Mehmet Cem Fidan, Fatma Keskin Uzundere, Sedat Biter, Ayşe Durnalı, Ender Kalacı, Hülya Odabaşı Bükün, Erkam Kocaaslan, Emine Bihter Eniseler, Bekir Mert Durukan, Salih Tünbekici, Esra Özen Engin, Gizem Bakır Kahveci, Gamze Emin, Elif Şahin, Erdem Kölemen, Azer Gökmen, Ferit Aslan, Teoman Şakalar, Yasemin Kemal, Zuhat Urakçı, İsmail Oğuz Kara, Saadettin Kılıçkap, Ahmet Bilgehan Şahin, Selver Işık, Atike Pınar Erdoğan, Serkan Akın, Erdem Göker, İlhan Hacıbekiroğlu, Ahmet Küçükarda, Nebi Serkan Demirci, Özkan Alan
In this real-world cohort, although TKIs were associated with limited survival outcomes, they had an acceptable safety profile in patients with advanced bone sarcomas. These findings are consistent with the results of phase II studies and suggest that TKIs may be a treatment option for patients who have disease progression after standard therapies.
PURPOSE: Primary bone sarcomas, including osteosarcoma, chondrosarcoma, and Ewing sarcoma, have poor prognoses, with 5-year overall survival (OS) rates of < 20%-30% in metastatic or recurrent disease. Although tyrosine kinase inhibitors (TKIs) targeting angiogenic and oncogenic pathways have shown efficacy in phase II trials, there is a lack of supporting real-world data. This study aimed to evaluate the efficacy and safety of TKI use in patients with advanced bone sarcomas in a real-world setting.
MATERIALS AND METHODS: This multicenter, retrospective study included 72 patients with advanced or metastatic osteosarcoma, chondrosarcoma, or Ewing sarcoma who received at least one TKI (regorafenib, pazopanib, sorafenib, or cabozantinib) at multiple centers in Türkiye. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method. Adverse events were recorded and graded according to standard criteria.
RESULTS: The median age was 28.5 years (range, 17-72 years), and 62.5% (n = 45) of the patients were male. The most frequently used TKIs were regorafenib (n = 31, 43.1%) and pazopanib (n = 22, 30.6%); in the majority of patients (n = 68, 94.4%), TKIs were used as second-line or subsequent treatment. The median PFS for the entire cohort was 4.8 months (95% CI, 3.05 to 6.48), and the median OS was 9.9 months (95% CI, 6.48 to 13.25). In histologic subgroup analyses, the median PFS was 4.4 months for osteosarcoma, 4.8 months for chondrosarcoma, and 5.4 months for Ewing sarcoma. Adverse events were observed in 50% (n = 36) of patients, and 89.2% (n = 58) of these were grade 1-2. Dose reduction was required in 27.8% (n = 20) of patients, and permanent treatment discontinuation due to toxicity was necessary in 6.9% (n = 5) of patients.
CONCLUSION: In this real-world cohort, although TKIs were associated with limited survival outcomes, they had an acceptable safety profile in patients with advanced bone sarcomas. These findings are consistent with the results of phase II studies and suggest that TKIs may be a treatment option for patients who have disease progression after standard therapies.