Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America

Walter M. Stadler, Robert A. Figlin, David F. McDermott, Janice P. Dutcher, Jennifer J. Knox, Wilson H. Miller, John D. Hainsworth, Charles A. Henderson, Jeffrey R. George, Julio Hajdenberg, Tamila L. Kindwall-Keller, Marc S. Ernstoff, Harry A. Drabkin, Brendan D. Curti, Luis Chu, Christopher Ryan, Sebastien J. Hotte, Chenghua Xia, Lisa Cupit, Ronald M. Bukowski

    Research output: Contribution to journalArticle

    205 Citations (Scopus)

    Abstract

    BACKGROUND: The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) program made sorafenib available to patients with advanced renal cell carcinoma (RCC) before regulatory approval. METHODS: In this nonrandomized, open-label expanded access program, 2504 patients from the United States and Canada were treated with oral sorafenib 400 mg twice daily. Safety and efficacy were explored overall and in subgroups of patients including those with no prior therapy, nonclear cell (nonclear cell) RCC, brain metastases, prior bevacizumab treatment, and elderly patients. Sorafenib was approved for RCC 6 months after study initiation, at which time patients with no prior therapy or with nonclear cell RCC could enroll in an extension protocol for continued assessment for a period of 6 months. RESULTS: The most common grade ≥2 drug-related adverse events were hand-foot skin reaction (18%), rash (14%), hypertension (12%), and fatigue (11%). In the 1891 patients evaluable for response, complete response was observed in 1 patient, partial response in 67 patients (4%), and stable disease for at least 8 weeks in 1511 patients (80%). Median progression-free survival in the extension population was 36 weeks (95% confidence interval [CI], 33-45 weeks; censorship rate, 56%); median overall survival in the entire population was 50 weeks (95% CI, 46-52 weeks; censorship rate, 63%). The efficacy and safety results were similar across the subgroups. CONCLUSIONS: Sorafenib 400 mg twice daily demonstrated activity and a clinically acceptable toxicity profile in all patient subsets enrolled in the ARCCS expanded access program (clinicaltrials.gov identifier: NCT00111020).

    Original languageEnglish (US)
    Pages (from-to)1272-1280
    Number of pages9
    JournalCancer
    Volume116
    Issue number5
    DOIs
    StatePublished - Mar 1 2010

    Fingerprint

    North America
    Renal Cell Carcinoma
    Safety
    sorafenib
    Confidence Intervals
    Cell- and Tissue-Based Therapy
    Exanthema
    Drug-Related Side Effects and Adverse Reactions
    Population
    Disease-Free Survival
    Canada
    Fatigue
    Foot
    Hand
    Neoplasm Metastasis
    Hypertension
    Skin
    Survival
    Brain
    Therapeutics

    Keywords

    • Bevacizumab
    • Brain metastases
    • Expanded access program
    • First-line
    • Nonclear cell
    • Progression-free survival
    • Renal cell carcinoma
    • Sorafenib

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    Stadler, W. M., Figlin, R. A., McDermott, D. F., Dutcher, J. P., Knox, J. J., Miller, W. H., ... Bukowski, R. M. (2010). Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer, 116(5), 1272-1280. https://doi.org/10.1002/cncr.24864

    Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. / Stadler, Walter M.; Figlin, Robert A.; McDermott, David F.; Dutcher, Janice P.; Knox, Jennifer J.; Miller, Wilson H.; Hainsworth, John D.; Henderson, Charles A.; George, Jeffrey R.; Hajdenberg, Julio; Kindwall-Keller, Tamila L.; Ernstoff, Marc S.; Drabkin, Harry A.; Curti, Brendan D.; Chu, Luis; Ryan, Christopher; Hotte, Sebastien J.; Xia, Chenghua; Cupit, Lisa; Bukowski, Ronald M.

    In: Cancer, Vol. 116, No. 5, 01.03.2010, p. 1272-1280.

    Research output: Contribution to journalArticle

    Stadler, WM, Figlin, RA, McDermott, DF, Dutcher, JP, Knox, JJ, Miller, WH, Hainsworth, JD, Henderson, CA, George, JR, Hajdenberg, J, Kindwall-Keller, TL, Ernstoff, MS, Drabkin, HA, Curti, BD, Chu, L, Ryan, C, Hotte, SJ, Xia, C, Cupit, L & Bukowski, RM 2010, 'Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America', Cancer, vol. 116, no. 5, pp. 1272-1280. https://doi.org/10.1002/cncr.24864
    Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH et al. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer. 2010 Mar 1;116(5):1272-1280. https://doi.org/10.1002/cncr.24864
    Stadler, Walter M. ; Figlin, Robert A. ; McDermott, David F. ; Dutcher, Janice P. ; Knox, Jennifer J. ; Miller, Wilson H. ; Hainsworth, John D. ; Henderson, Charles A. ; George, Jeffrey R. ; Hajdenberg, Julio ; Kindwall-Keller, Tamila L. ; Ernstoff, Marc S. ; Drabkin, Harry A. ; Curti, Brendan D. ; Chu, Luis ; Ryan, Christopher ; Hotte, Sebastien J. ; Xia, Chenghua ; Cupit, Lisa ; Bukowski, Ronald M. / Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. In: Cancer. 2010 ; Vol. 116, No. 5. pp. 1272-1280.
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    abstract = "BACKGROUND: The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) program made sorafenib available to patients with advanced renal cell carcinoma (RCC) before regulatory approval. METHODS: In this nonrandomized, open-label expanded access program, 2504 patients from the United States and Canada were treated with oral sorafenib 400 mg twice daily. Safety and efficacy were explored overall and in subgroups of patients including those with no prior therapy, nonclear cell (nonclear cell) RCC, brain metastases, prior bevacizumab treatment, and elderly patients. Sorafenib was approved for RCC 6 months after study initiation, at which time patients with no prior therapy or with nonclear cell RCC could enroll in an extension protocol for continued assessment for a period of 6 months. RESULTS: The most common grade ≥2 drug-related adverse events were hand-foot skin reaction (18{\%}), rash (14{\%}), hypertension (12{\%}), and fatigue (11{\%}). In the 1891 patients evaluable for response, complete response was observed in 1 patient, partial response in 67 patients (4{\%}), and stable disease for at least 8 weeks in 1511 patients (80{\%}). Median progression-free survival in the extension population was 36 weeks (95{\%} confidence interval [CI], 33-45 weeks; censorship rate, 56{\%}); median overall survival in the entire population was 50 weeks (95{\%} CI, 46-52 weeks; censorship rate, 63{\%}). The efficacy and safety results were similar across the subgroups. CONCLUSIONS: Sorafenib 400 mg twice daily demonstrated activity and a clinically acceptable toxicity profile in all patient subsets enrolled in the ARCCS expanded access program (clinicaltrials.gov identifier: NCT00111020).",
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    T1 - Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America

    AU - Stadler, Walter M.

    AU - Figlin, Robert A.

    AU - McDermott, David F.

    AU - Dutcher, Janice P.

    AU - Knox, Jennifer J.

    AU - Miller, Wilson H.

    AU - Hainsworth, John D.

    AU - Henderson, Charles A.

    AU - George, Jeffrey R.

    AU - Hajdenberg, Julio

    AU - Kindwall-Keller, Tamila L.

    AU - Ernstoff, Marc S.

    AU - Drabkin, Harry A.

    AU - Curti, Brendan D.

    AU - Chu, Luis

    AU - Ryan, Christopher

    AU - Hotte, Sebastien J.

    AU - Xia, Chenghua

    AU - Cupit, Lisa

    AU - Bukowski, Ronald M.

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    N2 - BACKGROUND: The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) program made sorafenib available to patients with advanced renal cell carcinoma (RCC) before regulatory approval. METHODS: In this nonrandomized, open-label expanded access program, 2504 patients from the United States and Canada were treated with oral sorafenib 400 mg twice daily. Safety and efficacy were explored overall and in subgroups of patients including those with no prior therapy, nonclear cell (nonclear cell) RCC, brain metastases, prior bevacizumab treatment, and elderly patients. Sorafenib was approved for RCC 6 months after study initiation, at which time patients with no prior therapy or with nonclear cell RCC could enroll in an extension protocol for continued assessment for a period of 6 months. RESULTS: The most common grade ≥2 drug-related adverse events were hand-foot skin reaction (18%), rash (14%), hypertension (12%), and fatigue (11%). In the 1891 patients evaluable for response, complete response was observed in 1 patient, partial response in 67 patients (4%), and stable disease for at least 8 weeks in 1511 patients (80%). Median progression-free survival in the extension population was 36 weeks (95% confidence interval [CI], 33-45 weeks; censorship rate, 56%); median overall survival in the entire population was 50 weeks (95% CI, 46-52 weeks; censorship rate, 63%). The efficacy and safety results were similar across the subgroups. CONCLUSIONS: Sorafenib 400 mg twice daily demonstrated activity and a clinically acceptable toxicity profile in all patient subsets enrolled in the ARCCS expanded access program (clinicaltrials.gov identifier: NCT00111020).

    AB - BACKGROUND: The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) program made sorafenib available to patients with advanced renal cell carcinoma (RCC) before regulatory approval. METHODS: In this nonrandomized, open-label expanded access program, 2504 patients from the United States and Canada were treated with oral sorafenib 400 mg twice daily. Safety and efficacy were explored overall and in subgroups of patients including those with no prior therapy, nonclear cell (nonclear cell) RCC, brain metastases, prior bevacizumab treatment, and elderly patients. Sorafenib was approved for RCC 6 months after study initiation, at which time patients with no prior therapy or with nonclear cell RCC could enroll in an extension protocol for continued assessment for a period of 6 months. RESULTS: The most common grade ≥2 drug-related adverse events were hand-foot skin reaction (18%), rash (14%), hypertension (12%), and fatigue (11%). In the 1891 patients evaluable for response, complete response was observed in 1 patient, partial response in 67 patients (4%), and stable disease for at least 8 weeks in 1511 patients (80%). Median progression-free survival in the extension population was 36 weeks (95% confidence interval [CI], 33-45 weeks; censorship rate, 56%); median overall survival in the entire population was 50 weeks (95% CI, 46-52 weeks; censorship rate, 63%). The efficacy and safety results were similar across the subgroups. CONCLUSIONS: Sorafenib 400 mg twice daily demonstrated activity and a clinically acceptable toxicity profile in all patient subsets enrolled in the ARCCS expanded access program (clinicaltrials.gov identifier: NCT00111020).

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    KW - Sorafenib

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