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Sandy Srinivas, MD
Sandy Srinivas, MD
Posted: Thursday, October 6, 2022
Research presented at the European Society for Medical Oncology (ESMO) Congress 2022 (Abstract 454O) suggests that a combination treatment of the selective CXCR2 antagonist AZD5069 plus enzalutamide may be safe and effective in some patients with metastatic castration-resistant prostate cancer. The disruption of the CXCR2 receptor axis may prove to be able to overturn resistance to enzalutamide driven by tumor-infiltrating myeloid cells.
“We provide clinical evidence for direct targeting of myeloid chemotaxis as a therapeutic strategy in [metastatic castration-resistant prostate cancer],” concluded Christina Guo, MBBS, of the Institute of Cancer Research, London, and colleagues.
The study included 21 patients in phase I and 11 patients in phase II. Eligible patients had experienced disease progression while receiving one novel antiandrogen therapy; the median number of previous lines of therapy was six. Phase I, designed to evaluate dose escalation, included patients who received 160 mg of daily enzalutamide plus 40, 80, 120, 160, or 320 mg of AZD5069 twice daily. Antitumor activity was noted at the 160-mg dose level. The AZD5069 dose was escalated to 320 mg twice daily after pharmacokinetic studies indicated that CYP3A4 AZD5069 metabolism was spurred by enzalutamide.
Afebrile, uncomplicated neutropenia was the main grade 3 or 4 treatment-emergent adverse event, occurring in 11 patients in phase I and 4 patients in phase II. Of the patients enrolled in phase I, three experienced partial responses, and two had stable disease for more than 6 months. Stable disease was achieved by one patient at the 80-mg dose level and one at the 160-mg dose level. Partial responses were observed in one patient at each of the following dose levels: 120 mg, 160 mg, and 320 mg. Among patients enrolled in phase II, one achieved stable disease, and one experienced a 33% decline in prostate-specific antigen level.
Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com.
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