Adding docetaxel to antiandrogen treatment improves progression-free survival (PFS) in prostate cancer patients with prostate-specific antigen (PSA) relapse.
Dr. Andreas Josefsson (Sahlgrenska University Hospital, Göteborg, Sweden) presented the SPCG-14 study, a prospective, multicentre, phase-2 clinical trial of bicalutamide alone or with the addition of docetaxel in nonmetastatic prostate cancer with a rising PSA1. This trial assessed whether any benefit is gained by adding docetaxel-based chemotherapy to hormonal therapy alone in the population of prostate cancer patients who only have a biochemically-relapsed disease after curative treatment (PSA doubling time is <12 months). The investigators hypothesized further that the approach is likely to be more effective at a time of minimal tumor burden, prior to radiographic relapse, resulting in minimization of the overall burden of therapy and better quality of life while on treatment.
A total of 345 patients were randomized 1:1. The control arm (n=174) received antiandrogen (bicalutamide 150 mg once daily) alone. The experimental arm (n=171) received treatment with docetaxel (75 mg/m2 every 3 weeks) for 10 cycles and antiandrogen (bicalutamide 150 mg once daily) treatment. The median participant age was 68 years and the majority of patients had Gleason grade ≤7 (73%) with 26% having Gleason grade ≥8. The primary endpoint was PFS, defined as a PSA of >2 mg/mL above nadir, metastasis, or death due to any cause.
With a median follow-up of 36 months, 5-year progression occurred in 46% of all patients; 15% developed metastatic disease and 10% of patients died. Among those with no progression, the median follow-up was 47 months. The primary endpoint was met; improved PFS was reached by patients receiving bicalutamide plus docetaxel as compared with bicalutamide alone (HR 0.72; 95% CI 0.52-0.99; P=0.041). There were no differences between subgroups of patients based on prior curative-intent treatment, PSA doubling time <6 months, or based on age.
With regard to safety outcomes, toxicity was substantial. The most common serious adverse event was febrile neutropenia (26%). Notably, 62% of participants in the investigation arm terminated docetaxel treatment as a result of adverse events or serious adverse events.
In the era of apalutamide, darolutamide, and enzalutamide, where demonstrated effects on metastasis-free survival and/or overall survival have been recently reported, the current data showing improvement in PFS may not appear practice-changing. However, the wide access of docetaxel does place this regimen, with strong clinical evidence, as an acceptable option for some situations.
Reference:
1. Josefsson AS, et al. A prospective randomised study of bicalutamide +/- docetaxel for non-metastatic prostate cancer with a rising PSA (SPCG-14). EAU20 Virtual Congress, 17-26 July 2020, Game-changing Session 4.