Patients with metastatic castration-resistant prostate cancer (mCRPC) and visceral metastases (liver and lung) fare better with the androgen receptor inhibitor enzalutamide than placebo, according to a new analysis from the phase III AFFIRM trial. There were differences in response based on which of those two sites had metastases, suggesting they should be considered differently for treatment.
“Visceral metastases are identified in approximately 22% to 30% of patients with mCRPC and are associated with unfavorable outcomes,” wrote study authors led by Yohann Loriot, MD, PhD, of Université Paris-Saclay in Villejuif, France.
The AFFIRM trial included 1,199 mCRPC patients who had been previously treated with docetaxel, and showed a significant reduction in the risk of death compared to placebo. The new analysis focused only on AFFIRM patients with visceral metastases; of a total of 278 patients, 97 (34.9%) had liver metastases, 152 (54.7%) had lung lesions, and 29 patients (10.4%) had both of the two and were included in the liver subgroup. The results were published online ahead of print in Cancer.
For patients with liver metastases, those receiving enzalutamide had a median overall survival of 9 months, compared with 5.7 months with placebo (hazard ratio [HR], 0.697 [95% CI, 0.436–1.114]). For lung metastases, overall survival was 17 months and 15.8 months, respectively (HR, 0.848 [95% CI, 0.510–1.410]). The 12-month overall survival rate was better with enzalutamide, at 37.7% compared with 20.6% with placebo in liver metastases patients; for lung metastases, those rates were 65.1% and 55.3%, respectively.
The median radiographic progression-free survival time was 2.9 months with enzalutamide and 2.8 months with placebo in liver metastases patients (HR, 0.645 [95% CI, 0.413–1.008]); the difference was more stark in lung metastases patients, at 13.9 months with enzalutamide and 5.3 months with placebo (HR, 0.386 [95% CI, 0.259–0.577]). The 12-month progression-free survival rate in liver metastases patients was 11.6% with the study drug and 3% with placebo; in lung metastases patients, these rates were 30.9% and 8.2%, respectively.
Progression-free survival response, defined as a decline of at least 50%, was also much better with enzalutamide. In liver metastases patients, 35.1% of those receiving enzalutamide and only 4.8% of those receiving placebo had a PSA response; for lung metastases patients, the rates were 52.1% and 4.9%, respectively.
Almost all patients in both groups developed at least one treatment-emergent adverse event of any grade. There was no difference, however, between patients with visceral or non-visceral metastases with regard to toxicity.
“These data strongly suggest that patients who present with visceral metastases in liver vs lung should be assessed independently given the differential prognosis and response to treatment observed based on the site of visceral disease,” the authors concluded, adding that visceral metastases generally should not be used as an exclusion criteria in trials, since benefit is still clearly derived from the treatment.