Trabectedin plus pegylated liposomal doxorubicin in patients with disease progression after PARP inhibitor maintenance: a real-life case–control study

Abstract

ObjectivePoly (ADP-ribose) polymerase (PARP) inhibitor resistance is problematic in epithelial ovarian cancer management and sequencing strategies may be performed to overcome this issue. In this context, our study evaluated the role of non-platinum doublet pegylated liposomal doxorubicin/trabectedin in ovarian cancer platinum-sensitive patients who experienced disease progression under PARP inhibitor maintenance.MethodsThis case–control study includes patients with recurrent epithelial ovarian cancer treated between March 2016 and April 2021 who progressed under PARP inhibitor maintenance. Data of patients treated with pegylated liposomal doxorubicin/trabectedin (experimental group) were matched 1:1 with a series of patients who received platinum-based treatment (control group). The study outcomes were overall clinical benefit (including complete, partial, and stable response), progression-free survival, and overall survival. The safety of both treatments was also evaluated.ResultsA total of 26 patients in both groups were analyzed. Clinical benefit was achieved in 15 (57%) patients in the study group and 17 (65%) patients in the control group (p=0.38). Patients receiving pegylated liposomal doxorubicin/trabectedin had 5 months of progression-free survival, compared with 5 months in patients treated with platinum-based treatment (p=0.62). Patients in the experimental group achieved a median overall survival of 16 months compared with 19 months in the control group (p=0.26) There was no difference concerning severe toxicities (G3-G4) between groups, except for hepatic toxicity, which was experienced in 30% of the patients receiving pegylated liposomal doxorubicin/trabectedin and none in the control group (p<0.009).ConclusionsPegylated liposomal doxorubicin/trabectedin might be an alternative option to platinum-based treatment in patients experiencing disease progression during PARP inhibitor maintenance with an acceptable toxicity profile. This might be a therapeutic option in this setting, sparing platinum compounds for subsequent relapse.

MITO39: Efficacy and Tolerability of Pegylated Liposomal Doxorubicin (PLD)–Trabectedin in the Treatment of Relapsed Ovarian Cancer after Maintenance Therapy with PARP Inhibitors—A Multicenter Italian Trial in Ovarian Cancer Observational Case-Control Study

“…Interestingly, previous data have shown that PLD + Trabectedin after PARP inhibitors achieves similar oncological outcomes compared with a platinum-based regimen [ 28 ]. Therefore, in a sequence strategy, PLD + Trabectedin still remains a reasonable choice following PARP inhibitors progression, sparing platinum compound for subsequent recurrence.…”

Focus on Trabectedin in Ovarian Cancer: What Do We Still Need to Know?

“…This study suggests that a combination of trabectedin/PLD might be as effective as a platinum-based, both in terms of PFS and OS, with acceptable toxicity profiles on both sides. 50 …”

Poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer: lessons learned and future directions

“…The MITO-8 trial demonstrated that treating patients with a platinum-free interval of 6–12 months with a non-platinum-based regimen before re-introducing platinum did not improve survival,35 but this scenario could change in the post-introduction of PARPi era. Moreover, the pegylated liposomal doxorubicin–trabectedin doublet should be further evaluated in the subgroup of patients with a platinum-free interval of 6–12 months as the results from the INOVATYON trial could be reversed after the advent of PARPi in the first-line setting 36 37. At least theoretically, not only non-platinum agents could be more effective than expected as second-line treatment in patients who progress after PARPi, but the interposition of non-platinum-based chemotherapy may help overcome cross-resistance and possibly improve the response to subsequent platinum-based therapy.…”