Real-World Management of Trabectedin/Pegylated Liposomal Doxorubicin in Platinum-Sensitive Recurrent Ovarian Cancer Patients: A National Survey

Ferrandina, Gabriella; Amadio, Giulia; Paris, Ida; Distefano, Mariagrazia; Palluzzi, Eleonora; Vincenzo, Rosa De; Ricci, Caterina; Scambia, Giovanni

doi:10.1097/igc.0000000000001058

Cited by 3 publications

(4 citation statements)

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“…Following the initial approval of trabectedin in 2007, being the first ever marine-derived antineoplastic drug approved (Demetri et al 2009 ), based on the results from a phase III randomized OVA-301 study (ClinicalTrials.gov Identifier: NCT00113607), which compared pegylated liposomal doxorubicin (PLD) alone with the combination of PLD and trabectedin in patients with ROC, in 2009 trabectedin plus PLD obtained the second marketing authorization for the treatment of patients with platinum-sensitive ROC (Monk et al 2010 ). According with the recent survey carried out in Italy about the real-world management of trabectedin plus PLD in patients with platinum-sensitive ROC, currently, among the non-platinum/non-taxane treatments, this combination is the most frequently adopted regimen in such patients (Ferrandina et al 2017 ). Particularly for patients suffering from platinum-induced toxicities or hypersensitivity, patients who had received more than one platinum-based chemotherapy or patients with partially platinum-sensitive disease who can benefit from a delay in platinum re-treatment (Poveda et al 2014 ) the combination of trabectedin plus PLD represents an alternative in treating patients with platinum-sensitive relapse.…”

Section: Introductionmentioning

confidence: 99%

Trabectedin plus pegylated liposomal doxorubicin (PLD) for patients with platinum-sensitive recurrent ovarian cancer: a prospective, observational, multicenter study

Runnebaum

Reichert

Ringsdorf³

et al. 2018

J Cancer Res Clin Oncol

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PurposeThe OVA-YOND study is the first prospective, non-interventional trial designed to evaluate trabectedin (1.1 mg/m2) plus PLD (30 mg/m2) in patients with platinum-sensitive recurrent ovarian cancer (ROC), given according to the marketing authorization in real-life clinical practice across Germany.MethodsEligible patients were adults with platinum-sensitive ROC, pretreated with ≥ 1 platinum-containing regimen/s. The primary endpoint was to assess safety/tolerability of the combination.ResultsSeventy-seven patients with platinum-sensitive relapse from 31 sites were evaluated. Patients received a median of 6 cycles (range 1–21) with 39 patients (50.6%) receiving ≥ 6 cycles. Median treatment duration was 4.2 months (range 0.7–18.8), mostly on an outpatient basis (88.3% of patients). Most common grade 3/4 trabectedin-related adverse events (AEs) were leukopenia (18.2%), neutropenia (15.6%), thrombocytopenia (9.1%), alanine (7.8%) and aspartate aminotransferase (6.5%) increase, and nausea/vomiting (5.2% each). Neutropenia (18.2%), leukopenia (15.6%), thrombocytopenia (10.4%), and nausea/vomiting (5.2% each) were the most frequent grade 3/4 PLD-related AEs. No deaths attributed to drug-related AEs or unexpected AEs occurred. Five patients (6.5%) had a complete response and 19 patients (24.7%) achieved a partial response for an objective response rate of 31.2% with median response duration of 6.25 months. Sixteen patients (20.8%) had disease stabilization for a disease control rate of 51.9%. Median progression-free survival was 6.3 months and median overall survival was 16.4 months.ConclusionTrabectedin plus PLD confer clinically meaningful benefit to pre-treated patients with platinum-sensitive ROC, being comparable to those previously observed in selected populations from clinical trials and with a manageable safety profile.

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Section: Introductionmentioning

confidence: 99%

Trabectedin plus pegylated liposomal doxorubicin (PLD) for patients with platinum-sensitive recurrent ovarian cancer: a prospective, observational, multicenter study

Runnebaum

Reichert

Ringsdorf³

et al. 2018

J Cancer Res Clin Oncol

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“…Pegylated liposomal doxorubicin (PLD) is widely administered to platinum‐refractory/resistant EOC patients 9 . However, the response rate of platinum‐refractory/resistant EOC to PLD is not high (approximately 10%–20%), while PLD causes a variety of adverse events including cardiotoxicity and hand‐foot syndrome 9–12 . Because only a subset of patients with platinum‐refractory/resistant EOC respond to PLD, predicting which patients will benefit from PLD is critical to avoid ineffective chemotherapy and unnecessary adverse events.…”

Section: Introductionmentioning

confidence: 99%

“… 9 However, the response rate of platinum‐refractory/resistant EOC to PLD is not high (approximately 10%–20%), while PLD causes a variety of adverse events including cardiotoxicity and hand‐foot syndrome. 9 , 10 , 11 , 12 Because only a subset of patients with platinum‐refractory/resistant EOC respond to PLD, predicting which patients will benefit from PLD is critical to avoid ineffective chemotherapy and unnecessary adverse events. Therefore, a biomarker that predicts the efficacy of PLD is strongly needed in the clinical practice of gynecologic oncology.…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue area is a predictive biomarker for the efficacy of pegylated liposomal doxorubicin in platinum‐refractory/resistant ovarian cancer

Yoshida

2023

Cancer Medicine

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Background Pegylated liposomal doxorubicin (PLD), an anthracycline agent, is widely used as a treatment option for platinum‐refractory/resistant epithelial ovarian cancer (EOC). Although only a subset of patients with platinum‐refractory/resistant EOC derive benefit from PLD, predictive biomarkers for patients who will respond to the drug have not yet been established. Here, we evaluated the relationship between adipose tissue status and PLD efficacy in patients with platinum‐refractory/resistant EOC. Methods Patients with platinum‐refractory/resistant EOC who were treated with single‐agent PLD were included in this retrospective cohort study. Adipose tissue areas including visceral adipose tissue area (VATA), subcutaneous adipose tissue area (SATA), and visceral to subcutaneous adipose tissue area ratio (VSR) were calculated prior to the initiation of PLD using computed tomography images. The associations of adipose tissue areas with objective response rate (ORR) and patient survival were evaluated. Results Forty‐four patients with platinum‐refractory/resistant EOC who received single‐agent PLD were included. Subjects were categorized into high and low groups according to the median VATA, SATA, and VSR values, and body mass index (BMI). The ORR of PLD was significantly lower in the VSR‐high group than in the VSR‐low group (p = 0.0089). Patients in the high VSR group showed significantly shorter progression‐free survival (PFS) compared with patients in the low VSR group (median, 4.0 vs. 8.5 months; p = 0.020). In the multivariable analysis, high VSR was a significant prognostic factor for shorter PFS (hazard ratio, 2.07; 95% confidence interval, 1.05–4.19; p = 0.035). VATA, SATA, and BMI showed no significant association with ORR and survival of patients who received PLD. Conclusions High VSR is associated with lower ORR and shorter PFS in patients with platinum‐refractory/resistant EOC who received single‐agent PLD. VSR is a robust predictive biomarker for the efficacy of PLD.

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“…PLD is one of the preferred drugs due to its favorable toxicity profile (absence of alopecia, limited cardiac toxicity, and only moderate hematological and skin toxicity) [13, 14]. However, response rates range from 16 to 25%.…”

Section: Introductionmentioning

confidence: 99%

TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancers

et al. 2019

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ObjectiveRelapsed epithelial ovarian cancer (EOC) is frequently treated with pegylated liposomal doxorubicin (PLD). Unfortunately, most patients do not benefit from treatment. Prediction of response is crucial to optimize PLD use and avoid unnecessary toxicities. We aimed at assessing the value of topoisomerase II alpha (TOP2A) expression as predictive marker of response to PLD-based therapy in patients with relapsed EOCs.MethodsWe retrospectively analyzed Formalin Fixed Paraffin Embedded (FFPE) tissues from 101 patients with platinum resistant (PR) or partially platinum-sensitive (PPS) EOCs treated with PLD-based chemotherapy beyond second line in three referral cancer centers between January 2010 and June 2018. TOP2A expression was measured by immunohistochemistry (IHC): images of each sample were acquired by optical microscope and analyzed by using automatic counter software. Correlation between TOP2A expression and response to PLD was assessed. Since no cut-off for positivity has been validated yet, we dichotomized TOP2A expression based on a cut-off of 18% (mean value in this study).ResultsTOP2A expression beyond cut-off was not prognostic for primary platinum-free interval in our series (p = 0.77) neither for optimal cytoreduction (p = 0.9). TOP2A > 18% was associated with a longer time to progression (TTP) following PLD-treatment, although not statistically significant (p = 0.394). No difference was observed between PR and PPS patients’ groups (p = 0.445 and p = 0.185, respectively). Not unexpectedly, patients with TOP2A expression > 18% treated with PLD monotherapy achieved a longer TTP compared with PLD-doublet therapy (p = 0.05).ConclusionsOur data suggest that TOP2A status might predict activity of PLD in patients with PR/PPS EOCs.

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Real-World Management of Trabectedin/Pegylated Liposomal Doxorubicin in Platinum-Sensitive Recurrent Ovarian Cancer Patients: A National Survey

Abstract: This survey highlights the gaps in transposing evidence-based or consensus guidelines in the real-world management of T/PLD administration; these findings could be useful in order to focus the attention on specific knowledge and/or experience gaps and plan pertinent educational programs.

Cited by 3 publications

References 30 publications

Trabectedin plus pegylated liposomal doxorubicin (PLD) for patients with platinum-sensitive recurrent ovarian cancer: a prospective, observational, multicenter study

Trabectedin plus pegylated liposomal doxorubicin (PLD) for patients with platinum-sensitive recurrent ovarian cancer: a prospective, observational, multicenter study

Adipose tissue area is a predictive biomarker for the efficacy of pegylated liposomal doxorubicin in platinum‐refractory/resistant ovarian cancer

TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancers

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