In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 8530-8530
Abstract:
8530 Background: A CTEP-sponsored phase II trial was performed to evaluate safety and clinical activity of combination therapy with CCI-779 (temsirolimus) and bevacizumab in patients with advanced melanoma. Correlative studies assessed mTOR signaling in tumor biopsies and evidence of induced immunologic dysfunction systemically. Methods: 17 patients with stage III or IV melanoma were enrolled and treated with temsirolimus (25 mg IV weekly) and bevacizumab (10 mg/kg IV every 14d, starting d.8) for up to 13 months. Clinical response was determined by RECIST criteria. Adverse events were assessed (CTCAE v3.0). Blood was collected d.1, 2, and 23 (to assess immune function), and tumor biopsies were obtained (to assess protein kinase activity and melanoma cell proliferation). Results: Treatment-related grade 3 or 4 adverse events occurred in 5 and 1 patients, respectively; 1 patient developed reversible leukoencephalopathy. In 16 patients evaluable for clinical response, best overall response was a partial response (PR) in 3 patients (19%), stable disease at 8 weeks (SD) in 9 patients (56%), and progressive disease in 4 patients. Thus, disease control rate (DCR = PR + SD) was 75%. Ten of the patients had BRAF wild-type (BRAF wt ) melanomas: these accounted for the 3 PRs (30%), and a DCR of 100%. Maximal response duration has exceeded 3 years for a BRAF wt patient. mTOR signaling was inhibited in melanoma metastases, based on decreased phospho-S6 kinase after 24h temsirolimus. Ki67 + melanoma cells in tumor biopsies decreased significantly by day 23 (p = 0.007, F-test), most notably in clinical responders. There was no significant alteration of T cell and NK function with combination treatment, by ELIspot and cytotoxicity assays. Conclusions: Combination therapy with temsirolimus and bevacizumab is well-tolerated in patients with advanced melanoma and has intriguing clinical activity. The most notable responses were in patients with BRAF wt tumors, a population with no accepted effective targeted therapy. Decreases in Ki67 + melanoma cells may be associated with clinical response. The lack of immunologic dysfunction supports future combination with immune therapies.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.8530
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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