Enzalutamide Plus Abiraterone May Have Higher Response Rate in mCRPC Than Either Agent Alone
... In several studies, Efstathiou and colleagues first demonstrated that treatment with abiraterone acetate, an androgen biosynthesis inhibitor, reduced testosterone levels in the blood and bone marrow to undetectable levels. “Soon after initiation of treatment, however, we observed a compensatory feedback mechanism leading to an increase in androgen receptor copy numbers as a result of testosterone depletion,” she said. Similarly, following inhibition of nuclear androgen receptor (AR) localization with enzalutamide (an AR inhibitor), they observed an induction of testosterone both in the blood and bone marrow—“suggesting that there is a feedback mechanism leading to an increase in testosterone,” she added.
“No new safety concerns have arisen,” Efstathiou said. Two patients discontinued treatment due to adverse events, but no grade 4 or 5 toxicities have been observed thus far—a sign that the combination approach is reasonably well tolerated, she added.
"In 49 patients evaluable for disease impact, investigators also noted significant declines in PSA levels. At a median of 5.5 months of treatment exposure, approximately 45% of the 49 evaluable patients had a 90% or greater decline in PSA from baseline. Three-quarters of the group achieved a 50% or greater decline in PSA values from baseline while approximately 84% achieved a 30% or greater decline from baseline PSA values.
Nevertheless, he cautioned that comparable declines in PSA in comparable proportions of patients have been reported by other investigators following treatment with either drug alone. “This is only a single-arm study of 2 highly active drugs, and this really limits any conclusion on the increased activity of the 2 drugs given together,” he said."
The point here might be the durability of this response rather than the maximum magnitude of it.
None of this matters to Cabo. Sooner or later, metastatic prostate cancer becomes resistant to all hormone manipulations. No one will be cured by the combination. Cabo will play an important role after the hormones fail