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.