By Gene Emery
(Reuters Health) - 31/5/2019
In men with metastatic, castration-sensitive prostate cancer, adding apalutamide to conventional androgen-deprivation therapy (ADT) produced a 52% increase in the rate of radiographic progression-free survival, in a first interim analysis of the international TITAN study.
After a median follow-up of 22.7 months, the researchers calculated a 24-month progression-free survival rate of 68.2% with apalutamide and 47.5% with placebo therapy in addition to ADT (P<0.001).
"The effect of apalutamide on radiography progression-free survival was consistently favorable across the subgroups analyzed, including previous docetaxel use and both high- and low-volume disease, the researchers said.
Overall survival was 82.4% and 73.5% respectively (P=0.005), reflecting a 33% lower risk of death, with very similar rates of grade 3 or 4 side effects.
"This is a very potent drug. It's surprising to see that magnitude of benefit so early," senior author Dr. Simon Chowdhury, a consultant oncologist in London, told Reuters Health in a telephone interview. "This is really important for our patients and this is a study that benefits a large number of patients."
"We're seeing very meaningful endpoints," he said.
The results were released Friday at the American Society of Clinical Oncology's annual meeting in Chicago and online by the New England Journal of Medicine.
Janssen, a division Johnson & Johnson that sells apalutamide under the brand name Erleada, paid for the study. The company is seeking approval from the U.S. Food and Drug Administration for use of the drug for this type of prostate cancer. Erleada was approved for non-metastatic castration-resistant prostate cancer in February 2018.
Roughly one in four men with prostate cancer present with the type of advanced disease seen in this trial. Their median overall survival is typically less than five years.
Apalutamide treatment was designed to give a more complete blockage of androgen signaling.
All the 1,052 volunteers had adenocarcinoma of the prostate and at least one distant metastasis. They were allowed up to six cycles of docetaxel, and no more than six months of ADT therapy, radiation or surgery for symptoms.
The researchers also found that the drug produced PSA levels that were below detection in 68% of patients compared with 29% in the placebo arm.
The drug did not significantly affect time to pain progression, but Dr. Chowdhury said those data are "a little immature at this stage. My belief is that it will be positive going forward."
Most people who discontinued the trial intervention did so because their disease progressed. Discontinuation rates for progression were 18.9% with apalutamide and 43.1% with placebo.
Eight percent of apalutamide recipients dropped out of the study because of adverse events versus 5.3% getting placebo. An adverse event from treatment was judged to have killed 1.9% of apalutamide patients and 3.0% of placebo patients. There was no clear pattern to those deaths.
Serious rash was about 10 times more common with apalutamide. Mild to moderate hypothyroidism was nearly 6 times more common.
"Adverse events were generally consistent with the known safety profile of apalutamide," the researchers said.
But overall, the toxicity of apalutamide is low, said Dr. Chowdhury. "This is very different from chemotherapy. It's very difficult to pick between placebo and the actual drug. These drugs are well-tolerated, you can give them for a long period of time and patients do very well with them."
"These data suggest that ADT alone should no longer be considered the standard of care for metastatic castration-sensitive prostate cancer," the company's vice president for clinical development in oncology said in a news release.
TITAN is being conducted at 260 sites in 23 countries. The study's volunteers will be followed indefinitely.
N Engl J Med 2019.