Apalutamide equally beneficial in Asians with nmCRPC
Apalutamide, added to standard treatment with androgen deprivation therapy (ADT), provides comparable clinical benefits among Asian vs non-Asian patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), according to a subset analysis of the phase III SPARTAN study.
Similar with outcomes in non-Asian patients, treatment with apalutamide reduced the risk for distant metastasis (new bone or soft tissue lesions or enlarged lymph nodes outside the pelvis) or death due to any cause by 71 percent (hazard ratio [HR], 0.29; p<0.001) in Asian patients. [ESMO Asia 2018, abstract MOS-2130]
“SPARTAN showed that Asians or non-Asians, there was a hazard ratio benefit,” said lead investigator Prof Paul Mainwaring from the Centre for Personalized Nanomedicine, University of Queensland, Brisbane, Australia. “The high-risk baseline characteristic in Asian patients didn’t affect the benefit of this drug. On top of that, we’ve got a tolerable safety profile that we’re happy to use it in the clinic.”
The Asian patients (9.8 percent of the total SPARTAN population) were from Japan, Taiwan, and South Korea. Most baseline characteristics were similar between Asians and non-Asians. But what was important was that Asian men had a higher proportion of N1 disease and Gleason score was >7. Median time from diagnosis to treatment and median treatment duration were shorter for Asian men. Rates of treatment discontinuation and adverse events were higher.
“These are patients at a very high risk … But the good point was that the benefit of adding apalutamide to ADT over placebo plus ADT was stunning at an HR of <0.3. This was a real revolution and change in the natural history of the disease,” commented Mainwaring. “Imagine if we could give this therapy earlier into these men diagnosed to have a high-risk disease and a PSA doubling time of ≤10 months but no evidence of metastatic disease.”
Looking at the subgroup analysis, the benefits were consistent regardless of patients’ age, number of prior hormone therapy, baseline PSA, ECOG status, bone sparing agent used, and locoregional disease.
In terms of safety, there were no significant differences in treatment-emergent adverse events (TEAEs) between groups, except for skin rash (38 percent in Asians vs 22 percent in non-Asians), which was higher particularly in Japanese men.
“When we looked into that, what we found was that the Asian men who got rash stopped treatment,” revealed Mainwaring. “What we normally do is stop the medication, wait until the rash is about grade 0 or 1, and then recommend a full dose, or if rash is still a concern, go for a reduced dose.”
By changing and understanding the evolution of new medications that are coming into the clinic, and with symptom management algorithms, we can assure that patients are getting the benefits, said Mainwaring. “Men who had a reduction in dose actually derived the same benefits.”
Results of the SPARTAN trial, reported early this year, showed that apalutamide plus ADT reduced the risk for distant metastasis or death by 72 percent (HR, 0.28, 95 percent confidence interval [CI], 0.23–0.35; p<0.0001) vs placebo. Median metastasis-free survival (MFS) was 40.5 months for apalutamide vs 16.2 months for placebo, for a difference of 24.3 months. [N Engl J Med 2018;378:1408-1418]
Based on SPARTAN findings, apalutamide was subsequently approved for nmCRPC in the US as a second-generation ADT. However, calls for apalutamide to be a new standard of care in the setting of nmCRPC were tempered by concerns about higher AEs vs placebo.
However, in an analysis of apalutamide’s effects on health-related quality of life (HRQoL), HRQoL was maintained following initiation of apalutamide whereas it deteriorated from baseline in those randomized to ADT plus placebo. [Lancet Oncol 2018;19:1404-1416].