Continued enzalutamide plus docetaxel offers clinical benefit for mCRPC patients who progress on enzalutamide

In patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel plus prednisolone who have progressed on enzalutamide, the continuation of enzalutamide plus docetaxel led to a significant improvement of progression-free survival (PFS), results from the phase 3 PRESIDE study showed.

Treatment with enzalutamide plus androgen deprivation therapy (ADT) significantly reduced the risk of metastatic progression or death over time versus placebo plus ADT in men with metastatic hormone-sensitive prostate cancer (mHSPC) or non-metastatic castration-resistant prostate cancer (nmCRPC) [1,2].

The phase 3 PRESIDE trial (NCT02288247) evaluated the benefit of continuation of enzalutamide plus ADT plus docetaxel in men with mCRPC who progressed on enzalutamide plus ADT. The study enrolled chemotherapy-naïve men with mCRPC who had disease progression while on ADT or after bilateral orchiectomy. In the open-label Period 1 of the study, 687 patients received enzalutamide, of whom 271 showed disease progression and were eligible for randomisation in double-blind Period 2 of the study. In Period 2, participants were 1:1 randomised to treatment with enzalutamide/docetaxel/prednisolone/ADT or placebo/docetaxel/prednisolone/ADT. The primary endpoint was PFS in Period 2. Secondary endpoints included time to PSA progression and PSA response in Period 2. Dr Axel Merseburger (Universitätsklinikum Schleswig-Holstein, Germany) presented the results [3].

Median enzalutamide exposure was 62.6 weeks in Period 1 and 36.1 and 30.1 weeks in Period 2 with enzalutamide and placebo, respectively. At the Period 2 data cut-off, 269 (99.3%) participants had discontinued therapy; 93 in each arm had progression (enzalutamide: 74.4%; placebo: 75.6%). PFS was significantly longer with enzalutamide than placebo (9.53 vs 8.28 months; HR 0.72; P=0.027). A benefit of enzalutamide was observed in all subgroups and most pronounced in patients with visceral disease. Enzalutamide also significantly reduced time to PSA progression (8.44 vs 6.24 months; HR 0.58; P=0.002). There was a greater decrease in PSA levels form baseline within the enzalutamide group (-37.1%) compared with the placebo group (+9.1%) at week 13 of Period 2.

In Period 2, 264 (97.4%) participants had a treatment-emergent adverse event (TEAE). TEAE rates were comparable in both arms (enzalutamide 97.8%, placebo 97.0%). Grade 3/4 TEAEs were reported by 61.8% of participants on enzalutamide 62.2% of participants on placebo; 8.8% and 6.7% of participants, respectively, had TEAEs leading to discontinuation.

“In patients who progressed on enzalutamide, continued enzalutamide treatment in combination with docetaxel led to a significant improvement in PFS compared with placebo plus docetaxel,” concluded Dr Merseburger. “In addition, enzalutamide favoured time to PSA progression and PSA response data. Therefore, continued treatment with enzalutamide plus docetaxel offers clinical benefit and could be a future treatment option for patients who progress on enzalutamide alone.”

1. Armstrong AJ, et al. J Clin Oncol. 2019;37:2974–2986.
2. Hussain H, et al. N Engl J Med 2018;378:2465–2474.
3. Merseburger A, et al. A randomized, double-blind, placebo (PBO)-controlled, phase 3b study of the efficacy and safety of continuing enzalutamide (ENZA) in chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with docetaxel (DOC) plus prednisolone (PDN) who have progressed on ENZA: PRESIDE. Abstract 15, ASCO GU 2022, 17–19 February.

 

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Posted on 8 April 202217 May 2024