Randomized Controlled Trial Testing the Efficacy of Platinum-Free Interval Prolongation in Advanced Ovarian Cancer

The MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG Study

Sandro Pignata, Giovanni Scambia, Alessandra Bologna, Simona Signoriello, Ignace B Vergote, Uwe Wagner, Domenica Lorusso, Viviana Murgia, Roberto Sorio, Gabriella Ferrandina, Cosimo Sacco, Gennaro Cormio, Enrico Breda, Saverio Cinieri, Donato Natale, Giorgia Mangili, Carmela Pisano, Sabrina Chiara Cecere, Marilena Di Napoli, Vanda Salutari & 8 others Francesco Raspagliesi, Laura Arenare, Alice Bergamini, Jane Bryce, Gennaro Daniele, Maria Carmela Piccirillo, Ciro Gallo, Francesco Perrone

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Abstract

Purpose Platinum-based chemotherapy (PBC) for patients with progressing ovarian cancer (OC) is more effective with a longer time interval from previous platinum treatment (platinum-free interval [PFI]). In 1999, it was hypothesized that prolonging PFI with single-agent non-PBC (NPBC) may offer a strategy to improve overall outcome. MITO-8 aimed to verify this hypothesis commonly used in clinical practice although it has not been prospectively tested. Methods MITO-8 is an open-label, prospective, randomized, superiority trial. Patients with OC who experienced disease progression 6 to 12 months after their last platinum treatment were randomly assigned 1:1 to the experimental sequence of NPBC followed by PBC at subsequent relapse or the standard reverse treatment sequence. Overall survival (OS) was the primary end point. Results Two hundred fifteen patients were enrolled (standard arm [n = 108]; experimental arm [n = 107]). The trial ended before planned because of slow enrollment. PFI was prolonged in the experimental arm (median, 7.8 v 0.01 months). There was no OS benefit in the experimental arm (median, 21.8 v 24.5 months; hazard ratio, 1.38; 95% CI, 0.99 to 1.94; P = .06). Progression-free survival after the sequence was significantly shorter in the experimental arm (median, 12.8 v 16.4 months; hazard ratio, 1.41; 95% CI, 1.04 to 1.92; P = .025). Global quality-of-life change after three cycles was worse in the experimental arm. Slight differences were observed in the incidence of adverse effects. Conclusion MITO-8 supports the recommendation that PBC not be delayed in favor of an NPBC in patients with partially platinum-sensitive OC. PBC should be used as a control arm in future trials of new drugs in this setting.

Original languageEnglish
Pages (from-to)JCO2017734293
JournalJournal of Clinical Oncology
DOIs
Publication statusPublished - Oct 2017

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Platinum
Ovarian Neoplasms
Randomized Controlled Trials
Drug Therapy
Survival
Disease-Free Survival
Disease Progression
Therapeutics
Quality of Life
Recurrence
Incidence

Keywords

  • Journal Article

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Randomized Controlled Trial Testing the Efficacy of Platinum-Free Interval Prolongation in Advanced Ovarian Cancer : The MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG Study. / Pignata, Sandro; Scambia, Giovanni; Bologna, Alessandra; Signoriello, Simona; Vergote, Ignace B; Wagner, Uwe; Lorusso, Domenica; Murgia, Viviana; Sorio, Roberto; Ferrandina, Gabriella; Sacco, Cosimo; Cormio, Gennaro; Breda, Enrico; Cinieri, Saverio; Natale, Donato; Mangili, Giorgia; Pisano, Carmela; Cecere, Sabrina Chiara; Di Napoli, Marilena; Salutari, Vanda; Raspagliesi, Francesco; Arenare, Laura; Bergamini, Alice; Bryce, Jane; Daniele, Gennaro; Piccirillo, Maria Carmela; Gallo, Ciro; Perrone, Francesco.

In: Journal of Clinical Oncology, 10.2017, p. JCO2017734293.

Research output: Contribution to journalArticle

Pignata, S, Scambia, G, Bologna, A, Signoriello, S, Vergote, IB, Wagner, U, Lorusso, D, Murgia, V, Sorio, R, Ferrandina, G, Sacco, C, Cormio, G, Breda, E, Cinieri, S, Natale, D, Mangili, G, Pisano, C, Cecere, SC, Di Napoli, M, Salutari, V, Raspagliesi, F, Arenare, L, Bergamini, A, Bryce, J, Daniele, G, Piccirillo, MC, Gallo, C & Perrone, F 2017, 'Randomized Controlled Trial Testing the Efficacy of Platinum-Free Interval Prolongation in Advanced Ovarian Cancer: The MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG Study', Journal of Clinical Oncology, pp. JCO2017734293. https://doi.org/10.1200/JCO.2017.73.4293
Pignata, Sandro ; Scambia, Giovanni ; Bologna, Alessandra ; Signoriello, Simona ; Vergote, Ignace B ; Wagner, Uwe ; Lorusso, Domenica ; Murgia, Viviana ; Sorio, Roberto ; Ferrandina, Gabriella ; Sacco, Cosimo ; Cormio, Gennaro ; Breda, Enrico ; Cinieri, Saverio ; Natale, Donato ; Mangili, Giorgia ; Pisano, Carmela ; Cecere, Sabrina Chiara ; Di Napoli, Marilena ; Salutari, Vanda ; Raspagliesi, Francesco ; Arenare, Laura ; Bergamini, Alice ; Bryce, Jane ; Daniele, Gennaro ; Piccirillo, Maria Carmela ; Gallo, Ciro ; Perrone, Francesco. / Randomized Controlled Trial Testing the Efficacy of Platinum-Free Interval Prolongation in Advanced Ovarian Cancer : The MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG Study. In: Journal of Clinical Oncology. 2017 ; pp. JCO2017734293.
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abstract = "Purpose Platinum-based chemotherapy (PBC) for patients with progressing ovarian cancer (OC) is more effective with a longer time interval from previous platinum treatment (platinum-free interval [PFI]). In 1999, it was hypothesized that prolonging PFI with single-agent non-PBC (NPBC) may offer a strategy to improve overall outcome. MITO-8 aimed to verify this hypothesis commonly used in clinical practice although it has not been prospectively tested. Methods MITO-8 is an open-label, prospective, randomized, superiority trial. Patients with OC who experienced disease progression 6 to 12 months after their last platinum treatment were randomly assigned 1:1 to the experimental sequence of NPBC followed by PBC at subsequent relapse or the standard reverse treatment sequence. Overall survival (OS) was the primary end point. Results Two hundred fifteen patients were enrolled (standard arm [n = 108]; experimental arm [n = 107]). The trial ended before planned because of slow enrollment. PFI was prolonged in the experimental arm (median, 7.8 v 0.01 months). There was no OS benefit in the experimental arm (median, 21.8 v 24.5 months; hazard ratio, 1.38; 95{\%} CI, 0.99 to 1.94; P = .06). Progression-free survival after the sequence was significantly shorter in the experimental arm (median, 12.8 v 16.4 months; hazard ratio, 1.41; 95{\%} CI, 1.04 to 1.92; P = .025). Global quality-of-life change after three cycles was worse in the experimental arm. Slight differences were observed in the incidence of adverse effects. Conclusion MITO-8 supports the recommendation that PBC not be delayed in favor of an NPBC in patients with partially platinum-sensitive OC. PBC should be used as a control arm in future trials of new drugs in this setting.",
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author = "Sandro Pignata and Giovanni Scambia and Alessandra Bologna and Simona Signoriello and Vergote, {Ignace B} and Uwe Wagner and Domenica Lorusso and Viviana Murgia and Roberto Sorio and Gabriella Ferrandina and Cosimo Sacco and Gennaro Cormio and Enrico Breda and Saverio Cinieri and Donato Natale and Giorgia Mangili and Carmela Pisano and Cecere, {Sabrina Chiara} and {Di Napoli}, Marilena and Vanda Salutari and Francesco Raspagliesi and Laura Arenare and Alice Bergamini and Jane Bryce and Gennaro Daniele and Piccirillo, {Maria Carmela} and Ciro Gallo and Francesco Perrone",
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TY - JOUR

T1 - Randomized Controlled Trial Testing the Efficacy of Platinum-Free Interval Prolongation in Advanced Ovarian Cancer

T2 - The MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG Study

AU - Pignata, Sandro

AU - Scambia, Giovanni

AU - Bologna, Alessandra

AU - Signoriello, Simona

AU - Vergote, Ignace B

AU - Wagner, Uwe

AU - Lorusso, Domenica

AU - Murgia, Viviana

AU - Sorio, Roberto

AU - Ferrandina, Gabriella

AU - Sacco, Cosimo

AU - Cormio, Gennaro

AU - Breda, Enrico

AU - Cinieri, Saverio

AU - Natale, Donato

AU - Mangili, Giorgia

AU - Pisano, Carmela

AU - Cecere, Sabrina Chiara

AU - Di Napoli, Marilena

AU - Salutari, Vanda

AU - Raspagliesi, Francesco

AU - Arenare, Laura

AU - Bergamini, Alice

AU - Bryce, Jane

AU - Daniele, Gennaro

AU - Piccirillo, Maria Carmela

AU - Gallo, Ciro

AU - Perrone, Francesco

PY - 2017/10

Y1 - 2017/10

N2 - Purpose Platinum-based chemotherapy (PBC) for patients with progressing ovarian cancer (OC) is more effective with a longer time interval from previous platinum treatment (platinum-free interval [PFI]). In 1999, it was hypothesized that prolonging PFI with single-agent non-PBC (NPBC) may offer a strategy to improve overall outcome. MITO-8 aimed to verify this hypothesis commonly used in clinical practice although it has not been prospectively tested. Methods MITO-8 is an open-label, prospective, randomized, superiority trial. Patients with OC who experienced disease progression 6 to 12 months after their last platinum treatment were randomly assigned 1:1 to the experimental sequence of NPBC followed by PBC at subsequent relapse or the standard reverse treatment sequence. Overall survival (OS) was the primary end point. Results Two hundred fifteen patients were enrolled (standard arm [n = 108]; experimental arm [n = 107]). The trial ended before planned because of slow enrollment. PFI was prolonged in the experimental arm (median, 7.8 v 0.01 months). There was no OS benefit in the experimental arm (median, 21.8 v 24.5 months; hazard ratio, 1.38; 95% CI, 0.99 to 1.94; P = .06). Progression-free survival after the sequence was significantly shorter in the experimental arm (median, 12.8 v 16.4 months; hazard ratio, 1.41; 95% CI, 1.04 to 1.92; P = .025). Global quality-of-life change after three cycles was worse in the experimental arm. Slight differences were observed in the incidence of adverse effects. Conclusion MITO-8 supports the recommendation that PBC not be delayed in favor of an NPBC in patients with partially platinum-sensitive OC. PBC should be used as a control arm in future trials of new drugs in this setting.

AB - Purpose Platinum-based chemotherapy (PBC) for patients with progressing ovarian cancer (OC) is more effective with a longer time interval from previous platinum treatment (platinum-free interval [PFI]). In 1999, it was hypothesized that prolonging PFI with single-agent non-PBC (NPBC) may offer a strategy to improve overall outcome. MITO-8 aimed to verify this hypothesis commonly used in clinical practice although it has not been prospectively tested. Methods MITO-8 is an open-label, prospective, randomized, superiority trial. Patients with OC who experienced disease progression 6 to 12 months after their last platinum treatment were randomly assigned 1:1 to the experimental sequence of NPBC followed by PBC at subsequent relapse or the standard reverse treatment sequence. Overall survival (OS) was the primary end point. Results Two hundred fifteen patients were enrolled (standard arm [n = 108]; experimental arm [n = 107]). The trial ended before planned because of slow enrollment. PFI was prolonged in the experimental arm (median, 7.8 v 0.01 months). There was no OS benefit in the experimental arm (median, 21.8 v 24.5 months; hazard ratio, 1.38; 95% CI, 0.99 to 1.94; P = .06). Progression-free survival after the sequence was significantly shorter in the experimental arm (median, 12.8 v 16.4 months; hazard ratio, 1.41; 95% CI, 1.04 to 1.92; P = .025). Global quality-of-life change after three cycles was worse in the experimental arm. Slight differences were observed in the incidence of adverse effects. Conclusion MITO-8 supports the recommendation that PBC not be delayed in favor of an NPBC in patients with partially platinum-sensitive OC. PBC should be used as a control arm in future trials of new drugs in this setting.

KW - Journal Article

U2 - 10.1200/JCO.2017.73.4293

DO - 10.1200/JCO.2017.73.4293

M3 - Article

SP - JCO2017734293

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

ER -