Supplementary Text. from Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/Mel47)

Slingluff, Craig L.; Petroni, Gina R.; Molhoek, Kerrington R.; Brautigan, David L.; Chianese-Bullock, Kimberly A.; Shada, Amber L.; Smolkin, Mark E.; Olson, Walter C.; Gaucher, Alison; Chase, Cheryl Murphy; Grosh, William W.; Weiss, Geoffrey R.; Wagenseller, Aubrey G.; Olszanski, Anthony J.; Martin, Lainie; Shea, Sofia M.; Erdag, Gulsun; Ram, Prahlad; Gershenwald, Jeffrey E.; Weber, Michael J.

doi:10.1158/1078-0432.22452708.v1

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Supplementary Text. from Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/Mel47)

journal contribution

posted on 2023-03-31, 17:55 authored by Craig L. Slingluff, Gina R. Petroni, Kerrington R. Molhoek, David L. Brautigan, Kimberly A. Chianese-Bullock, Amber L. Shada, Mark E. Smolkin, Walter C. Olson, Alison Gaucher, Cheryl Murphy Chase, William W. Grosh, Geoffrey R. Weiss, Aubrey G. Wagenseller, Anthony J. Olszanski, Lainie Martin, Sofia M. Shea, Gulsun Erdag, Prahlad Ram, Jeffrey E. Gershenwald, Michael J. Weber

Supplemental text for Methods and Results.

History

ARTICLE ABSTRACT

Purpose: A CTEP-sponsored phase II trial was conducted to evaluate safety and clinical activity of combination therapy with CCI-779 (temsirolimus) and bevacizumab in patients with advanced melanoma.Experimental Design: Patients with unresectable stage III to IV melanoma were treated intravenously with temsirolimus 25 mg weekly and bevacizumab 10 mg every 2 weeks. Adverse events were recorded using CTCAE v3.0. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors and overall survival was recorded. Correlative studies measured protein kinases and histology of tumor biopsies and immune function in peripheral blood.Results: Seventeen patients were treated. Most patients tolerated treatment well, but 2 had grade 4 lymphopenia and 1 developed reversible grade 2 leukoencephalopathy. Best clinical response was partial response (PR) in 3 patients [17.7%, 90% confidence interval (CI) 5, 0–39.6], stable disease at 8 weeks (SD) in 9 patients, progressive disease (PD) in 4 patients, and not evaluable in 1 patient. Maximal response duration for PR was 35 months. Ten evaluable patients had BRAFWT tumors, among whom 3 had PRs, 5 had SD, and 2 had PD. Correlative studies of tumor biopsies revealed decreased phospho-S6K (d2 and d23 vs. d1, P < 0.001), and decreased mitotic rate (Ki67+) among melanoma cells by d23 (P = 0.007). Effects on immune functions were mixed, with decreased alloreactive T-cell responses and decreased circulating CD4+FoxP3+ cells.Conclusion: These data provide preliminary evidence for clinical activity of combination therapy with temsirolimus and bevacizumab, which may be greater in patients with BRAFwt melanoma. Mixed effects on immunologic function also support combination with immune therapies. Clin Cancer Res; 19(13); 3611–20. ©2013 AACR.