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my personal edition > oncology other > news
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DGDispatch
CP-751,871 May Have Benefits in the Treatment of Ewing's Sarcoma: Presented at EORTC-NCI-AACR
By Chris Berrie
GENEVA -- October 28, 2008 -- A fully human, immunoglobulin G2 monoclonal antibody against the insulin-like growth factor-1 receptor (IGF-1R) appears to be well tolerated by patients and shows clinical benefits in patients with various sarcoma subtypes who are refractory to standard therapies, and especially in patients with Ewing's sarcoma.
Data from expansion cohorts following a dose-escalation phase 1 trial of the investigative compound -- CP-751,871 -- were reported here on October 23 at the 20th International Symposium of the European Organisation for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI), and the American Association for Cancer Research (AACR).
According to investigator Sophie Postel-Vinay, MD, Drug Development Unit, Royal Marsden Hospital, Institute of Cancer Research, Sutton, United Kingdom, IGF-1R is a receptor tyrosine kinase that regulates a variety of cellular processes, including cell growth and proliferation, and inhibition of apoptosis.
IGF-1R apparently plays a key role in the initiation and maintenance of various types of sarcomas, so the rationale for using CP-751,871 is inhibition of IGF-1R autophosphorylation, which results in the removal of IGF-1R by internalisation and degradation.
Dr. Postel-Vinay and colleagues therefore conducted their phase 1 study to evaluate the safety of CP-751,871 as well as to assess the drug's preliminary activity and pharmacokinetics.
They enrolled patients aged 18 years or more with advanced sarcoma that was relapsed or refractory to standard therapies, or for which no effective therapy exists. Among patients with Ewing's sarcoma family of tumours, patient age was expanded to include those 9 years or older. Further requirements were Eastern Cooperative Oncology Group performance status (ECOG-PS) 0 or 1 and adequate bone marrow, renal, and hepatic function.
Exclusion criteria were recent antitumour treatment or use of high-dose corticosteroids, major surgery, symptomatic or untreated brain metastases, or significant cardiac disease.
Baseline clinical characteristics of the 29 patients with sarcoma (median age, 30 years; male, 72%) included equal levels of ECOG-PS 0/1, with the following tumour types: Ewing's sarcoma (55%); synovial (17%); desmoplastic small round-cell tumours (10%); rhabdomyosarcoma (7%); fibrosarcoma (7%); and chondrosarcoma (3%). The majority of patients had received prior therapies: partial/complete resection (69%); radiotherapy (69%); and chemotherapy (97%).
Tumour response was assessed according to the Response Evaluation Criteria in Solid Tumours.
According to the Dr. Postel-Vinay, promising preliminary activity has been seen for the 24 evaluable patients. The rate of disease control was 54%, with 1 complete and 1 partial response, and 11 patients with stable disease.
After a total of 127 cycles of treatment in 26 evaluable patients, treatment-related serious adverse events included 1 grade IV increased uric acid and 1 grade III bilateral deep vein thrombosis. Grade II adverse events, which were seen in 7.7% of patients, were lymphopenia, fatigue, cramps, headache, thrush, and vomiting.
Dr. Postel-Vinay noted that the only complete response has been seen in Ewing's [sarcoma]. With a disease control rate in these patients of 31%, CP-751,871 is already being assessed in a phase 2 study for patients with Ewing's sarcoma family of tumours.
Funding for this study was provided Pfizer Global Research and Development.
[Presentation title: Safety, Pharmacokinetics and Preliminary Activity of the Anti-IGF-1R Antibody CP-751,871 in Patients With Sarcoma. Abstract 388]
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