In recent international and local congresses, experts shared the first trial result for optimal ADT duration for PCa patients receiving post-operative RT following RP and ARCHES post-hoc analysis of treatment outcomes in mHSPC patients previously treated with ADT, grouped by post-ADT PSA levels. In addition, insights in optimizing mHSPC treatment strategies were shared with recent evidence.

In recent international and local congresses, experts shared the first trial result for optimal ADT duration for PCa patients receiving post-operative RT following RP and ARCHES post-hoc analysis of treatment outcomes in mHSPC patients previously treated with ADT, grouped by post-ADT PSA levels. In addition, insights in optimizing mHSPC treatment strategies were shared with recent evidence.

ESMO 2022 Presidential Symposium: What is the optimal duration of ADT with post-operative RT?

Prof. Chris Parker from the Royal Marsden Hospital (UK) presented the first result of the RADICALS-HD trial evaluating the effect of ADT duration on MFS among men with PCa receiving post-operative RT following RP.1 Key exclusion criteria included patients with prior pelvic RT, prior hormonal therapy, metastatic disease or a PSA >5 ng/mL.1 Patients were randomized to either no ADT (“None”), 6-month ADT (“Short”) or 24-month ADT (“Long”) following RP, but prior to initiating RT.1 In the None-vs-Short comparison, short ADT did not meaningfully improve MFS compared with no ADT (Figure 1A).1 Similarly, OS (HR, 0.88; 95% CI: 0.65–1.19) and freedom from distant metastasis (HR, 0.82; 95% CI: 0.58–1.15) were not improved but the time to salvage ADT was delayed (HR, 0.54; 95% CI: 0.42–0.70) (Figure 1B).1 Pre-planned subgroup analyses failed to demonstrate any significant effect modification according to pre-RT PSA, comorbidity or randomization stratification factors.1
Figure 1. MFS (A) and time to salvage hormone therapy (B) in None-vs-Short comparison1a

In the comparison of Long-vs-Short, 24-month (long) ADT improved MFS (Figure 2), freedom from distant metastasis (HR, 0.63; 95% CI:0.47–0.85) and delayed the time to salvage ADT (HR, 0.73; 95% CI: 0.59–0.91) compared with 6-month (short) ADT.1 No difference was observed in OS (HR, 0.88; 95% CI: 0.66–1.17).

A statistically significantly greater benefit in MFS was seen in patients with Gleason score of 7 or less in pre-planned subgroup analyses (Table 1).1

The incidence of AEs was not significantly different between treatment groups in the RADICALS-HD trial (Table 2).1 The most common grade 3/4 AEs reported within 24 months of randomization were urethral stricture (6%) and haematuria (4%).1

Table 2. AEs reported within 24 months of trial randomization1
Meaningful improvements were reported with long ADT (24 months) compared with short ADT (6 months) without increasing the risk of AEs1

ARCHES Post-hoc Analysis in ESMO 2022: What are treatment outcomes with Xtandi® in mHSPC patients with prior ADT by baseline PSA levels?

Prof. Daniel Petrylak from the Yale Cancer Center (USA) presented a post-hoc analysis of the ARCHES trial to evaluate the efficacy of Xtandi® + ADT over ADT alone by baseline PSA category.2 Patients who received prior ADT were categorized into three groups using available baseline PSA values – PSA ≤2 ng/mL (12.8%), >2–4 ng/mL (35.5%) and >4 ng/mL (51.7%).2 31.3% of patients initially in the placebo arm crossed over to receive Xtandi® + ADT in the open label-extension following the primary analysis.2 Treatment intensification with Xtandi® produced durable and consistent clinical benefits in rPFS (Figure 3), OS (Figure 4) and other secondary endpoints, irrespective of post-ADT PSA levels prior to initiation.2

Figure 3. rPFS outcomes in patients with prior ADT use for Xtandi® + ADT vs placebo + ADT in baseline PSA categories2

When adjusted for crossover, the rPFS benefit (HR; 95% CI) was more noticeable across the ≤2 ng/mL (0.33; 0.10–0.67), >2–4 ng/mL (0.47; 0.30–0.69) and >4 ng/mL (0.69; 0.51–0.90) baseline PSA subgroups.2

Figure 4. Kaplan-Meier plots of OS adjusted for crossover in patients with prior ADT and
baseline PSA levels ≤0.2 ng/mL (A), >0.2−4 ng/mL (B) and >4 ng/mL (ITT population; C)2a
  • In the >0.2–4 ng/mL baseline PSA group, 88.5% of patients receiving Xtandii® + ADT achieved undetectable PSA levels compared with 22.0% of patients receiving placebo + ADT.2
  • Of the patients with a higher baseline PSA level (>4 ng/mL), 62.5 % of those receiving Xtandi® + ADT achieved undetectable PSA levels compared with 4.3% of patients receiving placebo + ADT.2
Xtandi® + ADT demonstrated a therapeutic role in mHSPC management, regardless of baseline PSA levels post ADT22
Scientific Discussion at the HKCR ASM: How can recent evidence inform the optimal mHSPC treatment strategy?
Prof. Ravindran Kanesvaran from the National Cancer Centre (Singapore) shared his insights in mHSPC treatment selection in combinatorial therapies at the 2022 ASM of the HKCR.3
Figure 5. Factors to consider when choosing an ARSI among mHSPC combinatorial therapies
With proven clinical benefits demonstrated by ARSI doublet combinations, patients’ co-morbidities such as diabetes and heart failure, anticipated treatment toxicity, compliance and cost-effectiveness are consideration factors to optimize the ARSI selection (Figure 5).

When considering selection of doublet vs triplet therapy strategy, Prof. Kanesvaran highlighted these key factors to consider3:
Abbreviations: ADT, androgen deprivation therapy; AE, adverse event; ARSI, androgen receptor signalling inhibitor; ASM, Annual Scientific Meeting; CI, confidence interval; ESMO, European Society for Medical Oncology; HKCR, Hong Kong College of Radiologists; HR, hazard ratio; ITT, intention-to-treat; LHRH, leutinizing hormone-releasing hormone; MFS, metastasis-free survival;mHSPC, metastatic hormone-sensitive prostate cancer; NE, not estimable; NR, not reached; OS, overall survival; PCa, prostate cancer; PSA, prostate-specific antigen; RP, radical prostatectomy; rPFS, radiographic progression-free survival; RT, radiotherapy.

References:
  1. Parker C. Duration of androgen deprivation therapy (ADT) with post-operative radiotherapy (RT) for prostate cancer: first results of the RADICALS-HD trial. Presented at: European Society of Medical Oncology Congress; 9-13 September, 2022; Paris, France.
  2. Petrylak D, Azad AA, Szmulewitz RZ, et al. Overall survival in patients with metastatic hormone-sensitive prostate cancer who received prior androgen deprivation therapy and reached low prostate-specific antigen levels treated further with enzalutamide: Post-hoc analyses of ARCHES. Presented at: European Society of Medical Oncology Congress; 9-13 September, 2022; Paris, France.
  3. Kanesvaran R. Optimizing mHSPC management with latest therapeutic advancement. Presented at: 30th Annual Scientific Meeting of the Hong Kong College of Radiologists; 12-13 November 2022; Hong Kong.

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