Abstract
PurposeThis study was undertaken to determine the safety and efficacy of fexapotide triflutate (FT) 2.5 mg and 15 mg for the treatment of Grade Group 1 prostate cancer.MethodsProspective randomized transrectal intraprostatic single injection FT 2.5 mg (n = 49), FT 15 mg (n = 48) and control active surveillance (AS) (n = 49) groups were compared in 146 patients at 28 U.S. sites, with elective AS crossover (n = 18) to FT after first follow-up biopsy at 45 days. Patients were followed for 5 years including biopsies (baseline, 45 days, and 18, 36, and 54 months thereafter), and urological evaluations with PSA every 6 months. Patients with Gleason grade increase or who elected surgical or radiotherapeutic intervention exited the study and were cumulatively included in the data analysis. Percentage of normal biopsies in baseline focus quadrant, tumor grades, and volumes; and outcomes including Gleason grade in entire prostate as well as treated prostate lobe, interventions associated with Gleason grade increase and total incidence of interventions were assessed.ResultsSignificantly improved long-term clinical outcomes were found after 4-year follow-up, with percentages of patients progressing to interventions with and without Gleason grade increase significantly reduced by FT single treatment. Results in the FT 15-mg group were superior to the FT 2.5-mg dose group. There were no drug-related serious adverse events (SAEs).ConclusionsFT showed statistically significant long-term efficacy in the treatment of Grade Group 1 patients regarding clinical and pathological progression. FT 15 mg showed superior results to FT 2.5 mg. There were no drug-related SAEs; FT injection was well tolerated.
Highlights
fexapotide triflutate (FT) is supplied as a sterile lyophilized powder that is reconstituted in 10-mL sterile phosphate buffered saline and injected into prostate by the transrectal route under transrectal ultrasound (TRUS) guidance by standard technique using a conventional #22 gauge sterile needle
Prior to the 18-month biopsy assessment n = 14 (9.6%) of subjects had exited the study due to pathological progression of their prostate cancer (PCa) and n = 11 (7.5%) exited without progression due to the decision to receive interventions such as surgery or radiotherapy for their PCa, with 5 (3.4%) patients lost to follow-up (LTFU) and 32 (21%) withdrew consent without documented progression of their PCa
Clinical progression after 4 years was reduced by FT whether calculated by occurrence of interventions for PCa with increased Gleason grade in overall prostate (− 73.3% for FT 15-mg group compared to active surveillance (AS), − 62.6% for pooled FT groups); or by interventions with or without Gleason increase (− 54.7% for FT 15-mg group compared to AS; − 41.5% for pooled FT groups)
Summary
There is an unmet need for treatments for low-grade prostate cancer (PCa) that produce minimal collateral tissue damage and unintended sexual, urinary, and bowel function side effects [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23]. Grade groups were first proposed by authors at Johns Hopkins Hospital led by Dr Epstein [21], validated in a large multi-institutional study [22], and subsequently endorsed by the 2014 International Society of Urological Pathology Consensus Conference [23] and the WHO. Gleason Grade Group 1 is the most commonly diagnosed PCa and is considered very low-to-low risk by the National Comprehensive Cancer Network (NCCN) criteria. These cancers, albeit low risk, are still infrequently capable of biologic progression, and cause ongoing patient anxiety. Often, these low-risk cancer patients may still receive interventional therapies which can result in urinary, bowel, and sexual side effects. Agree that more pragmatic parameters of objective clinical and pathological progression are currently the most realistic approach to assessment of efficacy and safety [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]
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