Trabectedin is genotoxic in both in vitro and in vivo studies. Long-term carcinogenicity studies have not been performed.
Fertility studies with trabectedin were not performed. In male rats there were limited histopathological signs of hemorrhage and degeneration in the testes following repeated administration of trabectedin at doses approximately 0.2 times the 1.5 mg/m2 human dose based on body surface area.
The clinical efficacy and safety of YONDELIS in patients with metastatic or recurrent leiomyosarcoma or liposarcoma were demonstrated in Trial ET743-SAR-3007 (NCT01343277), a randomized (2:1), open-label, active-controlled trial comparing treatment with YONDELIS 1.5 mg/m2 as a 24-hour continuous intravenous infusion once every 3 weeks to dacarbazine 1000 mg/m2 intravenous infusion (20 to 120 minutes) once every 3 weeks. Treatment continued in both arms until disease progression or unacceptable toxicity; all patients in the YONDELIS arm were required to receive dexamethasone 20 mg intravenous injection prior to each YONDELIS infusion. Patients were required to have unresectable, locally advanced or metastatic leiomyosarcoma or liposarcoma (dedifferentiated, myxoid round cell, or pleomorphic) and previous treatment with an anthracycline- and ifosfamide-containing regimen or an anthracycline-containing regimen and one additional cytotoxic chemotherapy regimen. Randomization was stratified by subtype of soft tissue sarcoma (leiomyosarcoma vs. liposarcoma), ECOG performance status (0 vs. 1), and number of prior chemotherapy regimens (1 vs. ≥2). The efficacy outcome measures were investigator-assessed progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), overall survival (OS), objective response rate (ORR), and duration of response (DOR). Patients in the dacarbazine arm were not offered YONDELIS at the time of disease progression.
A total of 518 patients were randomized, 345 to the YONDELIS arm and 173 patients to the dacarbazine arm. The median patient age was 56 years (range: 17 to 81); 30% were male; 76% White, 12% Black, and 4% Asian; 73% had leiomyosarcomas and 27% liposarcomas; 49% had an ECOG PS of 0; and 89% received ≥2 prior chemotherapy regimens. The most common (≥20%) pre-study chemotherapeutic agents administered were doxorubicin (90%), gemcitabine (81%), docetaxel (74%), and ifosfamide (59%). Approximately 10% of patients had received pazopanib.
Trial ET743-SAR-3007 demonstrated a statistically significant improvement in PFS. An exploratory analysis of independent radiology committee-determined PFS, in a subgroup consisting of approximately 60% of the total population, provided similar results to the investigator-determined PFS. Efficacy results from Trial ET743-SAR-3007 are presented in the table below.
|CR=Complete Response; PR=Partial Response; CI=Confidence Interval, HR=hazard ratio, NE=not estimable.|
|PFS Events, n (%)||217 (63%)||112 (65%)|
|Median (95% CI) (months)||4.2 (3.0, 4.8)||1.5 (1.5, 2.6)|
|HR (95% CI)*||0.55 (0.44, 0.70)|
|Overall survival ‡|
|Events, n (%)||258 (67%)||123 (64%)|
|Median (95% CI) (months)||13.7 (12.2, 16.0)||13.1 (9.1, 16.2)|
|HR (95% CI)*||0.93 (0.75, 1.15)|
|Objective Response Rate (ORR: CR+PR)|
|Number of patients (%)||23 (7%)||10 (6%)|
|95% CI §||(4.3, 9.8)||(2.8, 10.4)|
|Duration of Response (CR+ PR)|
|Median (95% CI) (months)||6.9 (4.5, 7.6)||4.2 (2.9, NE)|
Figure 1: Kaplan-Meier Curves of Progression-Free Survival in Trial ET743-SAR-3007
- “OSHA Hazardous Drugs.” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html
YONDELIS is supplied in a single-dose glass vial containing 1 mg trabectedin. Each carton contains one vial (NDC: 59676-610-01).
Storage and Handling
Store YONDELIS vials in a refrigerator at 2°C to 8°C (36°F to 46°F).
YONDELIS is a cytotoxic drug. Follow applicable special handling and disposal procedures.1
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Myelosuppression: Inform patients of the risks of myelosuppression. Instruct patients to immediately contact their healthcare provider for fever or unusual bruising, bleeding, tiredness, or paleness.
Rhabdomyolysis: Advise patients to contact their healthcare provider if they experience severe muscle pain or weakness.
Hepatotoxicity: Advise patients to contact their healthcare provider immediately for yellowing of skin and eyes (jaundice), pain in the upper right quadrant, severe nausea or vomiting, difficulty in concentrating, disorientation, or confusion.
Cardiomyopathy: Advise patients to contact their healthcare provider for new onset chest pain, shortness of breath, fatigue, lower extremity edema, or heart palpitations.
Hypersensitivity: Advise patients to seek immediate medical attention for symptoms of allergic reactions including difficulty breathing, chest tightness, wheezing, severe dizziness or light-headedness, swelling of the lips or skin rash.
Extravasation: Inform patients of the risks of extravasation and to notify their healthcare provider for redness, swelling, itchiness and discomfort or leakage at the injection site.
Capillary leak syndrome: Advise patients to report symptoms such as edema with or without hypotension [see Warnings and Precautions (5.5)].
Embryofetal toxicity: Advise pregnant women of the potential risk to a fetus. Advise females to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment with YONDELIS [see Warnings and Precautions (5.7) and Use in Specific Populations (8.1)].
Females and males of reproductive potential: Advise females of reproductive potential to use effective contraception during treatment with YONDELIS and for at least 2 months after last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with YONDELIS and for at least 5 months after the last dose [see Warnings and Precautions (5.7) and Use in Specific Populations (8.3)].
Lactation: Advise females not to breastfeed during treatment with YONDELIS [see Use in Specific Populations (8.2)].
Product of Spain
Baxter Oncology GmbH
Janssen Products, LP Horsham, PA
© 2015 Janssen Pharmaceutical Companies
Under license from Pharma Mar, S.A.
|PATIENT INFORMATIONYONDELIS® (yon-DEL-ess)(trabectedin)for injection|
|This Patient Information has been approved by the U.S. Food and Drug Administration.||Revised 12/2017|
|What is YONDELIS? YONDELIS is a prescription medicine used to treat people with liposarcoma or leiomyosarcoma that: |
| Who should not receive YONDELIS? |
|What should I tell my healthcare provider before receiving YONDELIS? Before receiving YONDELIS, tell your healthcare provider about all of your medical conditions, including if you: |
| How will I receive YONDELIS? |
|What are the possible side effects of YONDELIS?YONDELIS may cause serious side effects, including: |
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|Tell your healthcare provider if you have any side effect that bothers you or that does not go away.These are not all the possible side effects of YONDELIS. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.|
|General information about the safe and effective use of YONDELIS Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your healthcare provider or pharmacist for information about YONDELIS that is written for health professionals.|
|What are the ingredients in YONDELIS?Active ingredient: trabectedinInactive ingredients: potassium dihydrogen phosphate, sucrose, phosphoric acid and potassium hydroxide.Product of Spain Manufactured by: Baxter Oncology GmbH, Halle/Westfalen Germany Manufactured for: Janssen Products, LP, Horsham, PA For more information, call 1-800-526-7736 or go to www.YONDELIS.com.|
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