Targeted therapy

A phase I/II trial of larotrectinib was completed in patients with recurrent infantile fibrosarcoma who harbored an NTRK gene fusion.[95]

A phase I/II trial of larotrectinib was completed in patients with recurrent infantile fibrosarcoma who harbored an NTRK gene fusion.[95]

Durable objective responses were seen in all eight patients, and responses occurred at a median of 1.7 months.

A phase I/II trial of larotrectinib was completed in patients with recurrent infantile fibrosarcoma who harbored an NTRK gene fusion.[95]

Most toxicities were grades 1 and 2, which included transaminitis, leukopenia, neutropenia, and vomiting. There were no grade 4 or grade 5 events attributed to larotrectinib.

In another study, three of five patients who achieved a partial response after neoadjuvant larotrectinib underwent a complete surgical resection with negative margins.[96,97]; [98][Level of evidence C2]

In another study, three of five patients who achieved a partial response after neoadjuvant larotrectinib underwent a complete surgical resection with negative margins.[96,97]; [98][Level of evidence C2]

These three patients achieved an excellent pathological response (>98% treatment effect) and remained disease free 7 to 15 months after surgery.

In a follow-up report, 159 patients with TRK fusion–positive tumors were enrolled in three phase I/II trials. There were 28 patients with infantile fibrosarcoma who were treated with single-agent larotrectinib.[99][Level of evidence C2]

In a follow-up report, 159 patients with TRK fusion–positive tumors were enrolled in three phase I/II trials. There were 28 patients with infantile fibrosarcoma who were treated with single-agent larotrectinib.[99][Level of evidence C2]

The response rate was 96%.

The Children’s Oncology Group conducted a phase II histology-agnostic trial of larotrectinib in children with NTRK fusion–positive solid tumors.[100] The study enrolled 33 patients, 18 with infantile fibrosarcoma and 15 with other solid tumors.

The Children’s Oncology Group conducted a phase II histology-agnostic trial of larotrectinib in children with NTRK fusion–positive solid tumors.[100] The study enrolled 33 patients, 18 with infantile fibrosarcoma and 15 with other solid tumors.

The overall response rate within six cycles was 94% (17 of 18; 95% adjusted CI, 72.7%–98.6%) for children with infantile fibrosarcoma and 60% (9 of 15; 95% CI, 32.3%–83.7%) for children with other solid tumors.

The Children’s Oncology Group conducted a phase II histology-agnostic trial of larotrectinib in children with NTRK fusion–positive solid tumors.[100] The study enrolled 33 patients, 18 with infantile fibrosarcoma and 15 with other solid tumors.

Six percent (2 of 33; 95% CI, 0.7%–22.2%) of patients developed progressive disease while on therapy.

The Children’s Oncology Group conducted a phase II histology-agnostic trial of larotrectinib in children with NTRK fusion–positive solid tumors.[100] The study enrolled 33 patients, 18 with infantile fibrosarcoma and 15 with other solid tumors.

The 2-year EFS and OS rates among these groups were 82.2% (95% CI, 54.3%–93.9%) and 93.8% (95% CI, 63.2%–99.1%) for infantile fibrosarcoma and 80% (95% CI, 50.0%–93.1%) and 93.3% (95% CI, 61.3%–99.0%) for other solid tumors, respectively.

The Children’s Oncology Group conducted a phase II histology-agnostic trial of larotrectinib in children with NTRK fusion–positive solid tumors.[100] The study enrolled 33 patients, 18 with infantile fibrosarcoma and 15 with other solid tumors.

Patients who underwent surgical resection of their tumor had prolonged EFS, with only 1 of these 16 patients experiencing disease progression.

LOXO-195: In a clinical trial, 1 of 8 pediatric patients with an ETV6::NTRK3–rearranged infantile fibrosarcoma developed progressive disease after 8 months of larotrectinib therapy and was found to have an acquired G623R resistance variant. The patient was treated with LOXO-195, a selective TRK inhibitor designed to overcome acquired resistance mediated by recurrent kinase domain variants. The patient experienced a transient partial response.[101] LOXO-195 is no longer being developed.

Pazopanib: A patient aged 2 months with infantile fibrosarcoma was initially treated with chemotherapy. At disease progression, a response was seen with pazopanib therapy.[102]