Yondelis Approved for Treatment of Soft Tissue Sarcomas

leiomyosarcoma under microscopeA recent survey of treatment of soft tissue sarcomas (STS) makes the point that differentiation of the different types of STS by its appearance under the microscope (50 subtypes have been found) leads to better results in chemotherapy . That is to say that not all cases of STS respond to the same chemotherapy agents in the same way.

The drug Yondelis ( Trabectedin) has been around for about a decade. Initially identified as a chemical released by the sea squrt, it took about a ton of sea squirts to make a small amount of the drug. Fortunately biochemists were able to synthesize the drug saving one researcher the necessity of going to the West Indies with scuba gear to harvest the animals. Initially applied as a ‘one treatment fits all’ approach to sarcoma were disappointing. It has been available in about 70 countries but not the US because of lack of convincing evidence of its efficacy. A third application to the FDA by Johnson and Johnson has achieved approval by the FDA in October, 2015 for limited use in just two types of STS, Leiomyosarcoma, and Liposarcoma with some limitations in regard to which drugs had already been used.

Eventually tumor typing will include genetic screening of the tumor to identify specific gene abnormalities that work to increase cancer growth, thus leading in time to medications directed at specific gene abnormalities.

The FDA news release commented on the most common side effects which included nausea, vomiting, loss of appetite, but most significantly a warning about blood stream infections which could be severe or fatal, muscle tissue breakdown, and liver damage. Cardiac heart function monitoring during treatment is recommended in the product insert, but the risk of heart failure is low. A study from Spain was terminated because the combination of Yondelis with Doxorubicin had poorer effects than with Doxorubicin by itself. A study from France (Lancet Oncology, 2015 Apr: 16(4):457-64) using the same drug combinations but restricted to Leiomyosarcoma, and Liposarcoma showed benefit, but not possible to compare this study with the one from Spain because the one from Spain did not list treatment dosages. A phase 1 trial (used to evaluate different doses of the medication) from Germany (Mar Drugs: 2015 Jan 13;13(1) 379-88 combined Gemcitabine with Yondelis and found dose limiting toxicity with both doses of Yondelis and the trial was stopped.

Based on articles from France and Germany as well as the Johnson and Johnson study this drug seems to have use in these two types of sarcoma and will add to the small list of drugs that have good results. Dosing is giving over 24 hours. The drug’s’ risk profile is significant, however, the side effects are really no worse than other chemotherapy on average. The FDA labeling comments about this.

Story by Dr Larry Seymour MD, RISF Board

Additional Information:

1- Yondelis website (Janssen Pharmaceuticals)
2- FDA announcement:
3- Cancer Research from UK
4- Earlier release (Johnson and Johnson)