ESMO Virtual Congress 2020: Invited Discussant: Abiraterone Acetate plus Prednisolone for Hormone-Naïve Prostate Cancer: Long-Term Results from Metastatic (M1) Patients in the STAMPEDE Randomised Trial

(UroToday.com) In this presentation, Dr. Maria DeSantis reviewed the history of STAMPEDE for context on the data presented in abstract 611O for long term follow-up on outcomes in men with metastatic hormone-sensitive prostate cancer randomized to either standard of care or standard of care plus abiraterone acetate. She first focused on the results of the long-term follow-up, then discussed how these data have been implemented in the real world, then ended with a discussion of how clinical and molecular features may impact treatment selection amongst the multiple agents with efficacy as first-line therapy in metastatic hormone-sensitive prostate cancer.

First, the findings presented to confirm the results initially presented in 2017, that the addition of abiraterone acetate and prednisone extended overall survival in men relative to standard of care alone. The updated hazard ratio for death is similar to that initially published, at 0.60. The median survival for men in the abiraterone acetate arm was 6.6 years, relative to 3.8 in the standard of care arm. Importantly, the benefit for the addition of abiraterone held across patients if stratified by LATITUDE high or low risk, or CHAARTED high or low volume disease.

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Data comparing these outcomes with other trials in the same clinical space were then presented as below.

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The question then emerges, with multiple drugs potentially available to treat patients with metastatic hormone-sensitive prostate cancer, how to choose? One limitation will be cost, as approvals for use vary by regulatory agency. Another decision point will be patient comorbidities and toxicity profile. Third will be quality of life data. Data from ASCO GU in 2020 suggested that the global quality of life was lower, mainly in the first year, with docetaxel relative to abiraterone treatment.  

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Published real-world treatment data suggests that a substantial portion of men with hormone-sensitive metastatic prostate cancer are receiving LHRH-axis therapy alone without the addition of docetaxel, abiraterone, or second-generation androgen receptor inhibitor.

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The covid19 pandemic has also changed the risk/benefit profile of hormone-sensitive prostate cancer treatment. This is especially relevant in the UK, as NICE has not approved abiraterone  reimbursement in high-volume disease.

Ultimately, experts in prostate cancer care continue to debate treatment selection, as illustrated in the below pie chart from the Advanced Prostate Cancer Consensus Conference in 2019, though most experts agree with the addition of some other therapy to ADT in M1 castration-sensitive high-volume metastatic disease. 

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Ultimately, treatment selection may be further impacted beyond clinical characteristics by the identification of molecular factors associated with response. In a publication from this year (Gibson et al JCO Precision Oncology 2020), there were no clear differences in the frequency of mutations as assessed by Foundation Medicine targeted next-generation sequencing between high-volume and low-volume subgroups within STAMPEDE patients. Further work across multiple cohorts may be more informative, although the molecular determinants of response may not be found by DNA sequencing.

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In conclusion, data from Arm G of STAMPEDE with median 6 years of follow-up confirms the survival advantage of adding abiraterone to standard of care. Further delineation of which patients derive the most benefit versus those that may benefit from alternative treatment approaches requires further cooperative research across clinical trial contexts. This work will hopefully be forthcoming in the next few years.

Presented by: Maria De Santis, MD, Medical Oncologist at the Charite Medical University Hospital, Berlin, Germany

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2020 European Society for Medical Oncology Virtual Congress (#ESMO20), September 19th-September 21st, 2020.