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Poster Display session 2

3483 - Impact of prior pegylated liposomal doxorubicin (PLD) treatment in recurrent ovarian cancer (ROC): Sub-group analysis from a randomized, open-label study comparing trabectedin (T) and PLD versus PLD alone in ROC (ET743-OVC-3006)

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Ovarian Cancer

Presenters

Bradley Monk

Citation

Annals of Oncology (2019) 30 (suppl_5): v403-v434. 10.1093/annonc/mdz250

Authors

B.J. Monk1, T.J. Herzog2, S. Triantos3, S. Maul4, G. Wang5, M.J. Pontes Valero6, T. McGowan7, W.S. Shalaby8, R.L. Coleman9

Author affiliations

  • 1 Arizona Oncology (us Oncology Network), University of Arizona; Creighton University, 85016 - Phoenix/US
  • 2 University Of Cincinnati Cancer Institute, University of Cincinnati, 45221 - Cincinnati/US
  • 3 Janssen Research & Development, Clinical Research, 776 - Titusville/US
  • 4 Janssen Research & Development, Clinical Research, 08560 - Titusville/US
  • 5 Janssen Research & Development, Clinical Biostatistics, 08869 - Raritan/US
  • 6 Medical Affairs, PharmaMar SA, 28770 - Madrid/ES
  • 7 Oncology Medical Affairs, Janssen Scientific Affairs, LLC, 19044 - Horsham/US
  • 8 Janssen Biotech, Inc, Janssen Scientific Affairs, LLC, 19044 - Horsham/US
  • 9 Gynecologic Oncology And Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 77030-3721 - Houston/US

Resources

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Abstract 3483

Background

Retreatment with PLD in ROC has raised potential concerns of increased toxicity and diminished response rates. This subgroup analysis examined the safety and efficacy of platinum-sensitive patients (pts) with prior PLD therapy who participated in a randomized, open-label study comparing T+PLD vs PLD alone in line 3 ROC.

Methods

Women with advanced-relapsed ROC having responded to 2 lines of platinum-based therapy were enrolled. Pts were randomly assigned 1:1 to T+PLD [T: 1.1 mg/m2, PLD:30 mg/m2, IV, Q3 wks] or PLD [PLD 50 mg/m2, IV, Q4 wks]. The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS) and objective response rate (ORR). Stratification was based on prior PLD use (Y or N), BRCA1/2 mutation, and platinum-free interval (PFI). NCT01846611.

Results

ET743-OVC-3006 was discontinued (1/18/18) after an interim analysis showed that the futility threshold for OS was exceeded. Up to that point, 576 pts were randomized (T+PLD, n = 289; PLD, n = 287). The safety and efficacy, stratified by prior PLD (Y or N), are presented in the table. Between treatment arms, prior PLD use did not influence the ORR (OR:2.064; 95% CI:0.479, 9.073; p = 0.341), PFS (HR:0.626, 95% CI: 0.265, 1.478; p = 0.281), or OS (HR:0.933; 95% CI: 0.335, 2.596; p = 0.894). In addition, within each treatment cohort (Table), prior PLD use did not influence ORR, PFS, or OS. While combination T+PLD, as expected, elicited greater grade 3/4 TEAEs than PLD alone, prior PLD therapy did not appear to impact the incidence of grade 3/4 TEAEs within each treatment arm except for thrombocytopenia for T+PLD (Table).Table: 1030P

Efficacy and safety of T+PLD vs PLD by prior PLD therapy use

T + PLD [n = 289]PLD monotherapy [n = 287]
EfficacyPrior PLDPrior PLD
Yes (n = 19, 6.6%)No (n = 270, 93.4%)HR (95% CI)Yes (n = 20, 7%)No (n = 267, 93%)HR (95% CI)
ORR (%)52.645.61.328 (0.468 – 3.819)35360.959 (0.313 - 2.692)
PFS (months)7.17.50.853 (0.435, 1.671)5.67.41.212 (0.688, 2.135)
OS (months)34.222.10.844 (0.409, 1.740)28.920.90.713 (0.349, 1.458)
SafetyPrior PLDPrior PLD
Yes (n = 19, 6.6%)No (n = 267, 92.4%)Yes (n = 20, 7%)No (n = 262, 91.3%)
Grade 3/4 TEAEs, n (%)18 (94.7)225 (84.3)14 (70)166 (63.4)
Gastrointestinal5 (26.3)50 (18.7)5 (25)50 (19.1)
Nausea3 (15.8)18 (6.7)1 (5)3 (1.1)
Vomiting3 (15.8)15 (5.6)1 (5)4 (1.5)
Diarrhea2 (10.5)3 (1.1)00
Hematologic10 (52.6)152 (56.9)3 (15)75 (28.6)
Anemia4 (21.1)57 (21.3)1 (5)19 (7.3)
Febrile neutropenia2 (10.5)20 (7.5)1 (5)2 (0.8)
Neutropenia7 (36.8)117 (43.8)1 (5)58 (22.1)
Leukopenia3 (15.8)38 (14.2)020 (7.6)
Thrombocytopenia4 (21.1)39 (14.6)03 (1.1)
Skin PPE010 (3.7)2 (10)31 (11.8)
Cardiac---3 (1.1)1 (5)1 (0.4)
EF decreased001 (5)0
Atrial fibrillation---1 (0.4)---1 (0.4)
CHF---1 (0.4)---0

CHF, congestive heart failure; EF, ejection fraction; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PLD, pegylated liposomal doxorubicin; PPE, palmar-plantar erythrodysaesthesia; T, trabectedin; TEAE, treatment-emergent adverse event.

Conclusions

This pre-stratified exploratory analysis suggests that prior treatment with PLD in ROC does not increase the incidence of Grade 3/4 TEAEs or negatively influence ORR, PFS, and OS in patients receiving T+PLD or PLD alone.

Clinical trial identification

NCT01846611.

Editorial acknowledgement

Lakshmi Kasthurirangan, PhD (SIRO Clinpharm Pvt. Ltd.) provided medical writing assistance and Namit Ghildyal, PhD (Janssen Research & Development, LLC) provided editorial support.

Legal entity responsible for the study

The authors.

Funding

Janssen Research & Development, LLC, USA.

Disclosure

B.J. Monk: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Johnson & Johnson; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Clovis; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche/Genentech; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Tesaro; Honoraria (institution), Advisory / Consultancy: AbbVie; Honoraria (institution), Advisory / Consultancy: Advaxis; Honoraria (institution), Advisory / Consultancy: Amgen; Honoraria (institution), Advisory / Consultancy: Biodesix; Honoraria (institution), Advisory / Consultancy: Genmab; Honoraria (institution), Advisory / Consultancy: Gradalis; Honoraria (institution), Advisory / Consultancy: Immunogen; Honoraria (institution), Advisory / Consultancy: Immunomedics; Honoraria (institution), Advisory / Consultancy: Incyte; Honoraria (institution), Advisory / Consultancy: Mateon (formally Oxigene); Honoraria (institution), Advisory / Consultancy: Merck; Honoraria (institution), Advisory / Consultancy: Myriad; Honoraria (institution), Advisory / Consultancy: Perthera; Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Precision Oncology, Puma, Samumed, Takeda, VBL. T.J. Herzog: Advisory / Consultancy: Morphotek, Merck, AstraZeneca, Genentech, and Johnson and Johnson. S. Triantos: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen Research & Development. S. Maul: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen Research & Development. G. Wang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen Research & Development. M.J. Pontes Valero: Full / Part-time employment: PharmaMar SA. T. McGowan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen Scientific Affairs. W.S. Shalaby: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen Scientific Affairs. R.L. Coleman: Honoraria (institution), Research grant / Funding (institution), Served on a DSMB for trabectedin on an unrelated trial: Honoraria and research funding from Johnson & Johnson.

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