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Modest effect lenvatinib in relapsed osteosarcoma

In children and young adults with recurrent osteosarcoma, the addition of the drug lenvatinib to chemotherapy appeared to suppress tumor growth slightly longer. This was shown in an international study in which the Princess Máxima Center participated as well. (Gaspar et al., 2024)

Osteosarcoma is the most common form of bone cancer in children and adolescents, occurring most often between the ages of 10 and 19. Unfortunately, the disease often returns after treatment. In that case, treatment with chemotherapy (ifosfamide and etoposide; IE) usually follows.

The purpose of this study was to see if adding lenvatinib to IE chemotherapy improves outcomes. Lenvatinib is a so-called tyrosine kinase inhibitor (TKI). Evidence suggests that a combination of a TKI with chemotherapy could work well in recurrent osteosarcoma.


International study

Between March 2020 and November 2021, 81 children and young adults (2-25 years old) entered the study. All had relapsed or refractory osteosarcoma, that is, the disease had returned or failed to respond to previous treatment. Half of the study participants received the standard treatment with chemotherapy (IE); the other half received lenvatinib in addition to chemotherapy.

The study was conducted in 18 different countries in Europe, Asia and the Pacific, and North America. From the Princess Máxima Center, two children participated.


Small difference

In the group that received lenvatinib and chemotherapy, the tumor took slightly longer to start growing again: an average of 6.5 months compared to an average of 5.5 months in those who received chemotherapy alone. But this small difference was not statistically significant, so the possibility of coincidence cannot be ruled out. Children who had not previously been treated with ifosfamide, or who had received only one previous treatment, appeared to benefit from lenvatinib slightly more. However, these subgroups were too small for any conclusions to be drawn.

In both groups, most study participants experienced side effects, such as decreased thyroid function, anemia and nausea. These side effects were the same as was previously seen with IE chemotherapy and lenvatinib.


Valuable information

This is one of the few international studies in children and young adults with recurrent osteosarcoma. International cooperation is important to allow for sufficient numbers of children to participate in a study. The study provided valuable information for clinical practice and future study design. Future research should look at even larger groups of patients to further determine the role of TKIs in the treatment of relapsed osteosarcoma.


The scientific publication can be found here: Gaspar N, Hung GY, Strauss SJ, Campbell-Hewson Q, Dela Cruz FS, Glade Bender JL, Koh KN, Whittle SB, Chan GC, Gerber NU, Palmu S, Morgenstern DA, Longhi A, Baecklund F, Lee JA, Locatelli F, Márquez Vega C, Janeway KA, McCowage G, McCabe MG, Bidadi B, Huang J, McKenzie J, Okpara CE, Bautista F; OLIE Study Investigators. Lenvatinib Plus Ifosfamide and Etoposide in Children and Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2024 Oct 17:e244381.