Dr Randall on the Evaluation of Ganitumab Plus VDC/IE in Newly Diagnosed Metastatic Ewing Sarcoma

R. Lor Randall, MD, FACS, The David Linn Endowed Chair for Orthopedic Surgery, professor and chair, Department of Orthopedic Surgery, University of California Davis Health, discusses the investigation of ganitumab (AMG 479) plus standard-of-care (SOC) interval-compressed chemotherapy in a phase 3 trial (NCT02306161) for newly diagnosed metastatic Ewing sarcoma.

The randomized phase 3 trial compared interval-compressed chemotherapy, which consists of alternating vincristine, doxorubicin, and cyclophosphamide with ifosfamide and etoposide (VDC/IE) every 2 weeks, with VDC/IE plus the IGF1R antibody ganitumab in this disease setting. Patients were randomized 1:1 to either regimen. The trial was supported by previous research on ganitumab in other tumor types, which suggested that the addition of the agent to combination chemotherapy could also improve patient responses within metastatic Ewing sarcoma, Randall says.

Results from the trial were recently published in the Journal of Clinical Oncology, and showed that the addition of ganitumab to VDC/IE did not increase survival in this patient population compared with VDC/IE alone, Randall reports. Of the 150 patients treated with ganitumab plus chemotherapy, the 3-year event-free survival (EFS) rate was 39.1%, and the overall survival (OS) rate was 56.7%. Conversely, 3-year EFS and OS rates in the control arm were 37.4% and 59.5%, respectively.

Moreover, a slight increase in toxicity was seen with ganitumab plus VDC/IE, Randall continues. Specifically, ganitumab plus VDC/IE was associated with a higher incidence of pneumonitis after radiation involving thoracic fields, increased rates of febrile neutropenia, and elevated alanine transaminase levels.

Based on these negative results, further investigation of ganitumab in newly diagnosed metastatic Ewing sarcoma is not recommended, Randall states. Instead, other biologic targeted agents are being considered for future investigations in this patient population, Randall concludes.