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Cixutumumab fails to enhance activity of ADT in prostate cancer
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The addition of cixutumumab to androgen deprivation therapy did not significantly increase the undetectable PSA rate in patients with new metastatic hormone-sensitive prostate cancer, according to results of a randomized phase 2 study.
Previous studies of cixutumumab (IMC-A12, ImClone Systems) — which targets the insulin-like growth factor I receptor (IGF-IR) — have demonstrated biologic and clinical activity in men undergoing treatment for prostate cancer, according to study background.
Evan Y. Yu, MD, of the division of oncology at the University of Washington, and colleagues evaluated data from 210 patients with new metastatic prostate cancer. Researchers randomly assigned patients 1:1 to ADT with or without cixutumumab within 30 days.
Baseline demographics in the cixutumumab plus ADT arm (mean age, 65 years; range, 60-72) and the ADT alone arm (mean age, 66; range, 58-73) were similar.
Patients received a daily oral dose of ADT plus IV cixutumumab (10 mg/kg) every 2 weeks in the cixutumumab arm and daily ADT alone for seven cycles in the comparison arm. Treatment continued for seven cycles (28 weeks) or until early disease progression, unacceptable toxicity or patient withdrawal.
Undetectable PSA rate (≤ 0.2 ng/mL) after seven cycles served as the primary endpoint. A PSA rate greater than 4 ng/mL served as a secondary endpoint.
Overall, 40% (n = 42) of patients who received cixutumumab plus ADT achieved an undetectable PSA rate at the end of 28 weeks compared with 32.3% (n = 34) of patients who received ADT alone. A comparable portion of men in each arm also demonstrated a PSA rate greater than 4 ng/mL (43.8% vs. 53.3%).
Researchers did not detect a statistically significant difference when aggregate PSA rates were compared. Castration resistance was slightly higher among patients in the cixutumumab arm, although not statistically different (22 vs. 17; RR = 1.29).
Data from 39 evaluable patients indicated that lower baseline circulating tumor cells (0 vs. 1-4 vs. ≥ 5 per 7.5 mL whole blood) were associated with a higher rate of PSA response (P = .036). Additional biomarker analyses indicated IGF-IR was not associated with PSA outcome, and cixutumumab had no significant impact on IGF-IR levels.
Cixutumumab was well tolerated, and no grade 4 or 5 adverse events occurred. Hypoglycemia was the most commonly reported grade 3 adverse event. Only two patients in the cixutumumab arm discontinued treatment due to toxicity.
“Patients in our trial will continue to be observed for OS outcomes, and a prespecified secondary endpoint allows for validation of the undetectable PSA correlation with OS,” Yu and colleagues concluded. “Should the prognostic value of the undetectable PSA model be validated in our trial, future testing of novel therapeutics in the metastatic hormone-sensitive prostate cancer setting will be facilitated with this earlier readout.” – by Cameron Kelsall
Disclosure: Yu reports honoraria, research funding and travel expenses from and consultant roles with Agensys, Amgen, Astellas Pharma, Bayer, Bristol-Myers Squibb, Dendreon, Genentech/Roche, GTx, ImClone, Janssen Pharmaceuticals, Medivation, Oncogenex and
Sanofi-Aventis. Please see the full study for a list of all other authors’ relevant financial disclosures.
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