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STAMPEDE: No Additional mHSPC Benefit With Enzalutamide

Use of enzalutamide alongside abiraterone plus steroids and androgen deprivation therapy does not further improve overall survival of metastatic hormone-sensitive prostate cancer
12 Sep 2022
Cytotoxic Therapy
Prostate Cancer

Author: By Lynda Williams, Senior medwireNews Reporter 

 

medwireNews: Research shows that the addition of enzalutamide to abiraterone acetate plus prednisolone/prednisone (AAP) and androgen deprivation therapy (ADT) does not improve overall survival (OS) for patients with metastatic hormone-sensitive prostate cancer (mHSPC). 

STAMPEDE investigator Gerhardt Attard, from UCL Cancer Institute in London, UK, presented findings after more than 5 years of follow-up at the ESMO Congress 2022 in Paris, France.  

He reminded delegates that the study initially randomly assigned patients in the AAP trial of 2011–2013 to receive either AAP plus standard of care (ADT, n=501) or standard of care alone (n=502), before later in 2014–2016 assigning a further group of patients to receive standard of care (with or without docetaxel after January 2016, n=454) or enzalutamide alongside AAP and standard of care (n=462). 

The STAMPEDE protocol included patients with one or more bone, pelvic, abdominal or chest metastases and those with no metastases who were either node positive or node negative with two or more high-risk features, or relapsing with high-risk features. 

The patient characteristics were “well balanced across both trials”, Gerhardt Attard commented, with 94% of participants having de novo disease and 6% a relapse after radical therapy.  

At the final data cutoff in July 2022, patients in the initial AAP trial had been followed up for a median 95.8 months and those in the AAP plus enzalutamide arm for 71.7 months. At this time, 23% of patients in the AAP trial were continuing to receive AAP, as were 25% of those in the AAP plus enzalutamide arm. 

There was “clear and significant evidence of an improvement in survival in both trials” with use of AAP with or without enzalutamide versus standard of care, the investigator said, but he added that there was no evidence of an additional improvement in OS with the inclusion of enzalutamide. The significant hazard ratios (HRs) for OS in the AAP trial and AAP plus enzalutamide trial were a comparable 0.62 and 0.65. 

Prespecified subgroup analysis by baseline stratification factors showed an interaction for age (HR=0.52 for age less than 70 years) and for patients who did not regularly use NSAID or aspirin (HR=0.56) in the AAP trial but not in the AAP plus enzalutamide trial. Without any biological explanation for this, “we do not believe this should impact or have an influence on clinical implementation”, commented the presenter. 

After docetaxel use became standard of care, 148 patients randomly assigned to the AAP plus enzalutamide trial were considered for the chemotherapy. Patients with planned use were younger, had a higher Gleason sum and were more likely to have prostate cancer pain than those without. 

Gerhardt Attard said there was no evidence of an interaction between receipt of docetaxel and AAP plus enzalutamide, and that the findings should be interpreted in context of the larger studies of triplet therapy. 

Metastatic progression-free survival was also similar in the AAP trial and AAP plus enzalutamide trial, with significant HRs of 0.50 and 0.52, and again “no evidence of a difference in treatment effect or between-trial heterogeneity”, the presenter said. 

He noted that the addition of enzalutamide to AAP was associated with similar toxicities to that of AAP alone – namely increases in fatigue, liver enzymes and hypertension compared with standard of care. But the presenter emphasized that the adverse events “occurred more frequently” and arose within a shorter time after beginning treatment with AAP plus enzalutamide than with AAP alone. 

Finally, the investigator reported that after 84 months of follow-up of the AAP trial and the final report, 48% of patients given AAP were alive compared with 30% of those who were not.  

While emphasizing that AAP and enzalutamide “should not be combined for mHSPC, nor high-risk localised prostate cancer”, Gerhardt Attard nevertheless concluded that the use of AAP with standard of care maintained “clinically important improvements in OS” after 7 years of follow-up. 

Session discussant Elena Castro Marcos, from Hospital Universitario 12 Octubre in Madrid, Spain, agreed that “novel hormonal therapies in combination do not add to novel hormone therapies in monotherapy”, citing findings from the ACIS, Alliance A031201 and PLATO trials for metastatic castration-resistant disease. 

Reference  

LBA62 - Attard G, Murphy LR, Clarke NW, et al. Comparison of abiraterone acetate and prednisolone (AAP) or combination enzalutamide plus AAP for metastatic hormone sensitive prostate cancer starting androgen deprivation therapy: Overall survival results of 2 randomised phase III trials from the STAMPEDE protocol. Ann Oncol 2022; 33 (suppl_7): S808–S869. Doi: 10.1016/annonc/annonc1089

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

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