Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Men with metastatic castration-resistant prostate cancer (mCRPC) who progress after an initial response to enzalutamide may have better progression-free survival (PFS) if they continue with the anti-androgen agent during docetaxel chemotherapy, suggests research presented at the 2022 ASCO Genitourinary Cancers Symposium in San Francisco, California, USA.
The PRESIDE investigators hypothesised that continuation of enzalutamide after progression might help “maintain control of responsive tumor lesions and enable docetaxel to target clonal subpopulations that adopted accessory pathways to enhance survival and proliferation.”
To investigate, 687 men with chemotherapy-naïve mCRPC and minimal or no symptoms were given open-label enzalutamide 160 mg/day. In all, 273 patients had a confirmed response at week 13 and were followed up until disease progression, at which time they were randomly assigned to continue enzalutamide (n=136) or switch to placebo (n=135) while beginning docetaxel chemotherapy.
Presenting author Axel Merseburger, from Universitätsklinikum Schleswig-Holstein, Lübeck, Germany, reported that the phase IIIb trial’s primary endpoint of PFS was met, with a median duration of 9.53 months with enzalutamide during docetaxel treatment and 8.28 months with placebo, giving a significant hazard ratio (HR) of 0.72.
The results of the subgroup analyses were “consistent” with the overall finding, although the investigator noted that there may be a greater PFS benefit with continuing enzalutamide among men who had visceral metastases.
There was also a significant improvement in time to prostate-specific antigen (PSA) progression with enzalutamide versus placebo (median 8.44 vs 6.24 months; HR=0.58) and, on average, men who continued with enzalutamide had a greater decrease in PSA between randomisation and week 13 (–37.12 vs 9.11%).
In addition, there was a numerically higher rate of objective responses with enzalutamide than placebo (31.6 vs 25.9%), although this difference did not reach significance.
Turning to treatment-emergent adverse events (TEAEs), Axel Merseburger said that enzalutamide plus docetaxel had “an acceptable safety profile consistent with the known safety profiles of these drugs”.
The most common TEAEs in the enzalutamide plus docetaxel arm were asthenia (34.6%), neutropenia (33.8%) and alopecia (32.4%) whereas the most frequent TEAEs with placebo plus docetaxel were neutropenia (33.3%), diarrhoea (32.6%) and alopecia (27.4%).
After initial enzalutamide treatment lasting a median 62.6 weeks, patients continuing with enzalutamide had an additional median 36.1 weeks of enzalutamide exposure versus a median 30.1 weeks of placebo, with a median 6.9 and 7.0 cycles of docetaxel given to the groups, respectively.
“These data suggest that continued treatment with enzalutamide plus docetaxel offers clinical benefit and could be a future treatment for some patients who progress on enzalutamide alone”, concluded Axel Merseburger.
Session discussant Elisabeth Heath, from Wayne State University in Detroit, Michigan, USA, said that the PFS gain with continued enzalutamide has “clinical benefit” and “meaning” from a patient’s perspective in the absence of more severe toxicity. But she noted that the complexity of the trial design meant PRESIDE would be unlikely to demonstrate an overall survival advantage.
While Elisabeth Heath ruled out continuing enzalutamide during docetaxel chemotherapy becoming a new standard of care, the discussant emphasized that that the regimen should be considered as a treatment option for men who progress on enzalutamide after initial response and are suitable candidates for combination therapy.
Merseburger AS, Attard G, Boysen G, 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 treated with docetaxel (DOC) plus prednisolone (PDN) who have progressed on ENZA: PRESIDE. J Clin Oncol 2022;40(suppl 6; abstr 15). DOI: 10.1200/JCO.2022.40.6_suppl.015
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