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)

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

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.