Phase 3 NIH Study Suggests Sorafenib Improves Survival in Rare Sarcomas

Results from a trial sponsored by the National Cancer Institute (NCI), a part of the National Institutes of Health (NIH), demonstrate that sorafenib tosylate (Nexavar) extended progression-free survival (PFS) in patients with desmoid tumors or aggressive fibromatosis (DT/DF) when compared to placebo.

Administered in pill form, the targeted treatment has been developed to interfere with the growth of cancer cells and new blood vessels.

The trial was designed and conducted by researchers with the Alliance for Clinical Trials in Oncology and the drug was provided by Bayer HealthCare AG, the study’s primary sponsor. Based on interim results, the data and safety monitoring board overseeing the trial recommended that primary data from the study be released.

The Phase 3 double-blind A091105 clinical trial enrolled 87 patients with DT/DF between March 2014 and December 2016. Patients — all of whom had disease that could not be surgically removed, that had grown, or that was causing symptoms and met specific criteria – were randomly assigned to one of 2 treatment arms. Participants in the first treatment arm received sorafenib (400 mg/day), while patients in the second received a matched placebo.

The trial was designed to target an improvement in median PFS from 6 months for placebo to 15 months for sorafenib. Based on an interim analysis of the first 75 patients enrolled, the demonstrated improvement in PFS was exceeded.

“Sorafenib is a novel way of treating this rare cancer,” said lead investigator and study chair Mrinal M. Gounder, M.D., sarcoma medical oncologist at Memorial Sloan Kettering Cancer Center in New York City in a press release. “The promising results of this phase 3 trial represent a paradigm shift in the approach to treatment of patients with desmoid tumors.”

Patients in both groups continued treatment until their tumors grew or they experienced drug-related adverse events (AEs). Patients who were administered placebo were informed of their assignment in the event of tumor progression and were permitted to receive sorafenib. Patients who received sorafenib were more likely to experience drug-related AEs, but side effects were generally not severe.

While sorafenib is currently approved for the treatment of some patients with advanced kidney, liver, and thyroid cancer, there is no standard of care for patients with these rare tumors. Jeff Abrams, M.D., clinical director of NCI’s Division of Cancer Treatment and Diagnosis explains: “The effectiveness of the treatments that are used for (DT/DF)—for example, surgery, radiation, and chemotherapy—is generally limited, but the interim results of this trial are promising and may offer a new treatment alternative.”

DT/DF are rare sarcomas that occur in an estimated 1,000 Americans each year, most of whom are pediatric patients. They typically develop in the extremities or abdomen, are locally aggressive, and can result in debilitating pain and limited mobility. They can spread to vital organs or structures, leading to bowel obstructions and other severe complications.

“We welcome the potentially practice-changing results from this NCI-sponsored trial in patients with desmoid tumors or aggressive fibromatosis and are looking forward to the full data presentation at an upcoming scientific congress,” said Svetlana Kobina, M.D., Ph.D., head of Global Medical Affairs, Oncology, at Bayer.

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