e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2020

Systematic review and meta-analysis of treatment related toxicities from second-generation androgen receptor inhibitors in advanced prostate cancer (#228)

Sana Haider 1 2 , Eunice Dai 1 3 4 , Hao Sim 2 5 6 7 8 , Bavanthi Balakrishnar 1 , Joseph Descallar 4 9 , Pei Ding 10 , Wei Chua 1 3 4
  1. Medical Oncology, Liverpool Cancer Therapy Centre, Sydney, NSW, Australia
  2. Medical Oncology, The Kinghorn Cancer Centre, Sydney, NSW, Australia
  3. Western Sydney University, Sydney, NSW, Australia
  4. Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
  5. St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
  6. NHMRC, Clinical Trials Centre, Sydney, NSW, Australia
  7. University of Sydney, Sydney, NSW, Australia
  8. Medical Oncology, Chris O'Brien Lifehouse, Sydney, NSW, Australia
  9. South Western Sydney Clinical School, University of New South Wales, Sydney, NSW , Australia
  10. Medical Oncology, Nepean Hospital, Sydney, NSW, Australia

Introduction:

The novel androgen receptor inhibitors have been shown to be effective in advanced prostate cancer (PCa) in the metastatic castrate-sensitive (CSPC), metastatic castrate-resistant (CRPC) and high-risk, non-metastatic (nmPC) settings. We conducted a study level meta-analysis to explore and compare toxicities from these novel agents which may improve treatment selection.

Methods:

MEDLINE and PubMed databases were searched for randomised controlled trials of apalutamide, darolutamide and enzalutamide using pre-specified keywords, inclusion and exclusion criteria. The risk of toxic death, grade 3 or 4 adverse events (AEs) and treatment discontinuation owing to AEs was analysed using weighted risk ratio (RR) calculations, with corresponding 95% confidence intervals (CI). The most common toxicities identified from the trials and toxicities of interest such as falls and seizures were reviewed. Subgroup analysis was performed to compare between the CSPC, CRPC and nmPC settings.

Results:

Ten trials with a total of 6407 patients were included. Compared to control, there was similar risk of toxic death (RR 1.31, CI 0.81-2.1, p=0.23) and grade 3 or 4 AEs (RR 1.05, CI 0.86-1.27, p=0.6). Treatment discontinuations owing to AEs were reported in 9% (RR 1.25, CI: 1.01-1.55, p=0.04). Fatigue, hypertension, falls and hot flushes were significantly more common, in particular hypertension (RR 1.59, CI: 1.16-2.17, p=0.0091) and falls (RR 1.63, CI 1.21-2.19, p=0.005). The risk of seizures was not increased. Grade 3 or 4 AEs were significantly more common in the nmPC setting (RR 1.28, CI 1.16-1.40, p=0.007).

Conclusions:

The novel anti-androgens appear safe in advanced PCa with no substantive increased risk of toxic death or grade 3 and 4 adverse events. However, toxicities such as falls and hypertension are common, as well as treatment discontinuation owing to AEs. Analysis of specific toxicities of each agent and treatment setting may provide insight into improved treatment selection in the future.