Clinical and immunologic impact of short-course enzalutamide alone and with immunotherapy in non-metastatic castration sensitive prostate cancer

Autor: William L. Dahut, Ravi A. Madan, Cindy H. Chau, William D. Figg, Moniquea Williams, Amy Hankin, Sarah E Lochrin, Jennifer L. Marte, James L. Gulley, Renee N. Donahue, Marc R. Theoret, Fatima Karzai, Inger I Rosner, Anna Couvillon, Helen Owens, Harpreet Singh, Munjid Al-Harthy, Lisa M. Cordes, Seth M. Steinberg, Jeffrey Schlom, Philip M. Arlen, Marijo Bilusic
Rok vydání: 2021
Předmět:
Male
Oncology
Cancer Research
Time Factors
medicine.medical_treatment
prostatic neoplasms
Metastasis
killer cells
Androgen deprivation therapy
chemistry.chemical_compound
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Tumor Microenvironment
Immunology and Allergy
Testosterone
030212 general & internal medicine
RC254-282
Prostvac
Aged
80 and over
Clinical/Translational Cancer Immunotherapy
Standard treatment
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Middle Aged
Prostatic Neoplasms
Castration-Resistant
Treatment Outcome
030220 oncology & carcinogenesis
Benzamides
Molecular Medicine
Kallikreins
immunotherapy
medicine.medical_specialty
Immunology
Cancer Vaccines
Drug Administration Schedule
03 medical and health sciences
Internal medicine
Nitriles
Phenylthiohydantoin
medicine
Humans
Enzalutamide
Adverse effect
Aged
natural
Pharmacology
Maryland
business.industry
Immunotherapy
Prostate-Specific Antigen
myeloid-derived suppressor cells
medicine.disease
chemistry
business
Zdroj: Journal for ImmunoTherapy of Cancer, Vol 9, Iss 3 (2021)
Journal for Immunotherapy of Cancer
ISSN: 2051-1426
Popis: BackgroundThe standard treatment for non-metastatic castration sensitive prostate cancer (nmCSPC) is androgen deprivation therapy (ADT) or surveillance. This study evaluated the potential synergy of immunotherapy and enzalutamide (without ADT) in nmCSPC. In addition, the immunologic impact of enzalutamide was also evaluated in men with normal testosterone.MethodsPatients with rising prostate-specific antigen (PSA) after definitive therapy, normal testosterone and no radiographic metastasis were randomized to enzalutamide for 3 months with/without PROSTVAC for 6 months. Thereafter, patients could be retreated with another 3 month course of enzalutamide when PSA returned to baseline. Immune profiles were evaluated in these patients.ResultsThirty-eight patients were randomized with a median PSA=4.38 ng/dL and PSA doubling time=4.1 months. No difference was observed between the two groups for PSA growth kinetics, but PSA responses to enzalutamide were noteworthy regardless of PROSTVAC. The median PSA decline after short-course enzalutamide without ADT/testosterone lowering therapy was 99% in both courses. The median time to PSA recovery to baseline after each 84-day course of enzalutamide was also noteworthy because of the duration of response after enzalutamide was discontinued. After the first and second 3 month cycle of enzalutamide, PSA recovery to baseline took a median 224 (range 84–1246) and 189 days (78–400), respectively. The most common adverse events related to the enzalutamide were grade 1 fatigue (71%) and grade 1 breast pain/nipple tenderness (81%). The only grade 3 toxicity was aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation in two patients. Enzalutamide was independently associated with immune changes, increasing natural killer cells, naïve-T cells, and decreasing myeloid-derived suppressor cells.ConclusionsThree months of enzalutamide without ADT induced substantial PSA control beyond the treatment period and was repeatable, perhaps representing an alternative to intermittent ADT in nmCSPC. In addition, enzalutamide was associated with immune changes that could be relevant as future immune combinations are developed.Trail registration numberclinicaltrials.gov (NCT01875250).
Databáze: OpenAIRE
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