Targeted Therapy

In a trial of 711 adult patients who achieved a response or stable disease after chemotherapy, patients were randomly assigned to receive ridaforolimus (a rapamycin inhibitor) or placebo.[49]

In a trial of 711 adult patients who achieved a response or stable disease after chemotherapy, patients were randomly assigned to receive ridaforolimus (a rapamycin inhibitor) or placebo.[49]

The administration of ridaforolimus was associated with a 3-week improvement in progression-free survival (PFS) when compared with placebo.

In another trial of 371 randomly assigned adult patients with metastatic soft tissue sarcoma that progressed after chemotherapy, pazopanib (a multitargeted receptor tyrosine kinase inhibitor) was compared with placebo.[50]

In another trial of 371 randomly assigned adult patients with metastatic soft tissue sarcoma that progressed after chemotherapy, pazopanib (a multitargeted receptor tyrosine kinase inhibitor) was compared with placebo.[50]

The median PFS for the pazopanib arm was 4.6 months, compared with 1.6 months for the placebo arm. OS was not different between the two arms.

In a study of 182 previously treated adult patients with recurrent liposarcoma, leiomyosarcoma, synovial sarcoma, and other sarcomas, patients were randomly assigned to receive either regorafenib or placebo.[51]

In a study of 182 previously treated adult patients with recurrent liposarcoma, leiomyosarcoma, synovial sarcoma, and other sarcomas, patients were randomly assigned to receive either regorafenib or placebo.[51]

Patients with nonadipocytic tumors who were treated with regorafenib had significant improvements in PFS when compared with patients who were treated with placebo.

The COG and NRG Oncology cancer consortia conducted a randomized trial of pazopanib added to neoadjuvant chemotherapy (doxorubicin and ifosfamide) and preoperative radiation therapy in pediatric (older than 2 years) and adult patients with NRSTS. Patients with intermediate- or high-grade disease whose tumors were larger than 5 cm were eligible. The end point of the trial was pathological tumor response after adjuvant therapy. Study entry was closed early because the planned interim analysis showed that the pathological response boundary was crossed. Eighty-one patients were enrolled, but only 42 (52%) were available for response data (17 patients from each group discontinued therapy for either progression, unacceptable toxicity, or patient or physician choice).[52,53]

The COG and NRG Oncology cancer consortia conducted a randomized trial of pazopanib added to neoadjuvant chemotherapy (doxorubicin and ifosfamide) and preoperative radiation therapy in pediatric (older than 2 years) and adult patients with NRSTS. Patients with intermediate- or high-grade disease whose tumors were larger than 5 cm were eligible. The end point of the trial was pathological tumor response after adjuvant therapy. Study entry was closed early because the planned interim analysis showed that the pathological response boundary was crossed. Eighty-one patients were enrolled, but only 42 (52%) were available for response data (17 patients from each group discontinued therapy for either progression, unacceptable toxicity, or patient or physician choice).[52,53]

Four of 18 patients (22%) in the control group had greater than 90% necrosis at resection, compared with 14 of 24 patients (58%) in the group treated with pazopanib, meeting the criteria for early stopping of the study.

The COG and NRG Oncology cancer consortia conducted a randomized trial of pazopanib added to neoadjuvant chemotherapy (doxorubicin and ifosfamide) and preoperative radiation therapy in pediatric (older than 2 years) and adult patients with NRSTS. Patients with intermediate- or high-grade disease whose tumors were larger than 5 cm were eligible. The end point of the trial was pathological tumor response after adjuvant therapy. Study entry was closed early because the planned interim analysis showed that the pathological response boundary was crossed. Eighty-one patients were enrolled, but only 42 (52%) were available for response data (17 patients from each group discontinued therapy for either progression, unacceptable toxicity, or patient or physician choice).[52,53]

Toxicity was greater in the pazopanib group, mainly resulting from increased myelosuppression. Wound complications were also more frequent in the pazopanib group.

The COG and NRG Oncology cancer consortia conducted a randomized trial of pazopanib added to neoadjuvant chemotherapy (doxorubicin and ifosfamide) and preoperative radiation therapy in pediatric (older than 2 years) and adult patients with NRSTS. Patients with intermediate- or high-grade disease whose tumors were larger than 5 cm were eligible. The end point of the trial was pathological tumor response after adjuvant therapy. Study entry was closed early because the planned interim analysis showed that the pathological response boundary was crossed. Eighty-one patients were enrolled, but only 42 (52%) were available for response data (17 patients from each group discontinued therapy for either progression, unacceptable toxicity, or patient or physician choice).[52,53]

With longer follow-up, the investigators were able to analyze the secondary objectives of OS and EFS.[54] At a median follow-up of 3.3 years (range, 0.1–5.8 years), the 3-year EFS rate for all patients in the intent-to-treat analysis was 52.5% for patients who received pazopanib and 50.6% for those who did not (log-rank P = .8677). The 3-year OS rate was 75.7% for patients who received pazopanib and 65.4% for the control group (log-rank P = .1919). However, the study was not powered to evaluate these end points.