Efficacy and safety of mycophenolate mofetil in patients with high-grade locally advanced or metastatic osteosarcoma (ESMMO): a multicenter, phase II clinical trial.

Background: Osteosarcoma is a prevalent and aggressive bone malignancy primarily affecting young adults. Despite advances in standard treatment, the 5-year survival rate remains low, highlighting the need for new chemotherapy options. Mycophenolate mofetil, an immunosuppressant used post-transplant, has shown promising preclinical anticancer effects in osteosarcoma, warranting further investigation for potential repurpose in humans.

Methods: We conducted this proof-of-concept phase II clinical trial to assess the efficacy and safety of mycophenolate mofetil in high-grade locally advanced or metastatic osteosarcoma. Patients received 3-5 g/day mycophenolate mofetil for four 28-day cycles or until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) at 16 weeks. Secondary endpoints included overall survival (OS), overall response rate, safety, pharmacokinetics, pain score, and quality of life.

Results: Fifteen patients were enrolled. Due to intolerable toxicity at higher doses, most patients received 3 g/day of mycophenolate mofetil. At 16 weeks, the PFS rate was 40%, with only one patient (6.7%) achieving stable disease. Median PFS and OS were 70 and 301 days, respectively. The most common grade 3-4 adverse events were anemia and fatigue, each occurring in 20% of patients. Pharmacokinetic analysis revealed high interindividual variability.

Conclusion: Although mycophenolate mofetil at 3 g/day was well tolerated, it did not meet expectations for anticancer efficacy in patients with high-grade locally advanced or metastatic osteosarcoma. This study should be considered a negative trial. Further research is needed to explore the therapeutic role of mycophenolate mofetil through alternative strategies or identify more effective interventions for osteosarcoma.