Dr Femino on the Need for Adjuvant Targeted Therapies in Chondrosarcoma

"The greatest unmet need [in chondrosarcoma] is the need for adjuvant drug therapy. Chondrosarcomas have traditionally not been responsive to cytotoxic chemotherapies, but…some [promising] targeted therapies recently have recently been identified."

Joseph Dominic Femino, MD, an orthopedic surgeon, as well as a clinical associate professor of Orthopaedic Surgery (Practitioner) and chief of musculoskeletal oncology at Keck School of Medicine of USC, discusses the greatest unmet need in chondrosarcoma management.

Historically, the treatment landscape for this malignancy has been heavily limited by the fact that these tumors are typically resistant to standard cytotoxic chemotherapies, Femino began. Although surgical intervention remains the cornerstone of care, the field is finally transitioning toward a more nuanced, biomarker-driven approach, he stated.

The primary method for achieving a cure in chondrosarcoma continues to be surgical wide resection. According to Femino, the quality of the surgical margin is a vital prognostic indicator for the patient, alongside other variables such as tumor subtype, grade, and disease stage. However, the historical absence of effective adjuvant drug therapies represents the greatest unmet need in the field, particularly for patients presenting with high-grade or metastatic disease that cannot be managed solely through local intervention, he asserted.

Recent advancements in molecular profiling have identified targeted therapies that may finally address this gap, specifically inhibitors targeting mutant isocitrate dehydrogenase, Femino said. One such agent, ivosidenib (Tibsovo), is being evaluated in the phase 3 CHONQUER trial (NCT06127407), which will compare its efficacy with placebo in patients with advanced, high-grade, or metastatic chondrosarcoma.

Overall, the implementation of such targeted agents represents a major shift for a disease that has long relied almost exclusively on local control, Femino said. He concluded that the identification and validation of these drug therapies is the single most important development for improving long-term management and prognosis for patients with chondrosarcoma.