Jean-Yves Blay, MD, professor of Medicine, Université Claude Bernard, scientific director, Canceropole Lyon Rhône Alpes, vice chairman, EORTC Translational Research Advisory Committee, member, the Protocol Review Committee of EORTC, chairman, the Soft Tissue and Bone Sarcoma group of EORTC, the French Sarcoma Group, discusses treatment considerations in patients with soft tissue sarcomas.

Neoadjuvant plus adjuvant treatment is recommended for a small fraction of patients with specific characteristics in soft tissue sarcomas, Blay says. However, debates are ongoing about which patients could most benefit from neoadjuvant treatment, Blay adds. For example, patients with large grade 2 and 3 tumors may benefit from neoadjuvant therapy, which typically consists of doxorubicin plus ifosfamide (Ifex), Blay explains.

In the first-line setting for metastatic or relapsed disease, doxorubicin-based therapy is also recommended, Blay continues. Doxorubicin plus dacarbazine can be used for patients with leiomyosarcoma due increased response rates, progression-free survival rates, and overall survival, Blay explains. However, these benefits need to be tested in a randomized clinical trial, Blay concludes.

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Jean-Yves Blay, MD, discusses treatment considerations in patients with soft tissue sarcomas.


Dr. Blay on Treatment Considerations in Soft Tissue Sarcomas

Jean-Yves Blay, MD, professor of Medicine, Université Claude Bernard, scientific director, Canceropole Lyon Rhône Alpes, vice chairman, EORTC Translational Research Advisory Committee, member, the Protocol Review Committee of EORTC, chairman, the Soft Tissue and Bone Sarcoma group of EORTC, the French Sarcoma Group, discusses current treatment challenges in soft tissue sarcomas.

In France, patients with sarcomas or suspected sarcomas are required to undergo a pathology review for soft tissue sarcomas, and this practice has been in place for about 10 years, Blay says. Under this system, all diagnoses of soft tissue sarcoma undergo review and confirmation by an expert pathologist, Blay explains. Each diagnosis also undergoes surgical review and genomic testing when needed, Blay adds.

Because of this process, the main challenge in the soft tissue sarcomas remains in the referral of patients for earlier management of their disease, which is not mandatory, Blay explains. Despite an increase in the quality of care available for these patients, the proportion of patients who are reaching oncologists at a referral center before the first treatment is limited to about 55%, Blay continues. Those 55% of patients tend to have better outcomes than those who are not referred, and more must be done to address the patient population, Blay concludes. 

Jean-Yves Blay, MD, discusses current treatment challenges in soft tissue sarcomas.


Dr. Blay on the Current Treatment Challenges in Soft Tissue Sarcomas

Jean-Yves Blay, MD, professor of Medicine, Université Claude Bernard, scientific director, Canceropole Lyon Rhône Alpes, vice chairman, EORTC Translational Research Advisory Committee, member, the Protocol Review Committee of EORTC, chairman, the Soft Tissue and Bone Sarcoma group of EORTC, the French Sarcoma Group, discusses the exploration of BI 907828 in patients with sarcoma.

BI 907828 is an oral MDM2 inhibitor, and by binding to the MDM2 protein, the agent MDM2 from binding with the tumor suppressor protein, p53.

In preclinical studies, BI 907828 has demonstrated remarkable activity in terms of blocking specific interactions in the cellular pathways, Blay says. Clinical trials have started investigating BI 907828, including a phase 1 trial (NCT03449381) in adults with different types of solid tumors, including sarcomas, to evaluate the most suitable dose of BI 907828 and the agent’s efficacy in various populations.

Prior MDM2 inhibitors have shown the ability to block interactions with the MDM2 protein, though the blockade with BI 907828 appears to be more significant, Blay explains. The level of activity of BI 907828 in MDM2-amplfied tumors has been consistent across preclinical data, Blay adds.

BI 907828 has also displayed higher pharmodynamic activity than other MDM2 inhibitors, though there have been more higher toxicities, Blay notes. However, this agent warrants further investigation in clinical trials, and seeing these studies is good news for patients with these molecular alterations, Blay concludes. 

Jean-Yves Blay, MD, discusses the exploration of BI 907828 in patients with sarcoma.


Dr. Blay on the Exploration of BI 907828 in Patients With Sarcoma

Jean-Yves Blay, MD, PhD, professor of medicine at the Université Claude Bernard, Lyon, France, and the scientific director of the Canceropole Lyon Rhône Alpes, discusses the treatment landscape of sarcoma.

From a clinical research standpoint, it is very difficult to develop trials for sarcoma due to its variability between patients. The rarity of this disease must be adapted to the research of it, says Blay. Sarcoma has been shown to be a good model in which to develop treatments, adds Blay, demonstrated by the success of eribulin (Halaven) in liposarcoma.

Dr. Blay Discusses the Treatment Landscape of Sarcoma

Jean-Yves Blay, MD, PhD, professor of Medicine at the Université Claude Bernard, Lyon, France, and the scientific director of the Canceropole Lyon Rhône Alpes, discusses the heterogeneity of soft tissue sarcoma.

There are more than 80 different histological subtypes of sarcomas, and they have not all yet been explored, Blay explains. This will be a major part of research in the field going forward. Additionally, sarcoma remains to be a be a very difficult-to-treat patient population because it is not a homogenous group of tumors.

Clinical presentation, molecular behavior, and histology are all very different from one another in each of these sarcoma subtypes. These subgroups are also very rare, he adds.

Dr. Blay on the Heterogeneity of Soft Tissue Sarcoma

Jean-Yves Blay, MD, PhD, professor of medicine at the Université Claude Bernard, Lyon, France, and the scientific director of the Canceropole Lyon Rhône Alpes, discusses a subgroup analysis of leiomyosarcoma patients from a phase III study of eribulin compared to dacarbazine (DTIC) in patients with advanced liposarcoma or leiomysosarcoma.

Leiomyosarcoma is a complex and difficult to treat patient population, says Blay. The analysis found that eribulin was equivalent to DTIC in terms of overall survival and progression-free survival in all subgroups of leiomyosarcoma. This is important because leiomyosarcoma is very heterogeneous, says Blay.

DTIC is well known to be a very active agent in leiomyosarcoma, so the observation that eribulin is equivalent is very interesting for the drug, he says.

Eribulin was well tolerated in leiomyosarcoma patients overall.

​Jean-Yves Blay, MD, PhD, professor of medicine at the Université Claude Bernard, Lyon, France, and the scientific director of the Canceropole Lyon Rhône Alpes, discusses a subgroup analysis of leiomyosarcoma patients from a phase III study of eribulin compared to dacarbazine (DTIC) in patients with advanced liposarcoma or leiomysosarcoma.
 

Jean-Yves Blay, MD, PhD

Articles

Dr. Blay on Treatment Considerations in Soft Tissue Sarcomas

Dr. Blay on the Current Treatment Challenges in Soft Tissue Sarcomas

Dr. Blay on the Exploration of BI 907828 in Patients With Sarcoma

Dr. Blay Discusses the Treatment Landscape of Sarcoma

Dr. Blay on the Heterogeneity of Soft Tissue Sarcoma

Dr. Jean-Yves Blay on Eribulin in Leiomyosarcoma