Patricia Pautier, MD, head of the Medical Day Hospital Unit at the Institut Gustave Roussy Cancer Campus, discusses the results of the phase 2 LMS-02 trial with doxorubicin and trabectedin (Yondelis) in ​uterine and soft tissue leiomyosarcoma.

The secondary end point of the LMS-02 study was to evaluate overall survival (OS) after a medium follow-up of 7 years, says Pautier. The updated results were encouraging, reflecting a median OS of about 34.4 months in the entire population. The results were less impressive in patients with uterine leiomyosarcoma with a median OS of 27.5 months, adds Pautier. However, the median OS was 38.7 months in patients with soft tissue leiomyosarcoma.

Additionally, two phase 3 studies that were done in the first-line setting in the same patient population showed a median OS ranging from 22 to 29 months with doxorubicin alone or doxorubicin in combination with another agent in patients with soft tissue sarcoma, adds Pautier.

Now, a phase 3 study (NCT02997358) is comparing doxorubicin alone versus the combination of doxorubicin and trabectedin followed by trabectedin in patients who do not progress after 6 cycles of treatment. The results from this research are pending and will be read out soon, concludes Pautier.

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Patricia Pautier, MD, discusses the results of the phase 2 LMS-02 trial with doxorubicin and trabectedin in ​uterine and soft tissue leiomyosarcoma. 

Dr. Pautier on Results of the LMS-02 Trial in Uterine and Soft Tissue Sarcomas

Patricia Pautier, MD, head of the Medical Day Hospital Unit at the Institut Gustave Roussy Cancer Campus, discusses limitations in leiomyosarcoma.

Leiomyosarcoma is a rare disease. As such, developing effective therapies continues to be a major challenge, says Pautier.

Historically, immunotherapy, whether used in combination with doxorubicin or alone, has not shown much activity in this patient population.

Similar to soft tissue sarcomas, oftentimes, uterine leiomyosarcomas will express hormonal receptors. As such, future research efforts should focus on adding targeted therapies to the armamentarium, Pautier concludes.

Patricia Pautier, MD, discusses limitations in leiomyosarcoma.

 Dr. Pautier on Challenges With Drug Development in Leiomyosarcoma 

Patricia Pautier, MD, head of the Medical Day Hospital Unit at the Institut Gustave Roussy Cancer Campus, discusses remaining challenges in treating patients with metastatic/advanced uterine and soft tissue leiomyosarcoma.

The main challenge with treating patients with advanced soft tissue leiomyosarcomas is that there isn't a specific target or molecular alteration for investigators to focus on, says Pautier. Therefore, no other therapies have been made available beyond chemotherapy, explains Pautier. 

A goal is to enhance the survival of patients in the first-line setting, and to develop drugs other than standard chemotherapy, adds Pautier. In this particular disease, it is difficult to conduct specific studies because of the different histologic subtypes. Response rates and the evolution of disease vary between subtypes. As such, specific studies must be dedicated to examining drugs in specific histologic subtypes in order to progress the field, according to Pautier.

It is difficult to gain access to drugs in this rare disease and to conduct randomized studies. The field will have to conduct international studies to achieve responses more rapidly, concludes Pautier.

Patricia Pautier, MD, discusses remaining challenges in treating patients with metastatic/advanced uterine and soft tissue leiomyosarcoma.

Dr. Pautier on Remaining Challenges in Advanced Soft Tissue Sarcoma

Patricia Pautier, MD, head of the Medical Day Hospital Unit at the Institut Gustave Roussy Cancer Campus, discusses the rationale for the phase 2 LMS-02 trial in ​uterine and soft tissue leiomyosarcoma. 

Soft tissue sarcomas are rare and ​relatively heterogeneous malignancies, Pautier explains. ​Some subtypes, such as leiomyosarcoma, are associated with poor prognosis​ and therefore, have limited studies dedicated to ​them.

The LMS-02 trial evaluated the safety and efficacy of doxorubicin in combination with trabectedin in patients with metastatic ​or ​advanced uterine and soft tissue leiomyosarcoma.

To date, the ​first-line standard of care for this patient population is doxorubicin alone, Pautier concludes. 

Patricia Pautier, MD, discusses the rationale for the phase 2 LMS-02 trial in ​uterine and soft tissue leiomyosarcoma. 

Dr. Pautier on the Rationale for the LMS-02 Trial in Soft Tissue Sarcoma 

Patricia Pautier, MD, head of the Medical Day Hospital Unit at the Institut Gustave Roussy Cancer Campus, discusses the toxicity profile of doxorubicin with trabectedin in the phase 2 LMS-02 trial in patients with metastatic/advanced uterine and soft tissue leiomyosarcoma.

Doxorubicin in combination with trabectedin has a high rate of hematologic toxicity, but this is manageable throughgranulocyte colony-stimulating factor, says Pautier. There was no toxic death observed in the study, according to Pautier. Patients were offered the possibility of surgery after 6 cycles of therapy.

One-quarter of patients in both groups can benefit from surgery with better results in terms of progression-free survival and overall survival, specifically those who undergo surgery after 6 cycles of therapy. The enhancement of response rates potentially permit more surgery in this particular patient population with locally advanced or metastatic disease, concludes Pautier.

Patricia Pautier, MD, discusses the toxicity profile of doxorubicin with trabectedin in the phase 2 LMS-02 trial in patients with metastatic/advanced uterine and soft tissue leiomyosarcoma.

Patricia Pautier, MD

Articles

Dr. Pautier on Results of the LMS-02 Trial in Uterine and Soft Tissue Sarcomas

Dr. Pautier on Challenges With Drug Development in Leiomyosarcoma

Dr. Pautier on Remaining Challenges in Advanced Soft Tissue Sarcoma

Dr. Pautier on the Rationale for the LMS-02 Trial in Soft Tissue Sarcoma

Dr. Pautier on Doxorubicin Plus Trabectedin in Soft Tissue Sarcoma