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

Figures & data

Figure 1 Mechanisms of action of trabectedin on the TME.

Notes: Trabectedin selectively induces apoptosis in TAMs and reduces the levels of specific inflammatory mediators (CCL2, IL-6, CXCL8). Additionally, trabectedin decreases neoangiogenesis and enhances T-cell infiltration.

Abbreviations: TAMs, Tumor-associated Macrophages; TME, Tumor Microenvironment.

Table 1 Trabectedin/PLD in Platinum-Sensitive ROC

Trial Information	Study Design	Number Patients	Trabectedin/PLD Line of Treatment	PFS Months	OS Months	ORR %
OVA-301 (NCT00113607) Monk et al, 2010^Citation12	Randomized, controlled phase III trial	218	Second line in all pts	9.2	27	35.2
OVC-3006 (NCT01846611) Monk et al, 2020^Citation35	Randomized, controlled phase III trial	172	Third line in all patients	10	24.7	54.1
INOVATYON (NCT01379989) Colombo et al, 2023^Citation36	Randomized, controlled phase III trial	227	Second line in 69.4% of pts Third line in 30.6% of pts	7.5	21.9	/
NIMES-ROC (NCT02825420) Pignata et al, 2021^Citation37	Non-interventional prospective phase IV trial	218	≥ third line in all pts	9.5	23.6	37.2

Abbreviations: ORR Overall Response Rate; OS, Overall Survival; PFS Progression-free Survival; PLD, Pegylated Liposomal Doxorubicin; pts, patients.

Table 2 Grade 3 and 4 Adverse Events Trabectedin/PLD Related

TOXICITY	OVA-301 Monk et al, 2010^12				OVC-3006 Monk et al, 2020^35				INOVATYON Colombo et al, 2023^36				NIMES-ROC Pignata et al, 2021^37
	Grade 3		Grade 4		Grade 3		Grade 4		Grade 3		Grade 4		Grade 3		Grade 4
	Np	%	Np	%	Np	%	Np	%	Np	%	Np	%	Np	%	Np	%
Anemia	31	9.3	10	3.0	61	21.3	0	0	11	3.6	1	0.3	14	6.4	0	0
Leukopenia	82	24.6	28	8.4	32	11.2	9	3.1	14	4.6	8	2.6	7	3.2	2	0.9
Neutropenia	96	28.8	113	33.9	47	16.4	77	26.9	62	21.1	56	18.4	37	17	29	13.3
Thrombocytopenia	34	10.2	27	8.1	22	7.7	21	7.3	14	4.6	9	3.0	8	3.7	4	1.8
Nausea	29	8.7	0	0	21	7.3	0	0	27	8.9	1	0.3	NA	NA	NA	NA
Vomiting	33	9.9	1	0.3	18	6.3	0	0	20	6.6	0	0	8	3.7	0	0
Fatigue	19	5.7	1	0.3	31	10.8	0	0	0	0	0	0	11	5.0	0	0
Stomatitis	3	0.9	0	0	5	1.7	0	0	7	2.3	1	0.3	NA	NA	NA	NA
ALT increase	21	28.5	3	2.4	94	32.9	12	4.2	48	15.8	10	3.3	NA	NA	NA	NA
AST increase	95	6.3	8	0.9	23	8.0	5	1.7					NA	NA	NA	NA

Abbreviations: ALT, alanine amino transferase; AST aspartate amino transferase; NA; not available; Np, number patients.

Figure 2 Possible scenarios of treatment with trabectedin/PLD for ROC.

Notes: For practicality and clarity, the figure depicts the first, second, or third relapses. However, trabectedin/PLD may be administered at any relapse with TFIp >6 months, provided that the combination has not been previously employed. *Due to contraindications to platinum-based treatment (hypersensitivity and/or residual toxicity). ^§Bevacizumab may not be allowed after first recurrence in some countries according to local regulations.

Abbreviations: Bev, Bevacizumab; ChT, Chemotherapy; PARPi, Poly (ADP-ribose) polymerase inhibitors; PLD, Pegylated Liposomal Doxorubicin; ROC, Recurrent Ovarian Cancer; TFIp, Treatment-Free Interval from last Platinum; trab, Trabectedin.

Monk BJ, Herzog TJ, Kaye SB, et al. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol. 2010;28(19):3107–3114. doi:10.1200/JCO.2009.25.4037

 PubMed Web of Science ®Google Scholar

Monk BJ, Herzog TJ, Wang G, et al. A phase 3 randomized, open-label, multicenter trial for safety and efficacy of combined trabectedin and pegylated liposomal doxorubicin therapy for recurrent ovarian cancer. Gynecol Oncol. 2020;156(3):535–544. doi:10.1016/j.ygyno.2019.12.043

 PubMed Web of Science ®Google Scholar

Colombo N, Gadducci A, Sehouli J, et al.; INOVATYON study group. INOVATYON/ ENGOT-ov5 study: randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6–12 months after last platinum line. Br J Cancer. 2023;128(8):1503–1513. doi:10.1038/s41416-022-02108-7

 PubMed Web of Science ®Google Scholar

Pignata S, Scambia G, Villanucci A, et al. A European, Observational, Prospective Trial of trabectedin plus pegylated liposomal doxorubicin in patients with platinum-sensitive ovarian cancer. Oncologist. 2021;26(4):e658–e668. doi:10.1002/onco.13630

 PubMed Web of Science ®Google Scholar