(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between January 25th and 27th was host to a prostate cancer poster session. Dr. Edwin Posadas presented the initial results of STEEL (RTOG 3506), which evaluated treatment intensification with enzalutamide addition to androgen deprivation therapy (ADT) in the setting of salvage radiotherapy for high-risk patients with biochemical relapse following radical prostatectomy.
There is solid evidence that the addition of ADT to radiotherapy in the salvage setting for post-radical prostatectomy, high-risk, biochemically recurrent patients is associated with improved oncologic outcomes, as demonstrated by the DADSPORT (Duration of Androgen Suppression with Post-Operative Radiotherapy) meta-analysis of trials evaluating ADT use with post-operative radiotherapy (RG/RTOG 9601, GETUG-AFU 16, NRG/RTOG 0534, and RADICALS-HD), presented at ESMO 2022. Given the emerging evidence for early androgen receptor pathway inhibitor (ARPI) use in the early biochemically recurrent setting (e.g., EMBARK1), the investigators hypothesized that intensification of androgen receptor blockade with enzalutamide would improve salvage radiotherapy outcomes for high-risk patients.
STEEL (RTOG 3506) is a phase II trial included post-prostatectomy prostate cancer patients who had biochemical recurrence, defined as PSA ≥ 0.2 ng/mL, with ≥1 high-risk feature:
- Gleason 8 – 10
- Seminal vesicle invasion
- pN1
- Persistent PSA >0.1 ng/ml following radical prostatectomy
- PSA ≥0.7 ng/ml
Patients were randomized 1:1 to 24 months of ADT with an LHRH analog or ‘intensified ADT’ with enzalutamide + LHRH analog. Of note, all patients planned for prostatic fossa and pelvic salvage radiotherapy. Para-aortic radiotherapy and lymph node and prostatic fossa lesion radiotherapy boosts were left at the discretion of the radiation oncologist.
The primary study outcome was progression-free survival (PFS), defined as PSA ≥ 0.05 ng/mL or initiation of new therapy following salvage radiotherapy. This study was designed with a target sample size of 170 patients, providing 80% power to detect a hazard ratio (HR) of 0.65 using a one-sided log-rank test with a type 1 error (false negative) rate of 10%
Between April 2019 and August 2022, 188 patients were enrolled. The patient characteristics were well balanced between the two arms. The median patient age was 64 years. Nodal involvement (pN1), pT3a-b, and Gleason 9 disease were noted in 22%, 77%, and 52% of patients, respectively. Over 70% had > 1 aggressive feature. At the time of reporting, the median follow-up duration was 16 months.
With regards to the primary outcome of PFS, there appeared to be a non-significant benefit for intensification with enzalutamide (HR: 0.72, 80% CI: 0.56 to 0.94, p=0.14). Similarly, time to biochemical failure was non-significantly improved in the enzalutamide treated patients (HR: 0.73, 95% CI: 0.50 to 1.09).
Grade 3 and 4 treatment-related adverse events were more common in the enzalutamide arms (23% versus 11%, HR: 1.55, 95% CI: 0.90 to 2.67; 4% versus 1%, respectively The most common adverse events (all grades, >15%) included hot flashes, fatigue, diarrhea, and decreased lymphocytes. The grade ≥3 adverse events (>3%) included decreased lymphocytes and hypertension. The largest differences (>7%) in adverse events included insomnia and decreased lymphocytes. Notably, diarrhea was observed less frequently with enzalutamide (40% versus 54%).
Dr. Posadas concluded that the addition of enzalutamide to standard ADT did not meaningfully increase toxicity. While there was a trend toward a PFS benefit with intensification, this benefit has not yet met statistical significance. Updates on PFS and other clinical endpoints, including quality of life, will be reported with longer follow-up.
Presented by: Edwin Melencio Posadas, MD, FACP, Associate Professor of Medicine, Medical Director, Urologic Oncology Program, Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024
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