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Published on: February 12, 2017
Results of a Randomized, Double-Blinded, Placebo-Controlled, Phase 2.5 Study of Saracatinib (AZD0530), in Patients
Kristin Baird1, John Glod2, Seth M Steinberg3
1Center for Cancer Research, NCI, NIH, Building 10 CRC, Room 1W-3750, MSC 110410 Center Drive, Bethesda, MD 20892-1104, USA.
Purpose:
Osteosarcoma is a rare cancer and a third of patients who have completed primary treatment will develop osteosarcoma recurrence. The Src pathway has been implicated in the metastatic behavior of osteosarcoma; about 95% of samples examined express Src or have evidence of downstream activation of this pathway. Saracatinib (AZD0530) is a potent and selective Src kinase inhibitor that was evaluated in adults in Phase 1 studies. The primary goal of this study was to determine if treatment with saracatinib could increase progression-free survival (PFS) for patients who have undergone complete resection of osteosarcoma lung metastases in a double-blinded, placebo-controlled trial. Patients and Methods. Subjects with recurrent osteosarcoma localized to lung and who had complete surgical removal of all lung nodules were randomized within six weeks after complete surgical resection. Saracatinib, or placebo, was administered at a dose of 175 mg orally, once daily, for up to thirteen 28-day cycles.
Results:
Thirty-seven subjects were included in the analyses; 18 subjects were randomized to receive saracatinib and 19 to receive placebo. Intent-to-treat analysis demonstrated a median PFS of 19.4 months in the saracatinib treatment group and 8.6 months in the placebo treatment group (p=0.47). Median OS was not reached in either arm.
Conclusions:
Although saracatinib was well tolerated in this patient population, there was no apparent impact of the drug in this double-blinded, placebo-controlled trial on OS, and Src inhibition alone may not be sufficient to suppress metastatic progression in osteosarcoma. There is a suggestion of potential clinical benefit as evidenced by longer PFS in patients randomized to saracatinib based on limited numbers of patients treated.
Insights
Saracatinib did not significantly improve overall survival in osteosarcoma patients after lung metastasis resection. However, the drug showed a trend toward longer progression-free survival, suggesting potential benefit in this rare cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Cancer Metastasis
Background:
- Osteosarcoma recurrence affects a third of patients post-treatment.
- The Src pathway is crucial in osteosarcoma's metastatic behavior, with 95% of samples showing Src activation.
- Saracatinib is a selective Src kinase inhibitor previously studied in adults.
Purpose of the Study:
- To evaluate if saracatinib improves progression-free survival (PFS) in patients with resected osteosarcoma lung metastases.
- To assess the efficacy of saracatinib versus placebo in a double-blinded, controlled trial.
Main Methods:
- A double-blinded, placebo-controlled trial involving 37 patients with resected osteosarcoma lung metastases.
- Patients received either 175 mg of saracatinib or a placebo orally once daily for up to 13 cycles.
Main Results:
- Median PFS was 19.4 months with saracatinib versus 8.6 months with placebo (p=0.47).
- Overall survival (OS) was not reached in either treatment group.
- Saracatinib was well-tolerated by patients.
Conclusions:
- Saracatinib did not demonstrate a significant impact on overall survival in this study.
- Src inhibition alone may be insufficient to halt metastatic osteosarcoma progression.
- A potential clinical benefit is suggested by longer PFS in the saracatinib group, warranting further investigation.
