medwireNews: Chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) derive a significant radiographic progression-free survival (PFS) benefit from the addition of apalutamide to abiraterone acetate, suggest phase 3 trial data.
The final analysis of the ACIS study, conducted at a median follow-up of 54.8 months, was presented by Dana Rathkopf (Memorial Sloan Kettering Cancer Center, New York, USA) at the 2021 Genitourinary Cancers Symposium.
In the trial, 982 men with ongoing androgen deprivation therapy, but no other prior treatment for mCRPC, were randomly assigned to receive abiraterone acetate 1000 mg/day plus prednisone 5 mg twice daily either with or without apalutamide 240 mg/day.
The primary endpoint of investigator-assessed radiographic PFS was significantly improved with the addition of apalutamide to abiraterone, at a median of 24.0 months versus 16.6 months with abiraterone alone. This equated to a 30% reduction in the risk for radiographic progression or death with apalutamide plus abiraterone.
Men receiving the combination were also significantly more likely to achieve a confirmed prostate-specific antigen (PSA) decline of at least 50% than those given just abiraterone, at rates of 79.5% and 72.9%, respectively. But this did not translate into a significant improvement in the median time to PSA progression, which was comparable at a respective 13.8 and 12.0 months, reported Rathkopf.
And although the median overall survival (OS) duration was numerically longer in the combination than the abiraterone group, at 36.2 versus 33.7 months, the between-group difference did not reach statistical significance in the current analysis.
Other secondary endpoints, such as time to initiation of cytotoxic therapy and pain progression, were also similar between the treatment arms, as were exploratory endpoints, such as time to clinical progression and second PFS.
“The safety profile of the combination was consistent with the previously reported safety of the individual drugs and no new safety signals were observed,” said the presenter.
The incidence of grade 3–4 treatment-emergent adverse events (TEAEs, 63.3 vs 56.2%), serious AEs (37.3 vs 31.1%), and TEAEs leading to discontinuation (9.4 vs 6.3%) were “slightly higher” in the combination than the abiraterone group, but the rate of TEAEs associated with death was lower (3.5 vs 7.6%), she added.
Rathkopf highlighted that among the TEAEs of special interest, hypertension, rash, and fractures – “which are known side effects of apalutamide” – occurred more frequently in the combination versus the abiraterone arm.
Nonetheless, health-related quality of life, as evaluated by the FACT-P total score, remained comparable between the study groups through the course of the study.
Discussant Joshi Alumkal (University of Michigan Rogel Cancer Center, Ann Arbor, USA) said that the large sample size and use of a standard of care as the control are “clear strengths” of the trial. But he pointed out the increased toxicity and “potential high costs” with the combination as limitations.
Alumkal also stressed the lack of a significant OS benefit at present with the addition of apalutamide to abiraterone, which “may be due to immature follow-up, but the similar second PFS between groups suggests that subsequent therapy may have worked less well in those treated on-study in the combination arm.”
In light of these limitations and clinical insights from other studies of combined or sequential androgen receptor signaling inhibitor treatments, “I do not believe results from ACIS change practice at this time,” he concluded.
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