medwireNews: Abiraterone acetate plus prednisone should be used as front-line therapy for metastatic castration-resistant prostate cancer (mCRPC), recommend researchers who found enzalutamide has superior second-line efficacy in this population.
“Our trial is the first, to our knowledge, to show an advantage to using a sequencing strategy of both drugs: the treatment sequence of abiraterone plus prednisone followed by enzalutamide had a longer time to PSA [prostate-specific antigen] progression than did the opposite sequence”, report Kim Chi, from BC Cancer in Vancouver, British Columbia, Canada, and co-workers.
“Our findings are also the first randomised data showing activity of enzalutamide as a second-line treatment targeting the androgen receptor, and minimal activity of second-line abiraterone plus prednisone”, they write in The Lancet Oncology.
After a median 22.8 months of follow-up, cross over to the second-line therapy had occurred in a comparable 72% of the 101 patients given front-line abiraterone acetate 1000 mg/day plus prednisone 5 mg twice daily and 74% of the 101 men who instead received enzalutamide 160 mg/day as their initial treatment.
There was a significantly higher rate of PSA response to second-line enzalutamide than to second-line abiraterone acetate, with a 30% or greater reduction from baseline achieved by 36% of 73 patients versus just 4% of 75 patients, respectively.
And after treatment was switched, the primary endpoint of median time to second PSA progression was significantly longer with front-line abiraterone acetate plus prednisone than with first-line enzalutamide, at 19.3 versus 15.2 months and a hazard ratio for progression of 0.66, say the researchers who, based on these results, describe giving abiraterone first as the “optimal sequencing strategy for these drugs”.
Overall survival after a median of 30.7 months of follow-up was a comparable median 28.8 months with abiraterone acetate first and 24.7 months for enzalutamide first. There were no treatment-related deaths.
The team adds that adverse events were “consistent with the known toxicity profile of both drugs”, with hypertension the most common grade 3–4 event throughout the whole trial in both the front-line abiraterone acetate and enzalutamide arms (27 vs 18%), followed by fatigue (10 vs 4%).
Khalaf DJ, Annala M, Taavitsainen S, et al. Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Lancet Oncol; Advance online publication 11 November 2019. https://doi.org/10.1016/S1470-2045(19)30688-6
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