Phase II Study of Sorafenib in Patients With Metastatic or Recurrent Sarcomas
From the Departments of Medicine, Pathology, Radiology, and Biostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center; Rockefeller University, New York, NY; Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI; Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago; Evanston Northwestern Health Care, Evanston, IL; Carolinas Hematology-Oncology and University of North Carolina, Charlotte, NC; Division of Hematology and Oncology, University Hospitals Case Medical Center, Case Comprehensive Cancer Center, Cleveland, OH; Institute for Drug Development, Cancer Therapy and Research Center at the University of Texas Health Science Center, San Antonio, TX; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC; and the University of Colorado Cancer Center, Aurora, CO.
Corresponding author: Robert G. Maki, MD, PhD, Melanoma-Sarcoma Program, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Howard 909, New York, NY 10065; e-mail: makir@mskcc.org.
Purpose Since activity of sorafenib was observed in sarcoma patients in a phase I study, we performed a multicenter phase II study of daily oral sorafenib in patients with recurrent or metastatic sarcoma.
Patients and Methods We employed a multiarm study design, each representing a sarcoma subtype with its own Simon optimal two-stage design. In each arm, 12 patients who received 0 to 1 prior lines of therapy were treated (0 to 3 for angiosarcoma and malignant peripheral-nerve sheath tumor). If at least one Response Evaluation Criteria in Solid Tumors (RECIST) was observed, 25 further patients with that sarcoma subtype were accrued.
Results Between October 2005 and November 2007, 145 patients were treated; 144 were eligible for toxicity and 122 for response. Median age was 55 years; female-male ratio was 1.8:1. The median number of cycles was 3. Five of 37 patients with angiosarcoma had a partial response (response rate, 14%). This was the only arm to meet the RECIST response rate primary end point. Median progression-free survival was 3.2 months; median overall survival was 14.3 months. Adverse events (typically dermatological) necessitated dose reduction for 61% of patients. Statistical modeling in this limited patient cohort indicated sorafenib toxicity was correlated inversely to patient height. There was no correlation between phosphorylated extracellular signal regulated kinase expression and response in six patients with angiosarcoma with paired pre- and post-therapy biopsies.
Conclusion As a single agent, sorafenib has activity against angiosarcoma and minimal activity against other sarcomas. Further evaluation of sorafenib in these and possibly other sarcoma subtypes appears warranted, presumably in combination with cytotoxic or kinase-specific agents.
Supported by the National Cancer Institute (NCI) Program Project Grant No. CA47179, NCI phase II contract CM62202, Cycle for Survival, the Shuman Family Fund for GIST research, and the Sarcoma Research Fund.
Presented in part in oral format at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL.Multicenter Phase II Trial of Sunitinib in the Treatment of Nongastrointestinal Stromal Tumor Sarcomas
From the Dana-Farber Cancer Institute; Massachusetts General Hospital; Ludwig Center at Dana-Farber/Harvard Cancer Center, Boston, MA; and the Memorial Sloan-Kettering Cancer Center, New York, NY.
Corresponding author: Suzanne George, MD, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, 44 Binney St, D1210, Boston, MA 02115; e-mail: suzanne_george@dfci.harvard.edu.
Purpose To evaluate the potential benefit of continuous daily dosing sunitinib in patients with advanced nongastrointestinal stromal tumor (GIST) sarcomas.
Patients and Methods A total of 53 patients with advanced non-GIST soft tissue sarcomas received sunitinib 37.5 mg daily. Primary end point was Response Evaluation Criteria in Solid Tumors defined response. Secondary end points were stable disease at 16 and 24 weeks. [18F]-fluorodeoxyglucose positron emission tomography was performed on a subset of 24 patients at baseline and after 10 to 14 days of therapy.
Results Forty-eight patients were eligible for response. One patient (desmoplastic round cell tumor [DSRCT]) achieved a confirmed partial response (PR) and remained on study for 56 weeks. Ten patients (20%) achieved stable disease for at least 16 weeks. Metabolic PR was seen in 10 (47%) of 21 of patients. Metabolic stable disease was seen in 11 (52%) of 21. There were no unexpected toxicities observed.
Conclusion Sunitinib demonstrated notable evidence of metabolic response in several patients with non-GIST sarcoma. The relevance of disease control observed in subtypes with an indolent natural history is unknown, however, the durable disease control observed in DSRCT, solitary fibrous tumor, and giant cell tumor of bone suggests that future evaluation of sunitinib in these subtypes may be warranted.
Supported in part by Pfizer Inc; the Virginia and Daniel K. Ludwig Trust for Cancer Research; Cycle for Survival and NCI program project CA47179 (R.G.M., G.K.S.) and correlative studies supported by National Comprehensive Cancer Network, protocol No. NCCN-S109.
Presented in part at the 13th Annual Connective Tissue Oncology Society Conference, Seattle, WA, October 31 to November 3, 2007; and the 44th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 30 to June 3, 2008.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Clinical Trials repository link available JCO.org.
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