Abstract 830P
Background
Trabectedin/PLD is approved in EU for patients with platinum-sensitive (PS) ROC. Monk et al (Gynecol Oncol 2020; NCT01846611) reported trabectedin/PLD vs PLD results in patients with ROC who progressed ≥6 months after 1st-line platinum and obtained a response to 2nd-line platinum. Based on an interim ad-hoc futility analysis requested by the IDMC, the study stopped early without survival benefit in the combination arm. For the original analysis, 266 events were considered (52% statistical power).
Methods
This post-hoc analysis evaluates the efficacy results (RECIST v.1.1) in the subset of women with a platinum-free interval (PFI) ≥6 months after the last platinum, instead of considering PFI after the first platinum as done in the original analysis.
Results
Overall 333 (57.8%) of patients included in the study had a PFI ≥6 months following the last platinum. Although, trabectedin/PLD did not result in longer survival, there was a trend towards a favorable progression-free survival (PFS), with a 6.4-week prolongation compared to PLD (10.0 vs. 8.4 months) and a significant improvement in objective response rate (ORR: 54.1% vs. 42.2%). Similarly to what was observed in the general population, a marked treatment benefit was observed with trabectedin/PLD in PS patients after last platinum line with a PFI 6-12 months and PS patients with BRCA1/2 mutations [trabectedin/PLD: n=48 vs PLD: n=52; OS: 47.8 vs 20.0 months, Hazard ratio (95% CI): 0.34 (0.17-0.67); PFS: 10.3 vs 7.6 months, 0.61 (0.37-1.02); ORR: 77.1% vs 44.2%, Odds ratio (95% CI): 4.24 (1.65-11.19), p=0.001]. Table: 830P
| Trabectedin / PLD | PLD | Total | |
| PFI after last platinum line, n (%) | n=289 | n=287 | n=576 |
| PFI <6 months | 117 (40.5) | 126 (43.9) | 243 (42.2) |
| PFI ≥6 months | 172 (59.5) | 161 (56.1) | 333 (57.8) |
| PS patients after last platinum line | p | ||
| Median OS, months | |||
| PFI ≥6 months | n=172 | n=161 | |
| 24.7 | 27.9 | ||
| Hazard ratio (95% CI): 0.97 (0.69-1.36) | 0.8621 | ||
| PFI 6-12 months | n=119 | n=111 | |
| 23.0 | 20.9 | ||
| HR (95% CI): 0.84 (0.57-1.24) | 0.3844 | ||
| Median PFS, months | |||
| PFI ≥6 months | n=172 | n=161 | |
| 10.0 | 8.4 | ||
| HR (95% CI): 0.94 (0.71-1.24) | 0.6626 | ||
| PFI 6-12 months | n=119 | n=111 | |
| 10.0 | 7.6 | ||
| HR (95% CI): 0.84 (0.61-1.16) | 0.2914 | ||
| ORR, % | |||
| PFI ≥6 months | n=172 | n=161 | |
| 54.1 | 42.2 | ||
| Odds ratio (95% CI): 1.61 (1.02-2.54) | 0.0371 | ||
| PFI 6-12 months | n=119 | n=111 | |
| 53.8 | 38.7 | ||
| OR (95% CI): 1.84 (1.05-3.22) | 0.0250 |
Conclusions
Among all patients included in the study, only 57.8% were PS after the last platinum, precluding a reliable estimation of PFS or OS. Despite that, there is a trend toward improved PFS combined with significant improvement in ORR with trabectedin/PLD in this subset of patients. More pronounced benefits were observed in PS patients with a PFI 6-12 months and PS patients with BRCA 1/2 mutations.
Clinical trial identification
NCT01846611.
Editorial acknowledgement
Legal entity responsible for the study
Janssen Research & Development.
Funding
This work was funded and supported by Janssen Research & Development. The present sub analysis was performed by PharmaMar.
Disclosure
B.J. Monk: Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen/Johnson&Johnson. T. Herzog: Advisory/Consultancy: AZ Pharmaceutical; Advisory/Consultancy: Caris; Advisory/Consultancy: Clovis; Advisory/Consultancy: Genentech; Advisory/Consultancy: GSK; Advisory/Consultancy: Merck; Advisory/Consultancy: Johnson & Johnson. T. McGowan: Shareholder/Stockholder/Stock options, Full/Part-time employment: Johnson&Johnson. B. De Rivas Otero: Full/Part-time employment: PharmaMar; Shareholder/Stockholder/Stock options, Full/Part-time employment: GSK. J. Gomez: Shareholder/Stockholder/Stock options, Full/Part-time employment: PharmaMar. A. Tanovic: Full/Part-time employment: PharmaMar. R.L. Coleman: Non-remunerated activity/ies, Elect President: IGCS; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Clovis Oncology; Research grant/Funding (self): Esperance; Advisory/Consultancy, Research grant/Funding (self): Genentech-Roche; Advisory/Consultancy, Research grant/Funding (self): Janssen; Advisory/Consultancy, Research grant/Funding (self): Merck; Research grant/Funding (self): OncoMed Pharmaceuticals; Research grant/Funding (self): USA National Cancer Institute; Advisory/Consultancy, Research grant/Funding (self): AbbVie; Advisory/Consultancy: Aravive; Advisory/Consultancy: Curio Science; Advisory/Consultancy: Geistlich; Advisory/Consultancy, Research grant/Funding (self): Genmab; Advisory/Consultancy: MoreHealth; Advisory/Consultancy: GSK; Advisory/Consultancy: Myriad; Advisory/Consultancy: Novocure; Advisory/Consultancy: Roche; Advisory/Consultancy: Tarveda Therapeutics, Inc; Advisory/Consultancy: Tempus Labs, Inc; Advisory/Consultancy: Tesaro; Research grant/Funding (institution): GOG Foundation, Inc.