(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium featured a prostate cancer session and a presentation by Dr. Alicia Morgans discussing the interaction of age and benefit of treatment intensification in advanced prostate cancer. Treatment intensification for men with advanced prostate cancer consistently demonstrates improvements in overall survival when compared to ADT alone. However, treatment intensification increases morbidity and may contribute to worsening other-cause mortality. At the GU ASCO 2024 annual meeting, Dr. Morgans and colleagues aimed to determine if there is an interaction of age and treatment intensification on overall survival in men with advanced prostate cancer.
This study included a systematic literature search in MEDLINE, Embase, and conference proceedings that were searched to identify contemporary randomized phase 3 trials in advanced prostate cancer evaluating the role of treatment intensification with chemotherapy and/or androgen receptor-signaling inhibition between January 1, 2010, through September 1, 2023. Trials in metastatic hormone-sensitive prostate cancer (mHSPC) and non-metastatic castration-resistant prostate cancer (nmCRPC) were included given potential for competing risks. Of note, mCRPC trials were excluded. Meta-analyses were performed with random-effect modeling, and meta-regression was performed using Hartung-Knapp methods in mHSPC trials accounting for drug (docetaxel, abiraterone acetate/prednisone, non-abiraterone acetate/prednisone androgen receptor-signaling inhibitors (apalutamide, enzalutamide, or darolutamide)), use of radiotherapy to the primary, percent high volume disease, percent synchronous metastatic disease, and median PSA. Age was dichotomized as < or ≥ 70 years in 8 trials, and < or ≥ 65 years in 6 trials.
There were 14 trials with 16 randomized comparisons (n = 17,765 patients) included. A total of 9,229 younger and 7,458 older men were included in age-specific analyses. Overall, treatment intensification significantly improved overall survival (HR 0.72, 95%CI 0.69-0.76, p<0.0001), which was consistent irrespective of disease state:
- mHSPC HR 0.72, 95% CI 0.78-0.77
- nmCRPC HR 0.74, 95% CI 0.66-0.83
There was a significant interaction between age and treatment intensification on overall survival (p-interaction <0.001):
As such, treatment intensification in younger men significantly improved overall survival (HR 0.65, 95%CI 0.59-0.72, p < 0.0001), whereas older men derived less benefit from treatment intensification, but treatment intensification did improve overall survival (HR 0.80, 95%CI 0.74-0.87, p < 0001). In a subgroup of older men in mHSPC trials, a significant treatment effect difference based on drug class was observed (p = 0.047):
- Abiraterone acetate/prednisone: HR 0.92, 95% CI 0.77-1.10, p = 0.38
- Docetaxel: HR 0.86, 95% CI 0.70-1.05, p = 0.13
- Non-abiraterone abiraterone acetate/prednisone androgen receptor-signaling inhibitors: HR 0.71, 95% CI 0.63-0.81, p < 0.001
On meta-regression of mHSPC trials, age remained an independent variable associated with treatment intensification benefit (p = 0.005). Key limitations of this study included the post-hoc nature of this aggregate meta-analysis and the use of dichotomized age.
Dr. Morgans concluded her presentation by discussing the interaction of age and the benefit of treatment intensification in advanced prostate cancer with the following take-home points:
- In men with mHSPC and nmCRPC, older age (>= 70 years) was associated with significantly reduced survival benefit from treatment intensification compared to younger age
- This observation appears to potentially driven by drug class: treatment intensification in older men with abiraterone and/or docetaxel had minimal survival benefit, while treatment intensification in older men with non-abiraterone androgen receptor-signaling inhibitors derived significant survival benefits
- Further work leveraging individual patient data is needed to understand the drivers of this observation, including impact of treatment compliance, comorbid conditions, adrenal suppression, outcomes in different prognostic groups, and competing risks in older patients
Presented by: Alicia K. Morgans, MD, MPH, Dana-Farber Cancer Institute, Boston, MA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024