Evan Y Yu1, Hongli Li2, Celestia S Higano2, Neeraj Agarwal2, Sumanta K Pal2, Ajjai Alva2, Elisabeth I Heath2, Elaine T Lam2, Shilpa Gupta2, Michael B Lilly2, Yoshio Inoue2, Kim N Chi2, Nicholas J Vogelzang2, David I Quinn2, Heather H Cheng2, Stephen R Plymate2, Maha Hussain2, Catherine M Tangen2, Ian M Thompson2. 1. Evan Y. Yu, Hongli Li, Celestia S. Higano, Heather H. Cheng, and Catherine M. Tangen, Fred Hutchinson Cancer Research Center, University of Washington; Stephen R. Plymate, Harborview Medical Center, University of Washington, Seattle; Yoshio Inoue, Multicare Regional Cancer Center, Tacoma, WA; Neeraj Agarwal, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Sumanta K. Pal, City of Hope, Duarte; David I. Quinn, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA; Ajjai Alva, University of Michigan, Ann Arbor; Elisabeth I. Heath, Karmanos Cancer Center, Wayne State University, Detroit, MI; Elaine T. Lam, University of Colorado, Denver, CO; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida Morisani College of Medicine, Tampa, FL; Michael B. Lilly, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC; Kim N. Chi, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada; Nicholas J. Vogelzang, Comprehensive Cancer Centers of Nevada, Las Vegas, NV; and Ian M. Thompson Jr, University of Texas Health Science Center at San Antonio, San Antonio, TX. evanyu@u.washington.edu. 2. Evan Y. Yu, Hongli Li, Celestia S. Higano, Heather H. Cheng, and Catherine M. Tangen, Fred Hutchinson Cancer Research Center, University of Washington; Stephen R. Plymate, Harborview Medical Center, University of Washington, Seattle; Yoshio Inoue, Multicare Regional Cancer Center, Tacoma, WA; Neeraj Agarwal, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Sumanta K. Pal, City of Hope, Duarte; David I. Quinn, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA; Ajjai Alva, University of Michigan, Ann Arbor; Elisabeth I. Heath, Karmanos Cancer Center, Wayne State University, Detroit, MI; Elaine T. Lam, University of Colorado, Denver, CO; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida Morisani College of Medicine, Tampa, FL; Michael B. Lilly, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC; Kim N. Chi, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada; Nicholas J. Vogelzang, Comprehensive Cancer Centers of Nevada, Las Vegas, NV; and Ian M. Thompson Jr, University of Texas Health Science Center at San Antonio, San Antonio, TX.
Abstract
PURPOSE: Cixutumumab, formerly IMC-A12, is a recombinant human monoclonal immunoglobulin G1 antibody that targets insulin-like growth factor I receptor (IGF-IR). Cixutumumab was synergistic with castration in a hormone-sensitive prostate cancer xenograft model. PATIENTS AND METHODS: Patients with new metastatic prostate cancer were randomly assigned within 30 days of initiating androgen deprivation (AD) to cixutumumab added to a luteinizing hormone-releasing hormone agonist with bicalutamide versus AD alone. With 180 patients and one-sided alpha of 0.10, there would be 90% power to detect an absolute 20% difference in undetectable prostate-specific antigen (PSA; ≤ 0.2 ng/mL) rate at 28 weeks (relative risk, 1.44); this end point was previously strongly correlated with survival. Secondary end points included the proportion of patients with PSA > 4.0 ng/mL, safety and tolerability, circulating tumor cell (CTC) levels, and seven plasma IGF-IR biomarkers. Fisher's exact test was used for the primary end point, and extended Mantel-Haenszel χ(2) test was used for three PSA response categories. RESULTS: The trial accrued 210 eligible patients (105 randomly assigned to each arm). Patient characteristics were similar in both arms. Undetectable PSA rate was 42 (40.0%) of 105 for cixutumumab plus AD and 34 (32.3%) of 105 for AD alone (relative risk, 1.24; one-sided P = .16). Lower baseline CTCs (0 v 1 to 4 v ≥ 5/7.5 mL whole blood) were associated with higher rate of PSA response (three categories; P = .036) in 39 evaluable patients. IGF-IR biomarkers were not correlated with PSA outcome, and cixutumumab did not significantly change these biomarker levels. CONCLUSION:Cixutumumab plus AD did not significantly increase the undetectable PSA rate in men with new metastatic hormone-sensitive prostate cancer. CTCs at baseline may carry prognostic value.
RCT Entities:
PURPOSE:Cixutumumab, formerly IMC-A12, is a recombinant human monoclonal immunoglobulin G1 antibody that targets insulin-like growth factor I receptor (IGF-IR). Cixutumumab was synergistic with castration in a hormone-sensitive prostate cancer xenograft model. PATIENTS AND METHODS: Patients with new metastatic prostate cancer were randomly assigned within 30 days of initiating androgen deprivation (AD) to cixutumumab added to a luteinizing hormone-releasing hormone agonist with bicalutamide versus AD alone. With 180 patients and one-sided alpha of 0.10, there would be 90% power to detect an absolute 20% difference in undetectable prostate-specific antigen (PSA; ≤ 0.2 ng/mL) rate at 28 weeks (relative risk, 1.44); this end point was previously strongly correlated with survival. Secondary end points included the proportion of patients with PSA > 4.0 ng/mL, safety and tolerability, circulating tumor cell (CTC) levels, and seven plasma IGF-IR biomarkers. Fisher's exact test was used for the primary end point, and extended Mantel-Haenszel χ(2) test was used for three PSA response categories. RESULTS: The trial accrued 210 eligible patients (105 randomly assigned to each arm). Patient characteristics were similar in both arms. Undetectable PSA rate was 42 (40.0%) of 105 for cixutumumab plus AD and 34 (32.3%) of 105 for AD alone (relative risk, 1.24; one-sided P = .16). Lower baseline CTCs (0 v 1 to 4 v ≥ 5/7.5 mL whole blood) were associated with higher rate of PSA response (three categories; P = .036) in 39 evaluable patients. IGF-IR biomarkers were not correlated with PSA outcome, and cixutumumab did not significantly change these biomarker levels. CONCLUSION:Cixutumumab plus AD did not significantly increase the undetectable PSA rate in men with new metastatic hormone-sensitive prostate cancer. CTCs at baseline may carry prognostic value.
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