Major efficacy of trabectedin in 2 metastatic osteosarcoma patients with wild-type Asp1104 ERCC5 tumor status

Treatment of osteosarcoma of the extremities consists of surgical resection preceded and followed by chemotherapy, including high-dose methotrexate or adriamycin-based protocols. When distant relapse occurs, therapeutic options are scarce. Trabectedin, a DNA-binding agent, is indicated for the treatment of patients with advanced soft tissue sarcomas after failure of anthracyclines and ifosfamide. In this indication, the 6-month progression-free survival is about 35-40%. Recent reports showed that some specific single nucleotide polymorphisms (SNPs) from DNA repair genes could be associated with sensitivity to trabectedin in soft tissue sarcomas.

We report our experience of 2 metastatic, heavily pre-treated osteosarcoma patients who were treated with trabectedin. Pyrosequencing analyses of tumors from both patients for several SNPs of the ERCC1, ERCC5 and BRAC1 genes were performed. Both patients showed major response to trabectedin, which was interestingly related with homozygoty of the common guanine allele of ERCC5 (G/G genotype; Asp/Asp) after pyrosenquencing analysis of tumors from both patients. This polymorphism was previously shown to be associated with better outcome in soft tissue sarcoma patients treated with trabectedin.

Homozygoty for the wild-type Asp1104 SNP of the ERCC5 gene was found in 2 cases of relapsed osteosarcoma, who responded to trabectedin.