Overall survival benefit of abiraterone in mHSPC is maintained for 7 years

Addition of enzalutamide to AAP does not improve overall survival of metastatic hormone-sensitive prostate cancer patients, STAMPEDE trial results show.

AAP and enzalutamide combination had shown PFS benefits, but not OS

In recent years, it has been demonstrated that, in men with mHSPC, addition of either AAP or enzalutamide to androgen deprivation therapy (ADT) improves outcomes1,2. Combining AAP and enzalutamide has been shown to benefit progression-free survival (PFS), but not OS, in patients with metastatic castration-resistant prostate cancer (mCRPC)3. However, the benefit of combining AAP and enzalutamide in mHSPC is unknown. In addition, survival outcomes of mHSPC on ADT plus AAP or AAP/enzalutamide beyond 5 years have not been reported. Comparison of 2 randomised phase 3 trials in the multi-arm, multi-stage STAMPEDE protocol (NCT00268476) can give insight in both questions. Dr Gerhardt Attard (UCL Cancer Institute London, UK) presented the results4.

The 2 trials -with no overlapping controls- randomised 1,003 mHSPC patients to ADT plus AAP and 916 mHSPC patients to ADT plus AAP/enzalutamide. Controls were treated with standard-of-care (SOC), being ADT or ADT plus docetaxel. Treatment was continued to progression. The primary outcome of the trials was OS.

Survival benefit of AAP when added to ADT is maintained at 7 years

Median follow-up was 95.8 months in the AAP-trial and 71.7 months in de AAP/enzalutamide trial. In both trials, the addition of second-generation hormonal agent(s) improved OS (HR 0.62 for AAP vs SOC, P<0.0001; HR 0.65 for APP/enzalutamide vs SOC, P<0.0001). No evidence was seen of a difference in treatment effect (interaction HR 1.05; P=0.71) between both trials. At 84 months of follow-up, 48% of patients treated with ADT plus AAP were still alive versus 30% of patients treated with ADT alone.

Rates of adverse events were similar in both trials, however they occurred more common in patients treated with AAP/enzalutamide compared with AAP. Grade 3–5 adverse events in the first 5 years were observed in 54.4% of patients treated with AAP and in 67.9% of patients treated with AAP/enzalutamide. 

Based on these results, Dr Attard concluded that “enzalutamide and AAP should not be combined for treatment of patients with mHSPC. Addition of enzalutamide to APP does not improve survival and only increases the incidence of adverse events. In addition, these results show that the survival benefit of AAP when added to ADT is maintained at 7 years.”

  1. James ND, et al. N Engl J Med. 2017;377:338–351.
  2. Davis ID, et al. N Engl J Med 2019;381:121–131.
  3. Morris MJ, et al. J Clin Oncol. 2019;37:5008.
  4. Attard G, et al. Comparison of abiraterone acetate and prednisolone (AAP) or combination enzalutamide (ENZ) + AAP for metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy (ADT): Overall survival (OS) results of 2 randomised phase III trials from the STAMPEDE protocol. Abstract LBA62, ESMO Congress 2022, Paris, France, 09–13 September.