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Clinical Trial
. 2023 Apr;128(8):1503-1513.
doi: 10.1038/s41416-022-02108-7. Epub 2023 Feb 9.

INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line

N Colombo  1 , A Gadducci  2 , J Sehouli  3 , E Rulli  4 , J Mäenpää  5 , C Sessa  6 , A Montes  7 , N B Ottevanger  8 , R Berger  9 , I Vergote  10 , M D'Incalci  4   11 , C Churruca Galaz  12 , R Chekerov  3 , G B Nyvang  13 , S Riniker  14 , R Herbertson  15 , R Fossati  4 , M P Barretina-Ginesta  16 , M Deryal  17 , M R Mirza  18 , E Biagioli  19 , M Iglesias  20 , G Funari  4 , M Romeo  21 , G Tasca  22 , B Pardo  23 , G Tognon  24 , M J Rubio-Pérez  25 , A DeCensi  26 , U De Giorgi  27 , P Zola  28 , P Benedetti Panici  29 , M Aglietta  30 , V Arcangeli  31 , C Zamagni  32 , A Bologna  33 , A Westermann  34 , V Heinzelmann-Schwarz  35 , I Tsibulak  9 , P Wimberger  36   37   38   39   40 , A Poveda  41 ; INOVATYON study group
Collaborators, Affiliations
Clinical Trial

INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line

N Colombo et al. Br J Cancer. 2023 Apr.

Abstract

Background: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC).

Methods: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75).

Results: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP).

Conclusions: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities.

Clinical trial registration: ClinicalTrials.gov, number NCT01379989.

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Conflict of interest statement

EB, ER, GF and RF report grants from PharmaMar to their Institution for the conduct of the study. UG reports personal fees from Pfizer, personal fees from Roche, personal fees from Pharmamar, personal fees from GSK, personal fees from Clovis, personal fees from Astrazeneca, personal fees from Ipsen, personal fees from Astellas, personal fees from Janssen, personal fees from MSD, personal fees from BMS, personal fees from Novartis, personal fees from EISAI, outside the submitted work. MPBG reports personal fees from Roche, personal fees from Astrazeneca, personal fees from Clovis, personal fees from Pharmamar, personal fees from GSK outside the submitted work. GTasca reports personal fees from GSK, personal fees from Clovis Oncology, personal fees from Astrazeneca, outside the submitted work. IV reports personal fees from Agenus (2021), personal fees from Akesobio China (2021), grants and other from Amgen (Europe), GmbH (2019), personal fees and other from AstraZeneca (2019–2022), personal fees from Bristil Myers Squibb (2021), other from Clovis Oncology Inc. (2019–2019), other from Carrick Therapeutics (2019), personal fees and other from Deciphera Pharmaceuticals (2020–2021), personal fees from Eisai (2021), personal fees from Elevar Therapeutics (2020), personal fees and other from F. Hoffmann-La Roche Ltd (2019-2021), grants and other from Genmab (2019-2021), personal fees and other from GSK (2019-2021), personal fees and other from Immunogen Inc. (2019–2022), personal fees from Jazzpharma (2021–2022), personal fees from Karyopharm (2021), personal fees from Mersana (2020), other from Millenium Pharmaceuticals (2019), personal fees and other from MSD (2019–2022), personal fees and other from Nocovure (2020–2022), personal fees from Novartis (2021), other from Octimet Oncology NV (2019), grants, personal fees and other from Oncoinvent AS (2019–2022), personal fees from Seagen (2021), personal fees and other from Sotio a.s. (2019–2022), other from Verastem Oncology (2020), personal fees from Zentalis (2020), grants and other from Roche (2019–2020), outside the submitted work. JM reports personal Payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from GSK, AstraZeneca, Eisai, and MSD. RB reports grants from Istituto di Ricerche Farmacologiche IRCCS, during the conduct of the study; non-financial support from ROCHE, non-financial support from Biocad, outside the submitted work. IT reports speaker’s honorarium from Pharma Mar Austria outside the submitted work. MRM reports grants from Astra Zeneca, grants from GSK, personal fees from Nuvation Bio, personal fees from Merck, personal fees from Karyopharm, personal gees from Sera Prognostic, personal fees from Mersana, outside the submitted work. MD’Incalci reports grants and personal fees from Pharma Mar, s.a. during the conduct of the study. AP reports advisory board, personal financial interest and invited speaker from Astrazeneca, advisory board and personal financial interest from Clovis, advisory board and personal financial interest from GSK, advisory board and personal financial interest from MSD, advisory board and personal financial interest from PharmaMar, advisory board and personal financial interest from Roche, advisory board and personal financial interest from TESARO/GSK, MR reports grants and personal fees from Astrazeneca, grants and personal fees from MSD, grants and personal fees from Clovis, grants and personal fees from GSK, outside the submitted work. PW reports grants and honoraria/advisory board from Amgen, Astrazeneca, Novartis, Pfizer, Roche, Lilly, GSK and MSD outside the submitted work. NC reports fundings from PharmaMar for the submitted work, consulting fees from AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, Roche outside the submitted work, personal Payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from AstraZeneca, Novartis, Clovis Oncology, GSK, MSD/Merck, EISAI outside the submitted work, support for attending meetings and/or travel from Astra Zeneca, GSK outside the submitted work, participation on a Data Safety Monitoring Board or Advisory Board with AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, Roche outside the submitted work. CZ reports grants or contracts from Roche, Eisai, Novartis, Astrazeneca, Pfizer, Pharmamar, Tesaro, Pierre Fabre, Ist. Gentili, Teva, Seagen, Eli Lilly, Celgene, MSD, GSK, Amgen, Daichii, support for attending meetings and/or travel from Roche, Novartis, Pfizer, Pharmamar, Tesaro, Pierre Fabre, Ist. Gentili, Celgene, participation on a Data Safety Monitoring Board or Advisory Board with Roche, Eisai, Novartis, Astrazeneca, Pfizer, Pharmamar, Amgen, Tesaro, QuintilesIms, Eli Lilly, Celgene, MSD, GSK, Daichii, other financial or non-financial interests from Roche, Novartis, Astrazeneca, Pfizer, Amgen, Tesaro, QuintilesIms, MSD, GSK, Daichii. JS reports grants or contracts from Roche Pharma, AstraZeneca, Bayer, Clovis, GlaxoSmith, Lilly, Tesaro, consulting fees from Tesaro, Merck, Pfizer, PharmaMar, Clovis Oncology, AstraZeneca, Roche Pharma, GlaxoSmith, MSD, Eisai, Novocure, Oncoinvent, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Tesaro, GlaxoSmith, PharmaMar, AstraZeneca, Clovis, Bayer, Roche, PharmaMar, Vifor Pharma, Hexal AG, Novartis Pharma. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Consort diagram.
*Informed consent form not signed/ consent to the procession of personal data not signed; ITT intention to treat, QoL quality of life, ST subsequent treatment, PLD pegylated liposomial doxorubicin.
Fig. 2
Fig. 2. Subsequent treatments.
ST subsequent treatment, VEGFi vascular endothelial growth factor inhibitor, PARPi poly ADP-ribose polymerase inhibitors, PLD pegylated liposomial doxorubicin.
Fig. 3
Fig. 3. Kaplan-Meier curves.
a Overall survival; b Progression-free survival; CI confidence interval, HR hazard ratio, KM est Kaplan-Meier estimation.
See this image and copyright information in PMC

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