Researchers reported promising safety data from an ongoing phase Ib/II clinical trial for SM-88, an investigational combination therapy that might one day offer an alternative to androgen deprivation therapy (ADT) for men with recurrent, nonmetastatic prostate cancer. The findings were presented (abstract 175) at the 2018 Genitourinary Cancers Symposium, held February 8–10 in San Francisco.
“Toxicities typically associated with ADT have not been seen with SM-88, which suggest that ADT may be avoided or delayed without progression in patients with nonmetastatic prostate cancer,” said lead study author Mack Roach, MD, of the University of California San Francisco in a press release.
“Weight loss, osteoporosis, EKG, mean arterial pressure, glucose, and hematocrit were not significantly affected while on SM-88,” reported Roach and coauthors in their poster presentation. There were also no SM-88–related serious adverse events. All of the patients in the study reported maintained or improved interest in sex.
After local therapies fail and nonmetastatic prostate cancer recurs, most patients undergo ADT, which can impact their quality of life. The survival benefits of ADT remain unclear, according to the authors.
Healthy cells produce metabolic energy through mitochondrial oxidative phosphorylation, but most cancer cells generate energy through glycolysis and lactic acid fermentation. SM-88 is a novel, experimental combination treatment consisting of an amino acid analogue, a CYP3a4 inducer, an mTOR inhibitor, and a catalyst that together have been associated with a reduction in circulating tumor cell (CTC) levels.
The research team’s prospective, ongoing study of SM-88 enrolled 19 men with recurrent nonmetastatic prostate cancer, rising prostate-specific antigen (PSA) levels, and detectable CTC levels between September 2016 and December 2017. Thirteen patients were evaluable, having completed more than 1 cycle of the experimental treatment.
Overall, 62% of patients had a grade 1/2 adverse event, but there were no drug-related serious adverse events. Mental function and intimacy were stable and most patients (62%) did not report experiencing hot flashes. CTC and PSA levels were “encouraging”; 57% of patients had more than a 50% reduction in CTCs. Median time to undetectable CTCs was 20 weeks (range, 3–28 weeks). Twelve patients (92%) had at least 1 cycle with decreased PSA, and with a median of 10 months since SM-88 initiation, twelve patients (92%) maintained radiographic progression-free survival.
The findings support evidence from other studies that CTCs might represent a superior prognostic marker to PSA levels, particularly in early recurrent prostate cancer where PSA levels may be affected by factors unrelated to tumor growth, the authors noted.
“This non-toxic treatment may be useful in patients with nonmetastatic prostate cancer and questions the necessity of chemical castration to control nonmetastatic prostate cancer,” the researchers wrote.
The ongoing trial will be completed in late 2018 and the authors hope to then design a pivotal, randomized, controlled phase III trial. If the phase Ib/II and anticipated phase III trials demonstrate SM-88’s safety and efficacy, it could provide an intermediate option between the current choices of observation and ADT for men with recurrent nonmetastatic prostate cancer, according to the authors.