No Improvement in Undetectable PSA Rate With Cixutumumab Plus Androgen-Deprivation Therapy in Metastatic Hormone-Sensitive Prostate Cancer
In a randomized phase II trial (SWOG S0925) reported in the Journal of Clinical Oncology, Yu et al found that the addition of cixutumumab to androgen-deprivation therapy did not significantly increase the rate of undetectable prostate-specific antigen (PSA) in patients with newly diagnosed metastatic hormone-sensitive prostate cancer. Cixutumumab inhibits the insulin-like growth factor I receptor (IGF-IR).
Study Details
In the study, 210 patients from SWOG institutions were randomly assigned between February 2011 and December 2012 within 30 days of starting androgen deprivation to receive bicalutamide daily with a luteinizing hormone-releasing hormone agonist alone (n = 105) or with cixutumumab at 10 mg/kg given intravenously over 1 hour every 2 weeks for seven 28-day cycles. The primary endpoint was rate of undetectable PSA (≤ 0.2 ng/mL) at 28 weeks.
The cixutumumab and control groups were generally balanced for baseline characteristics, including age (median, 65 and 66 years), PSA level (median, 31 and 37 ng/mL), Gleason score (≥7 in 60% and 78%), race (89% and 84% white), metastasis site (lymph node only in 14% and 9%, bone only in 53% and 60%, both in 18% and 16%, visceral in 14% and 15%), and early-induction androgen deprivation (56% and 62%).
No Significant Increase in Undetectable Rate
The rate of undetectable PSA was 40.0% in the cixutumumab group vs 32.3% in the androgen-deprivation therapy–alone group (relative risk = 1.24, one-sided P = .16). PSA > 0.2 to ≤ 4.0 ng/mL was observed in 16.2% vs 14.3%, and PSA > 4.0 ng/mL was observed in 43.8% vs 53.3%.
Among 39 patients evaluable for circulating tumor cell levels, lower baseline levels (0 vs1 to 4 vs ≥ 5/7.5 mL) were associated with higher rate of PSA response (P = .036 for trend). IGF-IR biomarkers assessed in a subgroup of patients were not associated with PSA results, and no effect of cixutumumab on biomarker levels was observed.
Adverse Events
The most common grade 3 adverse events in the cixutumumab group were hyperglycemia (8% vs 0% in the control group) and hypertension (2% vs 2%). In the cixutumumab group, adverse events led to dose interruption in 18%, reduction in 8%, and discontinuation in 2%.
The investigators concluded “Cixutumumab plus [androgen deprivation] did not significantly increase the undetectable PSA rate in men with new metastatic hormone-sensitive prostate cancer. [Circulating tumor cells] at baseline may carry prognostic value.”
Evan Y. Yu, MD, of University of Washington, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by the National Cancer Institute, ImClone Systems (subsidiary of Eli Lilly), and Veridex (Janssen Diagnostics/Johnson & Johnson).
For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
