medwireNews: A sequencing strategy that uses abiraterone acetate plus prednisone followed by enzalutamide, rather than the opposite, provides the greatest clinical benefit to patients with newly diagnosed metastatic castration-resistant prostate cancer (mCRPC), researchers report.
This is because “[e]nzalutamide showed activity as a second-line novel androgen receptor pathway inhibitor, whereas abiraterone acetate did not, leading to a longer time to second PSA [prostate-specific antigen] progression for the sequence of abiraterone followed by enzalutamide than with the opposite treatment sequence,” write Kim Chi (BC Cancer, Vancouver, British Columbia, Canada) and co-authors in The Lancet Oncology.
The multicenter, phase II, crossover trial included 202 men who were randomly assigned to receive either oral abiraterone acetate 1000 mg once daily plus oral prednisone 5 mg twice daily until PSA progression followed by crossover to oral enzalutamide 160 mg once daily (group A; n=101), or to the reverse sequence (group B; n=101).
After a median 30.7 months of follow-up, 72% of patients in group A and 74% of those in group B had crossed over to their second treatment.
Following crossover, Chi and team found that the median time to second PSA progression (defined as an increase of 2 μg/L and 25% from nadir) was significantly longer in group A than in group B, at 19.3 versus 15.2 months, and a hazard ratio 0.66.
In addition, significantly more patients in group A than in group B had a PSA response (≥30% decline from baseline) on second-line therapy, at 36% for enzalutamide versus 4% for abiraterone.
Median overall survival time was 28.8 months in group A and 24.7 months in group B, with no significant difference between the two sequences.
When considering just first-line therapy, the researchers observed that the PSA response rate was significantly lower with abiraterone plus prednisone, at 68%, than with enzalutamide, at 82%, but time to PSA progression was comparable (median, 11.2 vs 10.2 months).
The investigators also note that the “[i]ncidence and severity of adverse events of interest were consistent with the known toxicity profile of both drugs.”
Chi and co-authors believe their findings “are the first prospective data estimating the degree of cross-resistance for both sequences, as well as the first randomised comparison of both treatment sequences in their entirety.”
They say: “Overall, our findings show that alternating androgen receptor pathway inhibitors at progression can be beneficial when abiraterone plus prednisone is used first.
“However, because of the modest response to second-line enzalutamide, other available and appropriate therapies should also be considered for patients progressing after first-line androgen receptor pathway inhibitors, such as taxane chemotherapy and radium-223.”
By Laura Cowen
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