Docetaxel/SOC Significantly Reduces Mortality in Low PSA Prostate Cancer

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Docetaxel plus standard of care may be beneficial among patients with prostate cancer and low prostate-specific antigen levels who do not have any highly effective treatment options, says Anthony D’ Amico, MD, PhD.

"[Docetaxel plus standard of care yields] a marked improvement in survival for these patients, who currently do not have any highly effective treatments," according to Anthony V. D’Amico, MD, PhD.

"[Docetaxel plus standard of care yields] a marked improvement in survival for these patients, who currently do not have any highly effective treatments," according to Anthony V. D’Amico, MD, PhD.

Combining docetaxel with standard-of-care therapy resulted in a significant reduction in prostate cancer-specific mortality (PCSM) among patients with high-grade prostate cancer and low prostate-specific antigen (PSA) levels, according to findings from a meta-analysis published in JAMA Network Open.1

Investigators highlighted a nonsignificant reduction in the risk of all-cause mortality (ACM; HR, 0.51; 95% CI, 0.24-1.09) and PCSM (subdistribution HR [sHR], 0.42; 95% CI, 0.17-1.02) among all patients receiving docetaxel plus standard of care compared with standard of care alone.2 Among patients with a performance status of 0 (n = 139), docetaxel-based treatment yielded more significant reductions in ACM (HR, 0.46; 95% CI, 0.21-1.02) and PCSM (sHR, 0.30; 95% CI, 0.11-0.86).

The unadjusted estimated 8-year ACM rate among those with a performance status of 0 was 14% (95% CI, 6%-28%) with docetaxel plus standard of care vs 30% (95% CI, 18%-48%) with standard of care alone. Investigators also reported an estimated 8-year PCSM rate of 8% (95% CI, 2%-18%) vs 23% (95% CI, 11%-38%) in each respective arm.

“An excellent [performance status] identifies patients who can tolerate the full course of chemotherapy and therefore benefit if the treatment proves effective,” senior author Anthony V. D’Amico, MD, PhD, chief of Genitourinary Radiation Oncology at Brigham and Women’s Hospital, said in a press release.2 “It's a marked improvement in survival for these patients, who currently do not have any highly effective treatments.”

Investigators of this meta-analysis evaluated data from 5 randomized clinical trials assessing 2597 patients with prostate cancer who received testosterone suppression plus radiotherapy or radical prostatectomy with or without docetaxel. Patients primarily received 3-dimensional radiotherapy, and radiation that was administered to the pelvic lymph nodes in those with a Gleason score of 8 to 10. In the docetaxel arms of each clinical trial, patients received radical prostatectomy as a standard-of-care treatment in combination with androgen deprivation therapy for 18 to 24 weeks.

The co-primary end points of the analysis were ACM and PCSM. Investigators determined causes of death based on trial-defined events.

Patients with localized or locally advanced non-metastatic prostate cancer and a PSA level lower than 4 ng/mL and a Gleason score of 8 to 10 were eligible for inclusion in the meta-analysis. Investigators ultimately identified a final cohort of 145 eligible patients, including 67 who received standard of care alone and 78 who were treated with standard of care and docetaxel.

The median patient age was 63 years (interquartile range, 46-67). Most patients were White (81.4%) followed by Black (4.1%), Asian (3.4%), and other races or ethnicities (1.4%). Additionally, 64.8% of the population proceeded with radical prostatectomy, and 26.2% were treated with androgen deprivation therapy for 2 years.

Overall, 19 patients who received standard of care alone and 12 who were treated with docetaxel plus standard of care died; 15 and 7 deaths in each respective group were due to prostate cancer. Among patients with a performance status of 0, 17 and 10 patients in each respective group died, 14 and 5 deaths of which were associated with prostate cancer.

References

  1. Mahal BA, Kwak L, Xie W, et al. Mortality risk for docetaxel-treated, high-grade prostate cancer with low PSA levels: a meta-analysis. JAMA Netw Open. 2023;6(11):e2340787. doi:10.1001/jamanetworkopen.2023.40787
  2. Docetaxel use associated with significant reduction in prostate cancer death in very poor prognostic group. News release. Brigham and Women’s Hospital. November 1, 2023. Accessed November 7, 2023. https://bit.ly/40sby2O
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