weaker association when treatment-related AEs were considered. Global QoL was negatively associated with toxicity scores computed with nonlaboratory all-grade AEs only (β, -3.42 to -3.13; all P<.01). Degrees of association were lower when considering the AE duration., Conclusions: In this analysis of patients with platinum-resistant ovarian cancer, toxicity scores based on the cumulative number of AEs, modulated or not by grade, were more effective at predicting QoL changes than those based on AE duration. Toxicity impact on QoL was better reflected when grade 2 AEs were taken into account together with grade 3/4 AEs, whatever their treatment imputability, and when laboratory AEs were excluded.
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- 2023
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36. Optimal Treatment Duration of Bevacizumab as Front-Line Therapy for Advanced Ovarian Cancer: AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 Open-Label Randomized Phase III Trial.
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Pfisterer J, Joly F, Kristensen G, Rau J, Mahner S, Pautier P, El-Balat A, Kurtz JE, Canzler U, Sehouli J, Heubner ML, Hartkopf AD, Baumann K, Hasenburg A, Hanker LC, Belau A, Schmalfeldt B, Denschlag D, Park-Simon TW, Selle F, Jackisch C, Burges A, Lück HJ, Emons G, Meier W, Gropp-Meier M, Schröder W, de Gregorio N, Hilpert F, and Harter P
- Subjects
- Humans, Female, Bevacizumab, Duration of Therapy, Carcinoma, Ovarian Epithelial drug therapy, Carcinoma, Ovarian Epithelial pathology, Carboplatin, Paclitaxel, Antineoplastic Combined Chemotherapy Protocols adverse effects, Ovarian Neoplasms pathology, Peritoneal Neoplasms drug therapy, Peritoneal Neoplasms pathology
- Abstract
Purpose: To compare standard versus extended duration of bevacizumab treatment in combination with front-line chemotherapy in women with newly diagnosed stage IIB-IV ovarian cancer., Methods: In this multicenter, open-label, randomized phase III trial (ClinicalTrials.gov identifier: NCT01462890), patients with newly diagnosed International Federation of Gynecology and Obstetrics stage IIB-IV epithelial ovarian, fallopian tube, or peritoneal cancer underwent primary cytoreductive surgery followed by six cycles of chemotherapy (paclitaxel 175 mg/m
2 plus carboplatin area under the curve 5 once every 3 weeks) and bevacizumab (15 mg/kg once every 3 weeks). Patients were randomly assigned 1:1 to receive bevacizumab for either 15 or 30 months, stratified by International Federation of Gynecology and Obstetrics stage/residual tumor. The primary end point was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary end points included overall survival (OS), safety, and tolerability., Results: Between November 11, 2011, and August 6, 2013, 927 women were randomly assigned. There was no difference in PFS between treatment arms (hazard ratio, 0.99; 95% CI, 0.85 to 1.15; unstratified log-rank P = .90). Median PFS was 24.2 versus 26.0 months with standard versus extended duration of bevacizumab, respectively; restricted mean PFS was 39.5 versus 39.3 months, respectively. There was no OS difference between treatment arms (hazard ratio, 1.04; 95% CI, 0.87 to 1.23; P = .68). Serious/nonserious adverse events of special interest occurred in 29% versus 34% of patients in the standard versus experimental arms, respectively, and were consistent with the known safety profile of standard bevacizumab., Conclusion: Longer treatment duration with bevacizumab for up to 30 months did not improve PFS or OS in patients with primary epithelial ovarian, fallopian tube, or peritoneal cancer. A bevacizumab treatment duration of 15 months remains the standard of care.- Published
- 2023
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37. Abasic RNA: its formation and potential role in cellular stress response.
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Prashar T, De La Selle F, and Hudak KA
- Subjects
- RNA, Messenger genetics, RNA, Messenger metabolism, DNA Repair, DNA chemistry, RNA, Ribosomal, RNA, Transfer genetics, RNA chemistry, DNA Damage
- Abstract
RNA is integral to gene expression as messenger RNA (mRNA), transfer RNA (tRNA) and ribosomal RNA (rRNA) each play roles to transmit information from DNA into synthesis of functional proteins. During their lifespan, these nucleic acids may be chemically modified by alkylation, oxidation and the removal of bases, which alters their activity. Though much research has been devoted to the detection and repair of damaged DNA, RNA is viewed as a short-lived molecule that is quickly degraded upon damage. However, recent studies indicate that RNAs that become modified, particularly during stress, function as important signalling molecules. In this review, we focus on the effects of abasic RNAs and the modifications that lead to the loss of a base, as RNAs that are initially methylated or oxidized often become abasic. We describe how these chemical changes occur and cite recent work showing that in addition to being indicators of damage, abasic RNAs function as signals that mediate downstream cellular responses to stress.
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- 2023
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38. [Practical management of PARP inhibitors: A French DELPHI consensus].
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Selle F, Boffa JJ, Etienne G, Angelergues A, Augereau P, Berton D, Dielenseger P, Fabbro M, Falandry C, Follana P, Gladieff L, Joly F, Kurtz JE, Matta C, Mouret-Reynier MA, Schmitt A, Scotté F, Marjollet C, and Floquet A
- Subjects
- Humans, Consensus, Delphi Technique, Health Personnel, Poly(ADP-ribose) Polymerase Inhibitors adverse effects, Quality of Life
- Abstract
Objective: Despite an increasing number of therapeutic indications, there are no specific recommendations regarding the management of PARP inhibitors other than what is specified in the SmPC of each substance. A Delphi French consensus was conducted to establish practical guidelines to meet the needs identified by healthcare professionals and patients., Method: Following the Delphi method, statements to optimize PARP inhibitor management were drafted by a multidisciplinary Steering Committee made up of 17 experts. These statements were submitted to the independent and anonymous vote of clinicians involved in treating patients on PARP inhibitors., Results: This article presents 52 statements on the following topics: initiation and treatment; management of adverse events (hematological effects, gastrointestinal effects, renal effects, pulmonary effects, cutaneous effects, hypertension, insomnia, fatigue, dizziness); special populations and situations; communication with the patient; adherence. Forty-nine statements obtained voter consensus after 3 voting rounds. A hematologist and a nephrologist supplemented this task by drafting an expert opinion on the risk of occurrence of secondary leukemia and nephrological toxicity., Conclusions: This paper is the first Delphi consensus on the practical management of PARP inhibitors. The pragmatic recommendations resulting from this paper should make it possible to manage the side effects of PARP inhibitors better and thus prevent early treatment discontinuation and improve patient adherence by preserving quality of life., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2022
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39. Efficacy of niraparib by time of surgery and postoperative residual disease status: A post hoc analysis of patients in the PRIMA/ENGOT-OV26/GOG-3012 study.
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O'Cearbhaill RE, Pérez-Fidalgo JA, Monk BJ, Tusquets I, McCormick C, Fuentes J, Moore RG, Vulsteke C, Shahin MS, Forget F, Bradley WH, Hietanen S, O'Malley DM, Dørum A, Slomovitz BM, Baumann K, Selle F, Calvert PM, Artioli G, Levy T, Kumar A, Malinowska IA, Li Y, Gupta D, and González-Martín A
- Subjects
- Carcinoma, Ovarian Epithelial drug therapy, Carcinoma, Ovarian Epithelial surgery, Chemotherapy, Adjuvant, Cytoreduction Surgical Procedures, Female, Humans, Indazoles therapeutic use, Neoadjuvant Therapy, Neoplasm Staging, Neoplasm, Residual, Piperidines, Ovarian Neoplasms drug therapy, Ovarian Neoplasms pathology, Ovarian Neoplasms surgery
- Abstract
Objective: To evaluate the association between surgical timing and postoperative residual disease status on the efficacy of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer at high risk of recurrence., Methods: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study of niraparib in patients with newly diagnosed primary advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete/partial response to first-line platinum-based chemotherapy. Progression-free survival (PFS) was assessed by surgical status (primary debulking surgery [PDS] vs neoadjuvant chemotherapy/interval debulking surgery [NACT/IDS]) and postoperative residual disease status (no visible residual disease [NVRD] vs visible residual disease [VRD]) in the intent-to-treat population., Results: In PRIMA (N = 733), 236 (32.2%) patients underwent PDS, and 481 (65.6%) received NACT/IDS before enrollment. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) for progression were similar in PDS (13.7 vs 8.2 months; HR, 0.67 [0.47-0.96]) and NACT/IDS (14.2 vs 8.2 months; HR, 0.57 [0.44-0.73]) subgroups. In patients who received NACT/IDS and had NVRD (n = 304), the hazard ratio (95% CI) for progression was 0.65 (0.46-0.91). In patients with VRD following PDS (n = 183) or NACT/IDS (n = 149), the hazard ratios (95% CI) for progression were 0.58 (0.39-0.86) and 0.41 (0.27-0.62), respectively. PFS was not evaluable for patients with PDS and NVRD because of sample size (n = 37)., Conclusions: In this post hoc analysis, niraparib efficacy was similar across PDS and NACT/IDS subgroups. Patients who had NACT/IDS and VRD had the highest reduction in the risk of progression with niraparib maintenance., Competing Interests: Declaration of Competing Interest REO reports participating in advisory boards with Bayer, Fresenius Kabi, GlaxoSmithKline, Immunogen, Regeneron, and Seattle Genetics; personal fees from GOG Foundation; and service as a noncompensated steering committee member for the PRIMA (niraparib) and DUO-O (olaparib) studies; institutional research support grants from AstraZeneca/Merck, Atara Biotherapeutics/Bayer, Genentech, Genmab, GlaxoSmithKline, Gynecologic Oncology Group Foundation, Juno Therapeutics, Kite/Gilead, Ludwig Institute for Cancer Research, Regeneron, Sellas Life Sciences, Stem CentRx, Syndax, TapImmune Inc., and TCR2 Therapeutics. JAPF reports personal fees from Abilify Pharma, Amgen, AstraZeneca, Clinigen, Clovis, GlaxoSmithKline, and Roche; and institutional grants from GlaxoSmithKline. BJM reports consulting fees from Agenus, Akeso Bio, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, Macrogenics, Mersana, Myriad, Novartis, Novocure, Regeneron, Sorrento, Pfizer, Puma, US Oncology Research, and VBL; speaker's bureau honoraria from AstraZeneca, Clovis, Eisai, Merck, Roche/Genentech, TESARO/GSK; and is an investigator for US Oncology Research. IT reports personal fees from Celgene and Roche Pharma AG; institutional grants from Roche; and travel support from Roche. RGM reports personal fees from Abcodia Inc., Fujirebio Diagnostics Inc., and Humphries Pharmaceutical; and institutional grants from Angle Plc. MSS reports personal fees from AstraZeneca, Clovis Oncology, GlaxoSmithKline, Merck, and Pacira Pharmaceuticals Inc.; and institutional grants from GlaxoSmithKline. DO reports personal fees from Agenus, Eisai, GlaxoSmithKline, and Immunogen; consultant/advisory board for Abbvie, Ambry, Amgen, Array Biopharma, Clovis, EMD Serono, Ergomed, Janssen/J&J, INC Research Inc., inVentiv Health Clinical, Iovance Biotherapeutics Inc., Myriad Genetics, Novacure, Regeneron, Tarveda, and VentiRx; steering committee for Genentech/Roche and Merck; institutional funding from Ajinomoto Inc., Bristol Myers Squibb, Cerulean Pharma, GOG Foundation, Ludwig Cancer Research, New Mexico Cancer Care Alliance, PRA International, Stemcentrx Inc., Serono Inc., Tracon Pharmaceuticals, and Yale University. BMS reports consulting/advisory fees from Abbvie, AstraZeneca, Clovis, Eisai, Genentech, GlaxoSmithKline, GOG Foundation, Merck, and Myriad. FS reports personal fees from AstraZeneca, Clovis, GlaxoSmithKline, MSD, PharmaMar, and Roche; and travel support from AstraZeneca, GlaxoSmithKline, MSD, PharmaMar, and Roche. AK reports personal fees from AstraZeneca and GlaxoSmithKline. AGM reports consulting or advisory roles at Amgen, AstraZeneca, Clovis, Genmab, GlaxoSmithKline, Merck & Co., Mersana, Immunogen, Roche, Sotio, and Takeda; speaker's bureau compensation from AstraZeneca, Clovis, GlaxoSmithKline, Merck & Co., and Roche; institutional research funding from Roche and GlaxoSmithKline; and travel support from AstraZeneca, GlaxoSmithKline, and Roche. CM, CV, JF, FF, WHB, SH, AD, KB, PMC, GA, and TL have nothing to disclose. IAM and DG are employees of GlaxoSmithKline. YL was an employee at GlaxoSmithKline at the time of the analysis; currently an employee of Adagio Therapeutics Inc., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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40. Low probability of disease cure in advanced ovarian carcinomas before the PARP inhibitor era.
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You B, Van Wagensveld L, Tod M, Sonke GS, Horlings HM, Kruitwagen RFPM, Du Bois A, Selle F, Perren T, Pfisterer J, Joly F, Cook A, Kaminsky MC, Wollschlaeger K, Lortholary A, Tome O, Leary A, Freyer G, Van Der Aa M, and Colomban O
- Subjects
- Carcinoma, Ovarian Epithelial pathology, Chemotherapy, Adjuvant, Clinical Trials, Phase III as Topic, Cytoreduction Surgical Procedures methods, Female, Humans, Neoadjuvant Therapy methods, Neoplasm Staging, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use, Probability, Retrospective Studies, Antineoplastic Agents therapeutic use, Ovarian Neoplasms pathology
- Abstract
Background: In ovarian carcinomas, the likelihood of disease cure following first-line medical-surgical treatment has been poorly addressed. The objective was to: (a) assess the likelihood of long-term disease-free (LDF) > 5 years; and (b) evaluate the impact of the tumour primary chemosensitivity (assessed with the modelled CA-125 KELIM) with respect to disease stage, and completeness of debulking surgery., Methods: Three Phase III trial datasets (AGO-OVAR 9; AGO-OVAR 7; ICON-7) were retrospectively investigated in an "adjuvant dataset", whilst the Netherlands Cancer Registry was used in a "neoadjuvant dataset". The prognostic values of KELIM, disease stage and surgery outcomes regarding the likelihood of LDF were assessed using univariate/multivariate analyses., Results: Of 2029 patients in the "adjuvant dataset", 82 (4.0%) experienced LDF (Stage I-II: 25.9%; III: 2.1%; IV: 0.5%). Multivariate analyses identified disease stage and KELIM (OR = 4.24) as independent prognostic factors. Among the 1452 patients from the "neoadjuvant dataset", 36 (2.4%) had LDF (Stage II-III: 3.3%; IV: 1.3%). Using multivariate tests, high-risk diseases (OR = 0.18) and KELIM (OR = 2.96) were significant., Conclusion: The probability of LDF > 5 years after first-line treatment in 3486 patients (<4%) was lower than thought. These data could represent a reference for future studies meant to assess progress related to PARP inhibitors., (© 2022. The Author(s).)
- Published
- 2022
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41. Prise en charge chirurgicale du cancer épithélial de l'ovaire - première ligne et première rechute: Surgical management of epithelial ovarian cancer - first line and first relapse.
- Author
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Classe JM, Joly F, Lécuru F, Morice P, Pomel C, Selle F, and You B
- Subjects
- Carcinoma, Ovarian Epithelial pathology, Cytoreduction Surgical Procedures, Female, Humans, Laparotomy, Lymph Node Excision, Neoadjuvant Therapy, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Ovarian Neoplasms pathology, Carcinoma, Ovarian Epithelial surgery, Neoplasm Recurrence, Local surgery, Ovarian Neoplasms surgery
- Abstract
Based on recently published data, these recommendations present some evolutions in the surgical management of high grade epithelial ovarian cancers. In apparently early stages (FIGO I and II), surgical staging must be undertaken to confirm the absence of both peritoneal lesions and lymph node involvement (that might change stage and management). Neoadjuvant chemotherapy is not indicated, surgical exploration should be performed upfront, by laparotomy, to reduce the risk of rupture of the primary tumor. In advanced stages, the first step is to evaluate the feasibility of primary surgery with complete tumor cytoreduction. If it appears unfeasible, 3 or 4 cycles of neoadjuvant chemotherapy are administered before interval surgey. Whether it is implemented in the primary or interval setting, surgery must be performed by experimented teams, in an approved facility, having developed a rehabilitation program. Lymph node dissection is not mandatory if no adenopathies have been identified by imaging and by peroperative palpation. At first relapse, the surgical decision must be made by a multidisciplinary team, using scores predictive of complete cytoreduction (AGO or iMODEL criteria). Similarly as in first line, the objective is to achieve resection without any residual disease. Surveillance after first-line treatment must be adapted, according to the probability of another complete cytoreduction in case of late relapse, especially in patients who benefited from primary complete surgery and maintained good performance status., (Copyright © 2021 Société FranÇaise du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.)
- Published
- 2021
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42. Traitement médical de première ligne du cancer épithélial de l'ovaire de haut grade: First-line medical treatment of high-grade epithelial ovarian cancer.
- Author
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Selle F, Alexandre J, Prulhière K, Kalbacher E, Ray-Coquard I, and Leary A
- Subjects
- Algorithms, Bevacizumab therapeutic use, Carboplatin therapeutic use, Carcinoma, Ovarian Epithelial genetics, Carcinoma, Ovarian Epithelial pathology, Chemotherapy, Adjuvant, Drug Administration Schedule, Female, Genes, BRCA1, Genes, BRCA2, Humans, Indazoles therapeutic use, Maintenance Chemotherapy, Neoadjuvant Therapy, Neoplasm Grading, Neoplasm Staging, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology, Paclitaxel therapeutic use, Phthalazines therapeutic use, Piperazines therapeutic use, Piperidines therapeutic use, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Ovarian Epithelial drug therapy, Ovarian Neoplasms drug therapy
- Abstract
In early stages, standard treatment is adjuvant chemotherapy, consisting of platinum-based combination for 6 cycles, especially in serous and endometrioid high grade carcinomas. In advanced stages, indication of neoadjuvant chemotherapy must be discussed on a case-by-case basis in multidisciplinary meetings (MDM). Bevacizumab can also be considered in the neoadjuvant setting in some circumstances, always after discussion in MDM. Carboplatin plus paclitaxel every 21 days, with or without bevacizumab remains the standard of care for first-line chemotherapy. Inhibitors of poly-(ADP-riboses) polymerases (PARPi) have been approved and are reimbursed as maintenance monotherapy in tumors carrying BRCA1 or BRCA2 mutation after complete or partial response to chemotherapy. Two recent studies demonstrated the efficacy of PARPi on progression free survival, one for niraparib single-agent in patients with high-grade ovarian carcinoma regardless of BRCA status, the other one for the combination of bevacizumab and olaparib in patients with high grade carcinoma, with positive test for homologous recombination DNA repair deficiency (regardless of BRCA status). These two new modalities of maintenance therapy are now available in compassionate use programs or post compassionate use programs. Depending on pending decisions upon reimbursement, these indications might be somewhat modified., (Copyright © 2021 Société FranÇaise du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.)
- Published
- 2021
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43. Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer.
- Author
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O'Malley DM, Oaknin A, Monk BJ, Selle F, Rojas C, Gladieff L, Berton D, Leary A, Moore KN, Estevez-Diz MDP, Hardy-Bessard AC, Alexandre J, Opperman CP, de Azevedo CRAS, Randall LM, Feliu WO, Ancukiewicz M, and Ray-Coquard I
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized adverse effects, Diarrhea chemically induced, Diarrhea epidemiology, Diarrhea immunology, Drug Administration Schedule, Enterocolitis chemically induced, Enterocolitis epidemiology, Enterocolitis immunology, Female, Humans, Immune Checkpoint Inhibitors adverse effects, Infusions, Intravenous, Middle Aged, Neoplasm Recurrence, Local immunology, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local pathology, Progression-Free Survival, Response Evaluation Criteria in Solid Tumors, Uterine Cervical Neoplasms immunology, Uterine Cervical Neoplasms mortality, Uterine Cervical Neoplasms pathology, Antibodies, Monoclonal, Humanized administration & dosage, Immune Checkpoint Inhibitors administration & dosage, Neoplasm Recurrence, Local drug therapy, Programmed Cell Death 1 Receptor antagonists & inhibitors, Uterine Cervical Neoplasms drug therapy
- Abstract
Objective: This phase II clinical trial evaluated the safety and antitumor activity of balstilimab, an anti-PD-1 antibody, in patients with previously-treated, recurrent/metastatic cervical cancer., Methods: Eligible patients were 18 years or older with recurrent and/or metastatic cervical cancer and who had relapsed after a prior platinum-based treatment regimen for advanced disease. Balstilimab was administered intravenously at 3 mg/kg once every two weeks, for up to 24 months. The primary endpoint was objective response rate (ORR, RECIST v1.1) as assessed by an independent review committee., Results: At data cutoff, 161 women (median age, 53 years [range 25-81]) were enrolled and treated with balstilimab. Of these, 140 had measurable disease at baseline and one prior line of platinum-based therapy in the metastatic, persistent, or recurrent setting; these patients were included in the efficacy analyses. The ORR was 15% (95% CI, 10.0%-21.8%) and included 5 patients with a complete response and 16 with a partial response. The median duration of response was 15.4 months. In patients with PD-L1-positive tumors the ORR was 20%, however patients with PD-L1-negative tumors also responded to balstilimab (ORR, 7.9%). Responses were not restricted to tumors of squamous cell histology, and an ORR of 12.5% was seen in the subset of patients with cervical adenocarcinoma. The disease control rate was 49.3% (95% CI, 41.1%-57.5%). Immune-mediated enterocolitis (3.1%) and diarrhea (1.9%) were the most common grade 3 or higher treatment-related adverse events., Conclusion: Balstilimab demonstrated meaningful and durable clinical activity, with manageable safety, in patients with previously-treated, recurrent/metastatic cervical cancer., Competing Interests: Declaration of Competing Interest DMO reports personal fees and institutional grants from AstraZeneca, GSK/Tesaro, ImmunoGen, Janssen/Johnson & Johnson, Abbvie, Regeneron, Amgen, Clovis Oncology, Novocure, Genentech/Roche, Iovance, Eisai, Agenus, Merck, SeaGen, Novartis, Mersana; personal fees from Ambry, GOG Foundation, Myriad Genetics, Tarveda, Rubis, and Elevar; additional institutional funding from VentiRx Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research Stemcentrx, Inc., CERULEAN Pharma, Bristol-Myers Squibb, Serono, TRACON Pharmaceuticals, INC Research, Inc., inVentiv Health Clinical, PRA Intl and GenMab. AO reports personal fees from AstraZeneca, PharmaMar, Roche, Clinical Care Options, Clovis Oncology, Deciphera Pharmaceuticals, ImmunoGen, GenMab, Mersana, prIME Oncology, GlaxoSmithKline, and Tesaro; funding from AstraZeneca, Daiichi Sankyo, Eli Lilly and Company, Genentech, Immunomedics, Macrogenics, Merck Sharp & Dohme, Novartis, Pfizer, Piqur Therapeutics, Roche, Synthon, and Zenith Pharmaceuticals. BJM reports personal fees from Agenus, Akeso Bio, AstraZeneca, Genmab/Seattle Genetics, Iovance, Merck, Puma, Roche/Genentech, GOG Foundation, and GSK/Tesaro. FS reports personal fees and travel support from AstraZeneca, GSK/Tesaro, Merck Sharp & Dohme, Sandoz (Novartis), and Clovis Oncology, and Roche. CR reports personal fees from Merck, BMS, Roche, AstraZeneca, and Pfizer. LG reports personal fees from AstraZeneca, Clovis Oncology, GlaxoSmithKline, Merck Sharp & Dohme, and Roche; travel support from AstraZeneca and PharmaMar. AL reports personal fees from AstraZeneca, Tesaro, Clovis Oncology, Merck Sharp & Dohme, BIOCAD, AbilityPharma, Seattle Genetics, and Zentalis; institutional fees, grant and travel support from GlaxoSmithKline and Merck Serono. KNM reports personal fees from Aravive, AstraZeneca, Bristol Myers Squibb, Eisai, Elevar, GSK/Tesaro, Genentech/Roche, ImmunoGen, Merck, Mersana, Myriad, OncXerna, Sorrento, and VBL Therapeutics; funding from PTC Therapeutics, Lilly, and Merck. ACHB reports personal fees from AstraZeneca, Clovis Oncology, GlaxoSmithKline, Novartis, Pfizer, Roche, and Seagen. JA reports personal fees from AstraZeneca, GlaxoSmithKline, Roche, Merck Sharp & Dohme, PharmaMar; funding from Janssen and Merck Sharp & Dohme; travel support from Janssen, GlaxoSmithKline, and Novartis. CPO reports personal fees from Abbvie, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Genmab, GlaxoSmithKline, Tesaro, Mersana, PharmaMar; funding from Lilly, Roche, and Sanofi. CRdA reports personal fees from Merck Sharp & Dohme. LMR reports personal fees from AstraZeneca, Clovis Oncology, Eisai, EMD Serono, Genentech/Roche, GlaxoSmithKline, GOG Foundation, Mersana Therapeutics, Merck, Myriad Genetics, OnTarget, Rubius, BluPrint Oncology, Products in Knowledge; grant funding from Akeso Bio, Genentech, and Merck; travel support from GlaxoSmithKline. WOF reports employment by, and stock ownership in, Agenus Inc. MA reports employment by Agenus Inc. IRC reports personal fees from Abbvie, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Genmab, GlaxoSmithKline, Tesaro, Mersana, PharmaMar, and Roche; research funding from Bristol Myers Squibb, GlaxoSmithKline, and Merck Sharp & Dohme. All remaining authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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44. "Chronic fatigue, quality of life and long-term side-effects of chemotherapy in patients treated for non-epithelial ovarian cancer: national case-control protocol study of the GINECO-Vivrovaire rare tumors INCa French network for rare malignant ovarian tumors".
- Author
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Gernier F, Ahmed-Lecheheb D, Pautier P, Floquet A, Nadeau C, Frank S, Alexandre J, Selle F, Berton-Rigaud D, Kalbacher E, Orfeuvre H, Lortholary A, Augereau P, Labombarda F, Perrier L, Grellard JM, Licaj I, Clarisse B, Savoye AM, Bourien H, De La Motte Rouge T, Kurtz JE, Kerdja K, Lelaidier A, Charreton A, Ray-Coquard I, and Joly F
- Subjects
- Case-Control Studies, Fatigue Syndrome, Chronic pathology, Female, France, Humans, Male, Middle Aged, Ovarian Neoplasms mortality, Surveys and Questionnaires, Survival Rate, Fatigue Syndrome, Chronic etiology, Ovarian Neoplasms drug therapy, Quality of Life psychology
- Abstract
Background: Germ cell tumors and sex cord stromal tumors are rare cancers of the ovary. They mainly affect young women and are associated with a high survival rate. The standard treatment mainly involves conservative surgery combined with chemotherapy [bleomycin, etoposide and cisplatin (BEP)] depending on the stage and the prognostic factors, as for testicular cancers. As reported in testicular cancer survivors, chemotherapy may induce sequelae impacting quality of life, which has not yet been evaluated in survivors of germ cell tumors and sex cord stromal tumors. The GINECO-VIVROVAIRE-Rare tumor study is a two-step investigation aiming to assess i) chronic fatigue and quality of life and ii) long-term side-effects of chemotherapy with a focus on cardiovascular and pulmonary disorders., Methods: Using self-reported questionnaires, chronic fatigue and quality of life are compared between 134 ovarian cancer survivors (cancer-free ≥2 years after treatment) treated with surgery and chemotherapy and 2 control groups (67 ovarian cancer survivors treated with surgery alone and 67 age-matched healthy women). Medical data are collected from patient records. In the second step evaluating the long-term side-effects of chemotherapy, a subgroup of 90 patients treated with chemotherapy and 45 controls undergo the following work-up: cardiovascular evaluation (clinical examination, non-invasive cardiovascular tests to explore heart disease, blood tests), pulmonary function testing, audiogram, metabolic and hormonal blood tests. Costs of sequelae will be also assessed. Patients are selected from the registry of the INCa French Network for Rare Malignant Ovarian Tumors, and healthy women by the 'Seintinelles' connected network (collaborative research platform)., Discussion: This study will provide important data on the potential long-term physical side-effects of chemotherapy in survivors of Germ Cell Tumors (GCT) and Sex Cord Stromal Tumors (SCST), especially cardiovascular and pulmonary disorders, and neurotoxicity. The identification of long-term side-effects can contribute to adjusting the treatment of ovarian GCT or SCST patients and to managing follow-up with adapted recommendations regarding practices and chemotherapy regimens, in order to reduce toxicity while maintaining efficacy. Based on the results, intervention strategies could be proposed to improve the management of these patients during their treatment and in the long term., Trial Registration: This trial was registered at clinicaltrials.gov : 03418844 , on 1 February 2018. This trial was registered on 25 October 2017 under the unique European identification number (ID-RCB): 2017-A03028-45. Recruitment Status: Recruiting., Protocol Version: Version n° 4.2 dated from Feb 19, 2021., Trial Sponsor: Centre François Baclesse, 3 avenue du Général Harris, F-14076 Caen cedex 05, France., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
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