Intermittent Docetaxel Non-Inferior to Continuous Therapy in CRPC

June 7, 2016

An intermittent docetaxel regimen was non-inferior to continuous docetaxel therapy in patients with metastatic castration-resistant prostate cancer.

An intermittent docetaxel regimen was non-inferior to continuous docetaxel therapy in patients with metastatic castration-resistant prostate cancer, according to results of a phase III trial presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago (abstract 5005).

The PRINCE study compared a standard docetaxel regimen with a regimen in which the therapy is paused. “The rationale of intermittent therapy and the benefit this might hold for the patient is clearly the treatment holiday,” said Hannes Cash, MD, of Charité University Medicine Berlin in Germany, who presented the study. “With this, [there is] reduced docetaxel exposure for the patient, reduced cumulative toxicities, and possibly delayed resistance to taxanes.” He noted that the study began in 2005, when there was a need to improve docetaxel therapy and some of the newer agents were not yet available.

A total of 187 patients (156 evaluable) were randomized to receive standard continuous docetaxel treatment vs an intermittent regimen involving 12 weeks of treatment followed by a pause until disease progression, when docetaxel was started again. Progression was defined as either serum prostate-specific antigen (PSA) > 4 ng/mL with a 50% increase over baseline level, or radiological or symptomatic progression.

The 1-year survival rate in the continuous therapy group was 75%, compared with 78% in the intermittent group; this met the non-inferiority criteria for the study. As expected, the intermittent patients received a lower cumulative dose of docetaxel (368.16 mg/m2) compared with the continuous patients (444.2 mg/m2), but that difference was not statistically significant (P = .84).

The median overall survival was 18.3 months with continuous docetaxel and 19.3 months with intermittent treatment, for a hazard ratio of 1.14 (95% CI, 0.75–1.72; P = .535); a post-hoc analysis determined that this did not meet the non-inferiority criteria. Differences between the two groups with regard to progression-free survival and time to treatment failure were not significant.

“The lower cumulative dose did not translate into a lower rate of adverse effects,” Cash said. There were no differences between groups with regard to grade 3 or 4 anemia or neutropenia, fatigue, and other events. Cash noted that the study did not end up recruiting its full planned cohort, and thus it remains “speculative” what the outcomes may have been with more patients. He concluded that based on this data, though, this regimen may be offered to metastatic prostate cancer patients.

The discussant for the session, Derek Raghavan, MD, PhD, of the Levine Cancer Institute in Charlotte, North Carolina, said that he thinks “it is reasonable to offer patients a chemo holiday.” He noted that this can reduce costs of therapy without a significant detriment to patients.