Barcelona, Spain (UroToday.com) At the prostate cancer poster discussion at ESMO 2019, Dr. Henrik Gronberg provided a discussion of three important abstracts: the updated STAMPEDE “M1|RT Comparison”, as well as patient reported outcomes from both ENZAMET and TITAN.
Dr. Gronberg notes that in the initial STAMPEDE “M1|RT Comparison” published last year, the STAMPEDE collaborators noted that metastatic burden was a determinant of benefit in a pre-specified directionally hypothesized subgroup analysis, showing that men with low burden of metastatic disease derived a benefit from prostate radiotherapy + standard of care (HR 0.68, 0.52-0.90).1 In the updated analysis, Dr. Gronberg notes that the authors posed to answer the following questions:
- Does prostate radiotherapy + standard of care benefit over standard of care alone in patients with only non-regional lymph node or visceral metastasis? Based on the STAMPEDE data, the answer for only non-regional lymph nodes is yes: In lymph node only patients, prostate radiotherapy improved OS (HR 0.62, 95% CI 0.35-1.09) and FFS (HR 0.64, 95% CI 0.43-0.96). However, for visceral metastasis, the answer is no: OS HR 0.92, 95% CI 0.58 – 1.45; FFS HR 0.88, 95% CI 0.62-1.25.
- Are bone metastasis counts on bone scan predictive of benefit from prostate radiotherapy + standard of care? Yes, prostate radiotherapy + standard of care regardless of anatomic location improves FFS and OS in patients with <= 3 bone metastases, however there is a watershed at 4 bone metastases, and a beneficial effect at >=5 bone metastases is less certain.
- Should patients with >= 4 bone metastases all within the vertebral column and pelvis and no visceral metastasis be considered as low burden? No, based on the new STAMPEDE metastatic burden criteria, high burden disease is >=4 bone metastases regardless of location OR any visceral metastasis.
As highlighted by Dr. Gronberg, both ENZAMET 2 and TITAN 3 had remarkable efficacy results, initially presented at ASCO 2019. He notes that what makes ENZAMET quite remarkable is that 45% of patients also received docetaxel, which during the time of randomization was the new standard of care. For ENZAMET, health-related quality of life was measured with the EORTC QLQ-C30 and PR25 metrics at weeks 0, 4, 12, and then every 12 weeks until clinical progression. Deterioration-free survival was assessed and defined a-priori as the earliest of death, clinical progression, cessation of study treatment, or a 10-point worsening from baseline (minimum clinically important difference on scales scored from 0 to 100) in the pertinent health-related quality of life sub-scale: physical functioning, global health and quality of life, cognitive functioning, and fatigue. The authors found that addition of enzalutamide maintained global health and quality of life and improved deterioration free survival.
In TITAN, patient reported outcomes were assessed using the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and Euro QoL Group EQ-5D-5L. BPI and BFI were completed for 7 consecutive days (day-6 plus day 1 of each cycle visit), then at months 4, 8, and 12 in follow-up. FACT-P and EQ-5D-5L were completed cycle 1 through cycle 7, then every other cycle through end of treatment, and at months 4, 8, and 12 in follow-up. The authors reported that health-related quality of life was preserved with the addition of apalutamide to ADT, did not increase fatigue, and improved time to pain progression, albeit not statistically significant.
Dr. Gronberg noted that following take-home messages/opinions from these two patient reported outcomes studies for mHNPC:
- Men on ADT + enzalutamide or ADT + apalutamide retain their health-related quality of life during treatment
- However, men on ADT + enzalutamide appear to have more fatigue and decrease in physical and cognitive function compared to men on ADT + abiraterone acetate
But, Dr. Gronberg poses the following unanswered questions:
- How sensitive are these instruments in measuring global health-related quality of life?
- If we treat men with metastatic prostate cancer with a new drug should we not expect a better health-related quality of life and not just the same as the standard of care?
- What is the global health-related quality of life in the ENZAMET study in men treated with docetaxel?
- We still do not know who to treat with docetaxel and who to treat with the new anti-androgens
Presented by: Henrik Gronberg, MD, PhD, Professor in Cancer Epidemiology and Senior Physician at the Karolinska Institutet
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2019 European Society for Medical Oncology annual meeting, ESMO 2019 #ESMO19, 27 Sept - 1 Oct 2019 in Barcelona, Spain
- Parker CC, James ND, Brawley CD, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): A randomized controlled phase 3 trial. Lancet 2018 Dec 1;392(10162):2353-2366.
- Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med 2019 Jul 11;381(2):121-131.
- Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med 2019 Jul 4;381(1):13-24.
Further Related Content:
ASCO 2019: ENZAMET, Overall Survival Results of a Phase III Randomized Trial of Standard-of-care Therapy with or without Enzalutamide for mHSPC, an ANZUP-led International Cooperative Group Trial
ASCO 2019: TITAN: Meets Dual Primary Endpoints, Apalutamide vs Placebo in Patients with Metastatic Castration-sensitive Prostate Cancer Receiving ADT
Health-Related Quality Of Life After Apalutamide Treatment In Patients with Metastatic Castration-Sensitive Prostate Cancer (TITAN): A Randomised, Placebo-Controlled, Phase 3 Study