Final results of LATITUDE confirm the benefit of abiraterone acetate plus prednisone along with ADT in high-risk metastatic castration-sensitive prostate cancer.
The combination of abiraterone acetate plus prednisone along with androgen deprivation therapy (ADT) resulted in significantly longer survival than placebo and ADT in men with newly diagnosed high-risk metastatic castration-sensitive prostate cancer, according to the long-term results of the LATITUDE study.
Previous research showed that abiraterone acetate along with prednisone can improve outcomes in both chemotherapy-naive and chemotherapy-treated castration-resistant patients, and its combination with luteinizing hormone-releasing hormone (LHRH) agonists led to a lowering of prostate tissue antigens. “This finding suggests that abiraterone acetate plus prednisone might also inhibit extragonadal androgen biosynthesis and thereby help delay the emergence of resistance in patients with metastatic castration-sensitive prostate cancer,” wrote study authors led by Karim Fizazi, MD, of the Institut Gustave Roussy in Villejuif, France.
The phase III LATITUDE trial included 1,199 patients across 235 sites and 34 countries; an interim analysis previously found improved overall survival and radiographic progression–free survival with abiraterone acetate plus prednisone and ADT compared with placebo and ADT. After that analysis, the trial was unmasked, and patients in the placebo group were allowed to cross over. The US Food and Drug Administration approved the treatment in early 2018. This final analysis was done after a median follow-up of 51.8 months, during which 618 patients died. The results were published in Lancet Oncology.
Overall survival was significantly longer in the abiraterone acetate group, at a median of 53.3 months, compared with 36.5 months in the placebo group, for a hazard ratio of 0.66 (95% CI, 0.56–0.78; P < .0001). Overall survival was better with abiraterone acetate plus prednisone across patient subgroups, with the exception of those with an ECOG performance status of 2 and those with a Gleason score of less than 8, for which there was no significant difference.
Secondary endpoints were also consistent with the interim analysis, with better results in terms of time to pain progression, symptomatic skeletal-related events, chemotherapy initiation, subsequent therapy for prostate cancer, and prostate-specific antigen progression, as well as for an exploratory analysis of secondary progression-free survival.
The total incidence of adverse events was similar across the two groups, with more than 90% of patients experiencing any event. With abiraterone acetate plus prednisone, grade 3/4 adverse events were reported in 68% of patients, compared with 50% of the placebo patients. Serious adverse events occurred in 32% of abiraterone acetate plus prednisone patients, 25% of placebo patients, and 6% of patients who crossed over from the placebo group after unmasking.
“The final updated data underscore significant survival benefits of adding abiraterone acetate plus prednisone to ADT in newly diagnosed patients with high-risk metastatic castration-sensitive prostate cancer, by further prolonging the overall survival, along with a delay in initiation of chemotherapy and need for subsequent therapy,” the authors concluded. “These findings thus reinforce the use of abiraterone acetate plus prednisone as a standard of care for patients with high-risk metastatic castration-sensitive prostate cancer.”
In an accompanying editorial, Fred Saad, MD, of the University of Montreal, wrote that the results of the LATITUDE trial “clearly show the value of early aggressive therapy in managing aggressive and rapidly lethal prostate cancer.” The outstanding question, he noted, is whether metastatic castration-sensitive prostate cancer patients would fare better with chemotherapy or the abiraterone plus ADT combination. “Unfortunately, the outlook is poor for these high-risk patients with either approach, so ongoing research is assessing the upfront combination of docetaxel plus a new-generation hormonal therapy,” Saad wrote.