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Background: We investigated our institution’s mCRPC enzalutamide or abiraterone patients examining PSA responses and impact of sequencing of these drugs. Methods: All enzalutamide / abiraterone mCRPC patients (2011-2018) were included. Rates of PSA >50% response (PSA50) were compared. Time to treatment failure (TTF) and overall survival (OS) was analysed as per lines of previous therapy and timing of chemotherapy. Results: 363 patients included (Enza n=236, Abi n=127), with 15.6 months median follow-up. PSA50 was greater in enzalutamide group (58% vs 31% p<0.0005) but TTF was similar for both groups (median Abi 4.2m vs Enza 6m, p=0.965). There was no significant median OS difference between the groups (Enza 13.8m vs Abi 12.5m p=0.065). Number of lines of prior therapy (p=0.735) or timing of chemotherapy before or after Abi/Enza (p=0.21) had no significant OS impact. Conclusion: Enzalutamide showed higher PSA50 response than abiraterone. Previous lines of therapy or sequencing of chemotherapy with abiraterone / enzalutamide showed no significant survival differences indicating no detriment in either treatment sequence.

Objective: Enzalutamide is effective in treating metastatic castrate-resistant prostate cancer (mCRPC) but can have side effects that require treatment breaks (TB). We conducted a retrospective analysis of outcomes of patients who had extended TB due to toxicity compared to continuous dosing. Methods: Patients prescribed enzalutamide for mCRPC from September 2011 to February 2018 were included. TB was defined as an interruption of four weeks or more. Overall survival (OS) from enzalutamide start, time to prostate-specific antigen failure (TTF) and total enzalutamide treatment time (TTT) were analysed for TB and continuous responders (>50% PSA drop), and a significance level of 0.05 was assigned. Results: A total of 110 patients were continuous responders, and 29 had TB. The median number of interruptions was one (range 1–7), and time on treatment was 70% in the TB group. The TB group had significantly improved OS (100 vs. 60 months; hazard ratio=1.8, 95% confidence interval 1.17–2.77, p=0.02), prolonged TTF (median 11 vs. 6 months; p=0.008) and TTT (median 15 vs. 8 months; p=0.0001). Conclusion: Extended TB do not seem to impact OS or treatment duration adversely in patients who are responding and experiencing toxicity, and may be a useful option in managing toxicity. Prospective trials could explore this further. Level of evidence: Level 2c.

The results of a series of non-randomized studies suggest that complete androgen blockade, i.e. medical or surgical castration in association with an antiandrogen, is superior to castration alone as regard survival potential. This report presents 11 untreated patients (Stage T2-4, Nx, M1), who were treated with complete androgen blockade, orchiectomy and a pure antiandrogen (Flutamide 250 mg three times a day). The rate of subjective response was 100% and the median time to progression was 12 months. The objective response rate was 82% and the rates of partial remission at one and two years were 45% and 18%, respectively. The survival rates after one and two years were 91% and 53%, respectively, a result which is consistent with that of other studies on the survival of patients with metastatic cancer of the prostate treated with either diethylstilboestrol, orchiectomy or LH-releasing hormones. The results of this study do not support the hypothesis that androgen blockade improves the survival of patients with advanced metastatic cancer of the prostate.

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81 Background: Intermittent hormone manipulation in castrate-sensitive prostate cancer can improve quality of life whilst maintaining comparable disease outcomes with continuous scheduling. Enzalutamide is effective in metastatic castrate-resistant prostate cancer (mCRPC) treatment but can have significant side-effects. We conducted a retrospective analysis of patients treated with intermittent enzalutamide compared with continuous dosing. Methods: Patients prescribed enzalutamide for mCRPC at Royal Cornwall Hospital from September 2011 to February 2018 were included. Data was collected from electronic medical records, selecting patients with at least a 1 month treatment break. Kaplan-Meier analysis of overall survival from enzalutamide start (OS), time to PSA failure (TTF) and total enzalutamide treatment time (TTT) was calculated for intermittent and continuous responders (>50% PSA drop), assigned significance level of 0.05. Results: 243 patients received enzalutamide, 110 (45%) were continuous responders and 29 (12%) had intermittent dosing. All patients treated intermittently had a PSA response prior to first treatment break, which was most commonly for fatigue (60%). 25% were still receiving enzalutamide. Median number of breaks was 1 (range 1-7), time on treatment was 70% and time to first break was 5 months. The intermittent group had significantly improved OS with median not reached, median OS for continuous responders was 19 months (HR 2.39, 95% CI 1.53-3.76, p=0.002). The intermittent group had prolonged TTF (median 13 vs 6 months, p=0.001) and TTT (median 30 vs 10 months, p=0.0003). Conclusions: Intermittent dosing of enzalutamide in these mCRPC patients does not adversely impact OS, increasing time patients remain on treatment. However, this was a small, retrospective, single-centre study; prospective trials are necessary to clarify the role of intermittent enzalutamide.[Table: see text]