Metformin Active Surveillance Trial in Low-Risk Prostate Cancer
Metformin did not significantly reduce the risk of disease progression compared with active surveillance in patients with low-risk prostate cancer.
Improved Survival with Enzalutamide in Biochemically Recurrent Prostate Cancer
Author(s): Neal D. Shore, M.D.1; Murilo de Almeida Luz, M.D.2; Ugo De Giorgi, M.D., Ph.D.3; Martin Gleave, M.D.4; Geoffrey T. Gotto, M.D., M.P.H.5; Christopher M. Pieczonka, M.D.6; Gabriel P. Haas, M.D.7; Choung-Soo Kim, M.D.8; Miguel Ramirez-Backhaus, M.D.9; Antti Rannikko, M.D., Ph.D.10,11; Matko Kalac, M.D., Ph.D.12; Swetha Sridharan, M.B., B.S.13; Matt Rosales, Ph.D.7; Yiyun Tang, Ph.D.14; Ronald F. Tutrone, Jr., M.D.15; Balaji Venugopal, M.B., B.S., M.D.16,17; Arnauld Villers, M.D., Ph.D.18; Henry H. Woo, M.B., B.S., D.Med.Sc.19,20; Fong Wang, M.D., Ph.D.14; Stephen J. Freedland, M.D.21,22;
Source: DOI: 10.1056/NEJMoa2510310
Dr. Maen Hussein's Thoughts
Overall survival was 78.9% in the combination group compared with 69.5% in the leuprolide-alone group (HR 0.60). Enzalutamide monotherapy resulted in an overall survival of 73.1%, which was not statistically significant. We were already aware of the progression-free survival benefit; now we have overall survival data. This case was also presented in the MOC questions, where the correct answer was to add enzalutamide for a patient with a rising PSA on an LHRH agonist without imaging evidence of disease.
BACKGROUND
In the phase 3 EMBARK trial, enzalutamide plus leuprolide and enzalutamide monotherapy were associated with longer metastasis-free survival than leuprolide alone among patients with biochemically recurrent prostate cancer. The final analysis of overall survival has not been reported.
METHODS
We randomly assigned patients with prostate cancer who had high-risk biochemical recurrence in a 1:1:1 ratio to receive enzalutamide plus leuprolide (the combination group), leuprolide alone (the leuprolide-alone group), or enzalutamide monotherapy (the monotherapy group). The primary end point was metastasis-free survival, assessed in the combination group as compared with the leuprolide-alone group. Overall survival was an alpha-controlled, key secondary end point. Updated results for prespecified secondary end points, including the time to first use of new antineoplastic therapy and the time to the first symptomatic skeletal event, were summarized descriptively, as was progression-free survival with the first subsequent therapy, an exploratory end point. Research Summary Enzalutamide in Biochemically Recurrent Prostate Cancer
RESULTS
The 8-year overall survival was 78.9% (95% confidence interval [CI], 73.9 to 83.1) in the combination group and 69.5% (95% CI, 64.0 to 74.3) in the leuprolide-alone group; the hazard ratio for death was 0.60 (95% CI, 0.44 to 0.80; P
CONCLUSIONS
Overall survival was significantly longer with the combination of enzalutamide and leuprolide than with leuprolide alone among patients with prostate cancer with high-risk biochemical recurrence. Enzalutamide monotherapy was not superior to leuprolide alone in the analysis of overall survival. (Funded by Pfizer and Astellas Pharma; EMBARK ClinicalTrials.gov number, NCT02319837.)
Author Affiliations
1START Carolinas, Myrtle Beach, SC; 2Division of Urologic Oncology, Erasto Gaertner Hospital, Curitiba, Brazil; 3Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori, Meldola, Italy; 4Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; 5Southern Alberta Institute of Urology, University of Calgary, Calgary, Canada; 6Clinical Research, U.S. Urology Partners and Associated Medical Professionals of New York, Syracuse; 7Oncology Global Development, Astellas Pharma, Northbrook, IL; 8Department of Urology, Ewha Womans University Mokdong Hospital, Seoul, South Korea; 9Servicio de Urología, Fundación Instituto Valenciano de Oncología, Valencia, Spain; 10Department of Urology and Research Program in Systems Oncology, University of Helsinki, Helsinki; 11Helsinki University Hospital, Helsinki; 12Oncology Division, Pfizer, New York; 13Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia; 14Oncology Division, Pfizer, South San Francisco, CA; 15Chesapeake Urology Research Associates, Towson, MD; 16Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, United Kingdom; 17University of Glasgow, Glasgow, United Kingdom; 18Department of Urology, University of Lille, Claude Huriez Hospital, Centre Hospitalier Universitaire Lille, Lille, France; 19Department of Urology, Blacktown and Mount Druitt Hospitals, Blacktown, NSW, Australia; 20Department of Uro-Oncology, Chris O’Brien Lifehouse, Camperdown, NSW, Australia; 21Department of Urology, Samuel Oschin Comprehensive Cancer Institute, Cedars–Sinai Medical Center, Los Angeles; 22Durham Veterans Affairs Administration Medical Center, Durham, NCRelated Articles
177Lu-Prostate-Specific Membrane Antigen Neoadjuvant to Stereotactic Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR): An Open-Label, Randomized, Controlled, Phase II Study
For our radiation oncology colleagues, the addition of PSMA-directed therapy prior to stereotactic body radiation therapy (SBRT) improved progression-free survival (PFS) in patients with oligometastatic prostate cancer. Two cycles of PSMA-directed therapy were administered before SBRT.
Development and Validation of an Artificial Intelligence Digital Pathology Biomarker to Predict Benefit of Long-Term Hormonal Therapy and Radiotherapy in Men With High-Risk Prostate Cancer Across Multiple Phase III Trials
A new MMAI-derived digital pathology biomarker was trained and prospectively validated across multiple NRG/RTOG phase III trials, including RTOG 9202 (N=1,192), to predict which high-risk/locally advanced PCa patients benefit from LT-ADT vs ST-ADT with RT. In the overall cohort, LT-ADT reduced DM (17% vs 26% at 15 years) and DDM (15% vs 23% at 15 years), but this benefit was limited to biomarker-positive patients (DM: 19% vs 33%; DDM: 19% vs 30%), with no advantage seen in biomarker-negative patients (DM: 11% vs 11%; DDM: 9% vs 10%). This tool could allow about a third of our "high-risk" patients to avoid two extra years of ADT without compromising metastasis outcomes, while ensuring we intensify for those most likely to benefit. In short, this is a practical step toward personalizing ADT duration and sparing toxicity for a significant subset of our patients.
European Study of Prostate Cancer Screening — 23-Year Follow-up
A 13% reduction in mortality was observed in the screening group, with an improved harm-benefit ratio. For every 456 men screened, one prostate cancer death was prevented. It is an easy and inexpensive test, though concerns remain regarding unnecessary biopsies and overtreatment.
Pasritamig, a First-in-Class, Bispecific T-Cell Engager Targeting Human Kallikrein 2, in Metastatic Castration-Resistant Prostate Cancer: A Phase I Study
Pasritamig was administered to patients who had received a median of four prior lines of systemic therapy. It was well tolerated, with manageable adverse events, making it suitable for outpatient administration. The treatment showed a median radiographic progression-free survival of 7.85 months, and 14 out of 33 participants achieved a ≥50% reduction in baseline PSA levels. So, stay tuned.