medwireNews: Administration of abiraterone acetate alongside first-line androgen deprivation therapy (ADT) could be the new standard of care for men with locally advanced or metastatic prostate cancer, say the authors of two independent phase III trials.
As reported at the 2017 annual meeting of the American Society of Clinical Oncology, overall survival (OS) was significantly longer in the LATITUDE trial for the 597 men with newly diagnosed, metastatic, castration-sensitive disease who were randomly assigned to receive abiraterone acetate 1000 mg/day plus prednisone 5 mg/day together with ADT than for their 602 counterparts given ADT plus placebos, with the median not reached and 34.7 months, respectively.
Presenting author Karim Fizazi (Gustave Roussy, Villejuif, France) told the audience in Chicago, Illinois, USA, that this equated to a significant 38% reduced risk for death for patients given abiraterone.
Abiraterone-treated patients remained radiographic progression-free for a median of 33.0 months, compared with 14.8 months for those given ADT plus placebos; the risk for radiographic progression or death was 53% lower in the abiraterone than the control group.
Other endpoints were also significantly improved with the addition of abiraterone to ADT, including a significant 30% and 70% reduction in time to pain progression and prostate-specific antigen (PSA) progression, respectively.
The LATITUDE investigators point out in the article simultaneously published in The New England Journal of Medicine that “the early use of abiraterone plus prednisone resulted in increased survival, even though more patients in the placebo group received life-prolonging treatments after progression,” with respective rates of 40% and 52% in the abiraterone and control arms.
They also note that “[t]hese findings led to the unanimous recommendation by the independent data and safety monitoring committee that the trial be unblinded and crossover be allowed for patients in the placebo group to receive abiraterone,” making this first interim analysis the final analysis of the study.
Fizazi concluded his presentation by commenting that adding abiraterone plus prednisone to ADT “can potentially be considered a new standard of care” for this patient population.
The STAMPEDE trial, the results of which were presented by Nicholas James (Queen Elizabeth Hospital, Birmingham, UK) at the meeting and also concurrently published in The New England Journal of Medicine, arrived at a very similar conclusion.
Among 1917 men with locally advanced or metastatic prostate cancer who initiated ADT between 2011 and 2014, the risk for death was a significant 37% lower for the 960 patients who were randomly allocated to receive abiraterone and prednisone (at the same dose as in the LATITUDE trial) alongside ADT than for the 957 given ADT alone.
The risk for treatment failure – defined as radiologic, clinical, or PSA progression or prostate cancer-specific-death – was also reduced with the addition of abiraterone, by a significant 71%.
James reported that the 3-year OS and treatment failure-free survival rates in the combination and ADT alone groups were 83% versus 76% and 75% versus 45%, respectively.
He added that the results were consistent across subgroups and that there was “no good evidence for heterogeneity by stratification factors,” such as metastatic status and WHO performance status, indicating that the results apply to the whole trial population.
As such, abiraterone plus prednisone “should be part of the standard of care for men starting long-term androgen deprivation therapy,” the presenter concluded.
Tanya Dorff, from the Keck School of Medicine of University of Southern California in the USA, who discussed the STAMPEDE trial at the meeting pointed out, however, that the OS gain offered by the addition of abiraterone was really only significant among the 52% of men with metastatic disease and not for the nonmetastatic population.
Nonetheless, she highlighted the “striking benefit” afforded by upfront abiraterone in patients with metastatic disease.
The safety profile of abiraterone in the LATITUDE and STAMPEDE trials was consistent with that seen in previous studies. Adverse events of grade 3 or worse occurred more often in the combination compared with the ADT alone arm in both trials, at a rate of 63% versus 48% in LATITUDE and 47% versus 33% in STAMPEDE.
The most common grade 3 or worse toxicities associated with abiraterone addition were also similar in the studies, namely cardiovascular disorders (including hypertension) and elevated liver enzymes. The LATITUDE investigators also observed an increased incidence of grade 3 or worse hypokalemia among abiraterone-treated patients relative to those in the control group.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group