Osteosarcoma (OS) is the most common bone cancer in children and young adults. It is more common in those aged 10 to 19 years. It affects about 3.4 people per million each year worldwide. This cancer comes back in 30% to 40% patients with localized disease.  It returns in 80% of those with cancer that has spread in the body. Treatment guidelines for hard-to-treat OS vary across the world. Refractory OS is when the cancer has not responded to treatment.

Abnormal signaling in certain cell receptors can cause OS cells to grow. These cells are called tyrosine kinase receptors.

Drugs called tyrosine kinase inhibitors (TKIs) could help treat cancer. But isn’t known how effective they are. 

Lenvatinib is an oral TKI cancer treatment. Lenvatinib can be given with two other drugs called  ifosfamide and etoposide. This is a treatment known as LEN-IE. LEN-IE shows better anti-tumor activity than either treatment alone. The given dose was 14 mg/m² daily.

In this study, lenvatinib alone showed some effectiveness. Combining it with drugs to treat cancer (LEN-IE) improved progression-free survival (PFS) and overall survival in patients.

This trial aimed to compare the safety and effectiveness of LEN-IE treatment, versus IE alone. This treatment was for young patients with relapsed or hard to manage OS. The trial took place in a number of regions.

Methods

Treatments

The OLIE trial tested how well and how safe lenvatinib works. Lenvatinib was given with ifosfamide and etoposide. This was to compare to treatment of ifosfamide and etoposide alone. The treatment was a daily pill and was also delivered via a vein. If patients receiving only ifosfamide and etoposide saw their disease get worse, they could switch treatment to the lenvatinib combination.

Main goals

• Primary Goal: To see how long patients live without their cancer getting worse. This is known as progression-free survival (PFS).

• Other Goals: To measure the PFS rate at 4 months and overall survival. Side effects were also recorded and studied.

The main goal was measuring how long patients lived without their cancer getting worse. Patients on the LEN-IE treatment had a median PFS of 6.5 months. Those on IE alone had 5.5 months. Patients who hadn’t had the treatment ifosfamide before shows similar results. It was also seen when patients had only one prior treatment of ifosfamide. This suggests that starting LEN-IE earlier might help. However, there were a small number of patients in the trial. It is hard to widely apply trial results when there is a small number of patients.

Overall Survival

• •Median overall survival: 11.9 months for LEN-IE and 17.4 months for IE. This study wasn’t designed to measure overall survival rates.
• • Patients who had surgery lived longer than those who didn’t. This matches other studies. The final follow-up showed similar overall survival results. It also showed that the short follow-up period might be limiting.

More males were in the LEN-IE group, which might have affected results. Males with OS generally have worse long-term outcomes than females.

This trial highlights the potential benefits and risks of the LEN-IE treatment for OS.

References:

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 Dec 1;10(12):1645-1653. doi: 10.1001/jamaoncol.2024.4381. PMID: 39418029; PMCID: PMC11581622.