SWOG S0925: A Randomized Phase II Study of Androgen Deprivation Combined With Cixutumumab Versus Androgen Deprivation Alone in Patients With New Metastatic Hormone-Sensitive Prostate Cancer.

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.

• Authors: Evan Y Yu, Hongli Li, Celestia S Higano, Neeraj Agarwal, Sumanta K Pal, Ajjai Alva, Elisabeth I Heath, Elaine T Lam, Shilpa Gupta, Michael B Lilly, Yoshio Inoue, Kim N Chi, Nicholas J Vogelzang, David I Quinn, Heather H Cheng, Stephen R Plymate, Maha Hussain, Catherine M Tangen, Ian M Thompson Jr
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 14 Pg. 1601-8 (May 10 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 25847934 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Androgen Antagonists
• Anilides
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Hormonal
• Biomarkers, Tumor
• Nitriles
• Tosyl Compounds
• cixutumumab
• Gonadotropin-Releasing Hormone
• bicalutamide
• Receptor, IGF Type 1
• Prostate-Specific Antigen

Topics

• Aged
• Androgen Antagonists (therapeutic use)
• Anilides (administration & dosage)
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Hormonal (therapeutic use)
• Biomarkers, Tumor (blood)
• Drug Administration Schedule
• Gonadotropin-Releasing Hormone (agonists)
• Humans
• Logistic Models
• Male
• Middle Aged
• Neoplasm Staging
• Neoplastic Cells, Circulating
• Nitriles (administration & dosage)
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (blood, drug therapy, pathology)
• Receptor, IGF Type 1 (blood)
• Tosyl Compounds (administration & dosage)
• Treatment Outcome