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अमूर्त

Current Treatments for Advanced or Metastatic Osteosarcoma: Indirect Comparisons Based on Individual Patient Data Reconstructed Retrospectively from 5 Trials

Andrea Messori

Well-established regimens of standard chemotherapy are considered the standard of care for patients with advanced or metastatic osteosarcoma, but results are generally disappointing. In the past few years, however, novel treatments have been tested in clinical trials and deserve to be comparatively evaluated. Our objective was to review the current data of effectiveness for these new agents based on the end-point of Overall Survival (OS). The Shiny technique was employed for reconstructing individual patient data. A standard Cox statistics was run to estimate the Hazard Ratios (HRs) for pairwise comparisons.

After a standard literature search, four new treatments were identified (regorafenib, cabozantinib, apatinib plus camrelizumab, pembrolizumab). Evidence on effectiveness for these treatments was available from 5 phase-II clinical trials; Kaplan-Meier curves of OS were available for all treatments except pembrolizumab. Total numbers of evaluable patients were 26, 22, 42, and 43 for regorafenib, cabozantinib, apatinib plus camrelizumab, pembrolizumab, respectively. Pembrolizumab could not be evaluated owing to the lack of OS curve. Gemcitabine plus sirolimus (for a total of 35 patients) was considered the control treatment in terms of standard chemotherapy.

Using gemcitabine plus sirolimus as common comparator, each of the three novel treatments (regorafenib, cabozantinib, apatinib plus camrelizumab) showed no significant improvement in OS. The only statistical trend (at p=0.06) was found for regorafenib that showed a numerical improvement in OS compared with controls.

Our analysis indicates that these novel treatments for osteosarcoma, which share a similar efficacy with one another, provide no significant improvement in OS compared with standard chemotherapy. Further research is needed to identify other agents determining a more substantial OS improvement.