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] | |||||
---|---|---|---|---|---|---|
Efficacy | Prior PLD | Prior 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 (%) | 52.6 | 45.6 | 1.328 (0.468 – 3.819) | 35 | 36 | 0.959 (0.313 - 2.692) |
PFS (months) | 7.1 | 7.5 | 0.853 (0.435, 1.671) | 5.6 | 7.4 | 1.212 (0.688, 2.135) |
OS (months) | 34.2 | 22.1 | 0.844 (0.409, 1.740) | 28.9 | 20.9 | 0.713 (0.349, 1.458) |
Safety | Prior PLD | Prior 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) | ||
Gastrointestinal | 5 (26.3) | 50 (18.7) | 5 (25) | 50 (19.1) | ||
Nausea | 3 (15.8) | 18 (6.7) | 1 (5) | 3 (1.1) | ||
Vomiting | 3 (15.8) | 15 (5.6) | 1 (5) | 4 (1.5) | ||
Diarrhea | 2 (10.5) | 3 (1.1) | 0 | 0 | ||
Hematologic | 10 (52.6) | 152 (56.9) | 3 (15) | 75 (28.6) | ||
Anemia | 4 (21.1) | 57 (21.3) | 1 (5) | 19 (7.3) | ||
Febrile neutropenia | 2 (10.5) | 20 (7.5) | 1 (5) | 2 (0.8) | ||
Neutropenia | 7 (36.8) | 117 (43.8) | 1 (5) | 58 (22.1) | ||
Leukopenia | 3 (15.8) | 38 (14.2) | 0 | 20 (7.6) | ||
Thrombocytopenia | 4 (21.1) | 39 (14.6) | 0 | 3 (1.1) | ||
Skin PPE | 0 | 10 (3.7) | 2 (10) | 31 (11.8) | ||
Cardiac | --- | 3 (1.1) | 1 (5) | 1 (0.4) | ||
EF decreased | 0 | 0 | 1 (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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