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

The addition of enzalutamide to abiraterone acetate plus prednisone (AAP) did not improve overall survival (OS) of patients with metastatic hormone-sensitive prostate cancer (mHSPC), the results from the analysis of 2 phase 3 STAMPEDE platform trials demonstrated. The survival benefit of AAP, when added to androgen deprivation therapy (ADT), was maintained at 7 years.

The addition of either AAP or enzalutamide to ADT has been shown to improve mHSPC disease outcomes in men [1,2]. Combining AAP and enzalutamide improved progression-free survival (PFS), but not OS, in patients with metastatic castration-resistant prostate cancer (mCRPC) [3]. However, the benefits of combining AAP and enzalutamide in mHSPC are unknown. Additionally, survival outcomes of mHSPC patients on ADT plus AAP or AAP plus enzalutamide beyond 5 years have not been reported. The results from a comparison of 2 randomised phase 3 trials in the multi-arm, multi-stage STAMPEDE platform (NCT00268476) were presented by Prof. Gerhardt Attard (UCL Cancer Institute London, UK) [4].

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

The median follow-up was 95.8 months in the AAP trial and 71.7 months in the AAP plus 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 plus enzalutamide vs SOC, P<0.0001; see Figure). No evidence was seen of a difference in the treatment effect (interaction HR 1.05; P=0.71) between both trials. At 84 months of follow-up, 48% of participants treated with ADT plus AAP were still alive compared with 30% of participants treated with ADT alone.

The rates of adverse events were similar in both trials. However, adverse events occurred more frequently in patients treated with AAP plus 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 plus enzalutamide.

Based on these results, Prof. Attard concluded that “enzalutamide and AAP should not be combined for treating patients with mHSPC. It does not improve survival and only increases the incidence of adverse events. Additionally, these results show that the survival benefit of AAP plus ADT is maintained at 7 years.”

1. James ND, et al. N Engl J Med. 2017;377(4):338–351.
2. Davis ID, et al. N Engl J Med 2019;381(2):121–131.
3. Morris MJ, et al. J Clin Oncol. 2019;37(15_suppl):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, 09–13 September, Paris, France.

Figure: Overall survival curves per treatment arm: AAP and AAP+ enzalutamide [4].



SOC, standard-of-care. AAP, abiraterone acetate plus prednisolone. ENZ, enzalutamide. ADT, androgen deprivation therapy.



Posted on 17 November, 202218 March, 2024