STAMPEDE update: Durable OS benefit with docetaxel added to ADT in mHNPC

The addition of upfront docetaxel chemotherapy to androgen deprivation therapy (ADT) confers durable and clinically significant benefit in men with hormone-naïve metastatic prostate cancer (mHNPC) regardless of metastatic burden, according to a long-term follow-up of the phase III STAMPEDE* trial reported at ESMO 2019.

“Docetaxel, in combination with ADT, improves overall survival (OS) and failure-free survival (FFS) in newly diagnosed mHNPC,” said study author Professor Nicholas James from the Queen Elizabeth Hospital and the University of Birmingham both in Birmingham, UK. “It should now be considered as a first-line option alongside [androgen receptor]-targeting agents for fit patients with mHNPC  irrespective of stratification for disease burden.” [ESMO 2019, abstract 844O]

The STAMPEDE trial consortium had previously reported an improved OS with upfront docetaxel for metastatic hormone naïve prostate cancer patients commencing long-term ADT. [Lancet 2016;387:1163–1177] James reported the  long-term outcomes stratified by metastatic burden for M1 patients at ESMO 2019, using the CHAARTED definition of high-burden and low-burden baseline disease.

The analysis used Cox regression models, adjusted for all stratification factors, with emphasis on restricted mean survival time if hazards were non-proportional. Retrospectively-collected imaging data, blinded to trial arm, was used to categorize patients as having a low- or high-burden disease.

M1 patients (n=1086) were randomized to receive standard of care (SOC, n=724) or SOC + docetaxel (n=362). Metastatic burden was assessable for 830 of 1,086 patients; 362 of whom had low and 468 had high metastatic burden. Median follow-up was 6.5 years, up from 3.5 years when STAMPEDE results were last reported.

Overall, there were 719 deaths – 494 in the SOC group (41 percent higher than the previous report) vs 225 in the docetaxel group. The addition of docetaxel to ADT significantly improved median OS (59.1 months vs 43.1 months for SOC; hazard ratio [HR], 0.81, 95 percent confidence interval [CI], 0.69–0.95; p=0.009).

Additionally, there was no difference in OS benefit with docetaxel between men with low disease burden (HR, 0.76, 95 percent CI, 0.54–1.07) or high disease burden (HR, 0.81, 95 percent CI, 0.64–1.02).

The addition of docetaxel also improved FFS (HR, 0.66, 95 percent CI, 0.57–0.76) and progression-free survival (PFS; HR, 0.69, 95 percent CI, 0.59–0.81), with no difference in outcomes between the metastatic burden subgroups.

Moreover, docetaxel did not increase the rate of Grade 3–5 adverse events after 1 year vs SOC (27 percent vs 28 percent).

“This analysis does not support the presence of a volume effect on docetaxel effect in men with newly diagnosed metastatic prostate cancer,” James said. “Metastatic burden is, however, prognostic, which is consistent with what we have seen before.”

“This updated report, with long-term follow-up, and metastatic burden sub-group analysis, reinforces the benefits of adding docetaxel to ADT in mHNPC,” said James. “The combination treatment prolongs survival and a delays time to metastatic progression and subsequent therapy. Importantly, this benefit is seen irrespective of metastatic burden, with no evidence of heterogeneity between the low and high metastatic burden sub-groups across any outcome measures. Again, this reinforces the principle that ADT and docetaxel can be considered as an effective first-line treatment option for men with mHNPC regardless of metastatic burden.”