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) . 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) .
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.”
- James ND, et al. N Engl J Med. 2017;377(4):338–351.
- Davis ID, et al. N Engl J Med 2019;381(2):121–131.
- Morris MJ, et al. J Clin Oncol. 2019;37(15_suppl):5008.
- 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 .
SOC, standard-of-care. AAP, abiraterone acetate plus prednisone. ENZ, enzalutamide. ADT, androgen deprivation therapy.
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Table of Contents: ESMO 2022
Letter from the Editor
High pathological responses to neoadjuvant immune checkpoint inhibition in locally advanced dMMR colon cancer
Fruquintinib: a potential new treatment for patients with refractory mCRC
Second-line avelumab is effective in patients with MSI-H/dMMR mCRC
Upper Gastrointestinal Cancer
Deep learning models predict the risk of relapse and the mutational profile in GIST
Addition of pembrolizumab to lenvatinib does not improve OS in advanced HCC
New, highly selective inhibitor of FGFR2 driver alterations and resistance mutations
Chemo-immunotherapy in gastric cancer is more effective when administered in parallel
Tumour infiltrating lymphocytes identify patients with immunogenic triple-negative breast cancer
OS benefit of abemaciclib in HR-positive/HER2-negative advanced breast cancer not (yet) statistically significant
OS benefit of sacituzumab govitecan in pre-treated HR-positive/HER2-negative metastatic breast cancer
A pathway from air pollution to lung cancer in non-smokers identified
Selective KRASG12C inhibitor sotorasib demonstrates superior PFS and ORR compared to docetaxel in previously treated patients with NSCLC
Promising clinical activity of tepotinib plus osimertinib in NSCLC with MET amplification after progression on first-line osimertinib
High pathological responses in borderline resectable NSCLC patients after induction with dual immunotherapy and concurrent chemoradiotherapy
Treatment with tumour-infiltrating lymphocytes for advanced melanoma outperforms ipilimumab
Neoadjuvant pembrolizumab outperforms adjuvant pembrolizumab in resectable stage III–IV melanomas
Survival-benefit of neoadjuvant T-VEC maintained over 5 years of follow-up
Baseline ctDNA predicts survival in resected stage III–IV melanoma
Genitourinary Cancer – Prostate Cancer
Overall survival benefit of abiraterone in mHSPC is maintained for 7 years
Limited benefit of adding long-term ADT to post-operative radiotherapy in prostate cancer
Intensified ADT benefits biochemical progression-free survival in biochemically relapsed prostate cancer
Genitourinary Cancer – Non-Prostate Cancer
Adjuvant nivolumab plus ipilimumab does not improve survival in patients with localised RCC at high risk of relapse after nephrectomy
Triple therapy improves progression-free survival in patients with advanced RCC versus dual therapy
Adjuvant atezolizumab does not improve outcomes for patients with RCC and increased risk of recurrence
OS benefit for advanced ovarian cancer patients treated with maintenance olaparib
Maintenance tegafur-uracil does not improve survival in locally advanced cervical cancer
Head and Neck Cancer
Adding first-line pembrolizumab to CRT in locally advanced HNSCC does not significantly prolong survival or event-free survival
5-FU-free chemotherapy combination as an alternative for first-line treatment of recurrent or metastatic HNSCC
Epstein Barr virus-specific autologous cytotoxic T lymphocytes do not improve survival in nasopharyngeal carcinoma