Lenvima Combo Misses End Goal in Children with Osteosarcoma

December 5, 2024
Spencer Feldman

Combination therapy of Lenvima with Ipex and Vepesid misses end goal in children with osteosarcoma, but further research is needed.

Among children and young adults with relapsed or refractory osteosarcoma, the combination of Lenvima (lenvatinib) to Ipex (ifosfamide) and Vepesid (etoposide) did not meet its goal of prespecified statistical significance for improved progression-free survival (PFS) versus Ipex and Vepesid (IE) alone.

After a median follow-up of 12.2 months, the median PFS was 6.5 months for the Lenvima plus IE (LEN-IE) group and 5.5 months for the IE group. The four-month PFS rate was 76.3% in the LEN-IE group and 66% in the IE group. The progression-free survival difference between the two arms was found by researchers to be statistically significant.

According to study findings published in JAMA Oncology, “[This] data suggest that patients with relapsed or refractory osteosarcoma may benefit from earlier LEN-IE treatment; however, subgroup analyses were exploratory and limited by small sample sized and should be interpreted with caution,” study authors wrote.

In addition, the median overall survival was 11.9 months in the LEN-IE group and 17.4 months in the IE group; however, a greater proportion of patients in the IE arm underwent surgery or received subsequent anticancer therapy and crossed over from the IE arm which made overall survival difficult to measure, according to the study.

“For both arms, median [overall survival] was longer in patients who underwent surgery than in those who did not. These results suggest that surgical resection was associated with prolonged survival, consistent with published data,” study authors wrote.

In each treatment group, 38 patients experienced treatment-related side effects. Among those received LEN-IE, 31 patients experienced similar side effects, while 35 patients who received IE alone reported grade 3 (severe) or worse side effects. Serious treatment-related side effects occurred in 23 patients in the LEN-IE group and 12 patients in the IE group.

The most common treatment-related side effects, occurring in 40% or more of patients, in the LEN-IE group were hypothyroidism (32 patients), anemia (25 patients), decreased platelet count (20 patients), proteinuria (20 patients) and nausea (19 patients). In the IE group, anemia (23 patients) and decreased platelet count (16 patients) were the most common. Treatment-related pneumothorax occurred in seven patients in the LEN-IE group and none in the IE group. Pneumothorax, regardless of relatedness, occurred in 11 patients and one patient, respectively.

“The overall safety profile of LEN-IE in OLIE was consistent with known safety profiles of the individual agents and the safety profile previously observed for LEN-IE in relapsed or refractory osteosarcoma in pediatric and young adult patients, with no new safety signals detected,” study authors wrote.

A total of 81 patients with a median age of 15 years were included in the study. The median duration of treatment was 7.6 months in the LEN-IE group and 2.8 months in the IE group.

Patients were to receive Lenvima at a dose of 14 milligrams per square meter (mg/m2) taken orally once daily. This was then combined with up to five cycles of Ipex at a dose of 3,000 mg/m2, administered intravenously, along with Vepesid at a dose of 100 mg/m2, also given intravenously on days one to three of each cycle. This treatment protocol was compared to IE alone at the same doses.

The primary focus of this trial was PFS and secondary focuses which included PFS rate at four months and overall survival.

Reference:

“Lenvatinib Plus Ifosfamide and Etoposide in Children and Young Adults With Relapsed Osteosarcoma” by Dr. Nathalie Gasper, et al., JAMA Oncology.

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