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WASHINGTON -- Sequencing docetaxel prior to second-generation androgen-blocking therapies may improve survival outcomes for men with metastatic castration-resistant prostate cancer (mCRPC), a retrospective study suggested.

Among over 100 patients in the single-center analysis, 3-year cancer-specific survival rates were 88.0% for those treated with docetaxel first, as compared with 64.1% for those who received either abiraterone acetate (Zytiga) or enzalutamide (Xtandi) before the chemotherapy (HR 3.6, 95% CI 1.7-9.5, P=0.01), reported Jack Andrews, MD, of the Mayo Clinic in Rochester, Minnesota.

Additionally, overall survival at 3 years was 82.4% in the docetaxel-first group and 60.8% in the abiraterone- or enzalutamide-first group (HR 2.29, 95% CI 1.1-4.8, P=0.03).

"This is the first study to compare what order would be best for the first-line treatment of mCRPC, and it looks like sequence does impact survival outcomes," Andrews told 番茄社区app during a poster session here at the Society of Urologic Oncology meeting. "If we're considering it, we should consider docetaxel first."

He added that the findings also held true in a subset analysis that was restricted to patients with higher disease volume (it excluded those with lymph-node only metastasis).

Results of the analysis appear to be consistent with the CHAARTED and STAMPEDE trials in the hormone-sensitive setting, Andrews noted.

"Earlier chemotherapy, earlier intensification, has increased benefit rather than using it later," he said.

Sequencing of chemotherapy and newer first-line agents like abiraterone and enzalutamide in mCRPC has not been described in national guidelines or the literature, said Andrews.

In a randomized phase II trial, recently published in the , researchers looked at the sequence of abiraterone followed by enzalutamide versus enzalutamide followed by abiraterone but this was in a group of mostly chemotherapy-naive mCRPC patients.

There, the time to first prostate-specific antigen (PSA) progression was similar for the two drugs in first-line, but patients who received abiraterone first then had a longer time to second PSA progression, at a median of 19.3 months versus 15.2 months for those that received enzalutamide first (HR 0.66, 95% CI 0.45-0.97, P=0.036). And just 4% of patients had a PSA response to abiraterone as second-line therapy versus 36% for those treated with enzalutamide in second-line.

Andrews pointed out, however, that most clinicians typically don't opt for two second-generation androgen-blocking therapies back to back, suggesting that the findings from his group may have more clinical relevance.

"Usually you do an androgen deprivation and then a chemo, or chemo and then androgen deprivation," he said. "And so I think these results, at least in our practice, impact what we do more than abi or enza first."

The Lancet Oncology data may suggest switching to abiraterone after docetaxel, "but that hasn't been proven in studies in the post-chemo setting," he cautioned.

For their study, his group examined 121 mCRPC patients who received either docetaxel followed by a second-generation androgen therapy (n=80) or one of these agents followed by docetaxel (n=32) at the Mayo Clinic from 2011 to 2017. All patients had been naive to chemotherapy or second-generation androgen-blocking therapies prior to the start of treatment. Median follow-up for the survival analysis was 3.4 years.

Inclusion criteria for the analysis included receipt of six cycles of docetaxel (no more or less), and patients went on to second-line therapy following radiographic or PSA progression. Patient characteristics were well-balanced, with no statistical differences between the groups, said Andrews. No differences in patterns of treatments were seen regarding when patients were more likely to get docetaxel first versus abiraterone or enzalutamide first.

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