Successive Osteosarcoma Relapses after the First Line O2006/Sarcome-09 Trial: What Can We Learn for Further Phase-II Trials?

SIMPLE SUMMARY: Osteosarcoma is the most common primary malignant bone tumour in adolescents and young adults. The survival of osteosarcoma patients has not improved for four decades. The purpose was to describe first and subsequent relapses in patients from the OS2006/Sarcome-09 trial, to help future trial design. Among the 434 patients with a confirmed osteosarcoma who achieved CR1 during first line treatment, 157 patients experienced at least one relapse. The 3-year progression-free and overall survival rates were 21% and 37%, respectively. Only a quarter of the patients were included in clinical trials at first recurrence. We want to promote randomised phase-II trials in osteosarcoma relapses, with broad inclusion criteria at study entry in terms of age and disease status, and PFS as primary endpoint. Surgery/local treatment of all residual lesions should be allowed when feasible. Single-arm trial design could be used for subsequent relapses. ABSTRACT: The purpose was to describe first and subsequent relapses in patients from the OS2006/Sarcome-09 trial, to help future trial design. We prospectively collected and analysed relapse data of all French patients included in the OS2006/Sarcome-09 trial, who had achieved a first complete remission. 157 patients experienced a first relapse. The median interval from diagnosis to relapse was 1.7 year (range 0.5–7.6). The first relapse was metastatic in 83% of patients, and disease was not measurable according to RECIST 1.1 criteria in 23%. Treatment consisted in systemic therapy (74%) and surgical resection (68%). A quarter of the patients were accrued in a phase-II clinical trial. A second complete remission was obtained for 79 patients. Most of them had undergone surgery (76/79). The 3-year progression-free and overall survival rates were 21% and 37%, respectively. In patients who achieved CR2, the 3y-PFS and OS rates were 39% and 62% respectively. Individual correlation between subsequent PFS durations was poor. For osteosarcoma relapses, we recommend randomised phase-II trials, open to patients from all age categories (children, adolescents, adults), not limited to patients with measurable disease (but stratified according to disease status), with PFS as primary endpoint, response rate and surgical CR as secondary endpoints.