Cixutumumab plus androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer produced an insignificant improvement over androgen deprivation alone in undetectable PSA rate after 28 weeks, according to researchers. The report was published online April 6 in the Journal of Clinical Oncology.
After 28 weeks of therapy, 40% of the androgen deprivation (AD) plus cixutumumab arm (42/105) had undetectable PSA compared with 32.3% (34/105) of the AD alone arm (RR, 1.24; one-sided P = .16)
In addition, 35 patients were evaluated for plasma biomarkers hypothesized to be affected by IGF-1R inhibition, but none of the markers were significantly associated with PSA response. “Patients in our trial will continue to be observed for overall survival outcomes, and a prespecified secondary endpoint allows for validation of the undetectable PSA correlation with overall survival. This will be of great interest,” wrote Dr. Evan Yu of University of Washington, Seattle, and associates (J. Clin. Oncol. 2015 April 6 [doi:10.1200/JCO.2014.59.4127]).
“Should the prognostic value of the undetectable PSA model be validated in our trial, future testing of novel therapeutics in the metastatic HSPC setting will be facilitated with this earlier readout,” they said.
The authors chose a short, 28-week endpoint to get an early signal to determine the potential value of a larger phase III trial, and to avoid committing resources and patients to a potentially ineffective therapy.
Preclinical studies using murine xenografts indicated that cixutumumab, a monoclonal antibody specific for insulin-like growth factor 1 receptor (IGF-1R), induces IGF-1R internalization and leads to cancer cell apoptosis in HSPC. However, the xenograft studies may not have adequately modeled the human disease due to the nature of the immunocompromised mouse, intraperitoneal rather than intravenous antibody administration, or the characteristics of the xenograft. Given patient and tumor heterogeneity, multiple xenograft models would provide a more robust model system.
Despite negative results from this trial, Dr. Yu and colleagues wrote, “rationale exists for other combinations with cixutumumab, such as docetaxel or mammalian target of rapamycin inhibitors like temsirolimus.”