Phase III ACIS study of Erleada and Zytiga meets primary endpoint in prostate cancer.- Janssen Pharma

The Janssen Pharmaceutical Companies of Johnson & Johnson announced results from the randomized, double-blind, placebo-controlled Phase III ACIS study of Erleada (apalutamide) and Zytiga (abiraterone acetate) plus prednisone, which met the primary endpoint of radiographic progression-free survival (rPFS) with a 31 percent reduction in the risk of radiographic progression or death in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) receiving androgen deprivation therapy (ADT). Patients in the trial received either a combination of Erleada and Zytiga plus prednisone (combination arm) or placebo and Zytiga plus prednisone (control arm). The primary efficacy analysis showed median rPFS was extended by six months in patients treated in the combination arm compared with patients in the control arm (22.6 vs. 16.6 months; hazard ratio [HR] 0.69 [95% CI, 0.58-0.83]; p<0.0001). the hr for radiographic progression or death as assessed by blinded independent central review (bicr) was 0.864 [95% ci, 0.718–1.040]. according to an updated analysis performed at a median follow-up of 54.8 months, a 30 percent reduction in the risk of radiographic progression or death was shown in the combination arm compared with the control arm (median time to rpfs 24 vs. 16.6 months: hr 0.70 [95% ci, 0.60-0.83]). no statistically significant difference was demonstrated for secondary endpoints including overall survival (os), time to initiation of cytotoxic chemotherapy, chronic opioid use, and pain progression between treatment arms. the overall acis study population was heterogenous in markers of androgen receptor (ar) resistance and sensitivity. data from a prespecified analysis showed that patients aged 75 years or older and those with visceral metastasis, luminal type in pam50 test and tumors with average or high ar activity (molecular signatures of hormone sensitivity) may derive clinical benefit from erleada and zytiga plus prednisone combination treatment, as suggested by rpfs and os results in these subgroups. the safety profile was consistent with prior studies of erleada, with no new safety signals observed. grade 3 4 treatment emergent adverse events (teaes) were reported in 63.3 percent of patients in the combination arm versus 56.2 percent in the control arm.1 grade 3 4 teaes that occurred more frequently in the combination versus control arm included fatigue (4.7 percent vs. 3.9 percent), hypertension (20.6 versus 12.5 percent), fall (3.3 percent vs. 0.6 percent), skin rash (4.5 percent vs. 0.4 percent), cardiac disorders (9 percent vs. 5.7 percent), fractures and osteoporosis (4.1 percent vs. 1.4 percent), and seizures (0.2 percent vs. 0). quality of life was comparable between treatment arms per functional assessment of cancer therapy–prostate (fact-p total). acis is a phase iii randomized, double-blind, placebo-controlled, multicenter clinical study evaluating the efficacy and safety of erleada and zytiga plus prednisone compared to placebo and zytiga plus prednisone in 982 patients with chemotherapy-naïve mcrpc disease who received adt. patients were randomized to receive either erleada and zytiga plus prednisone, or placebo and zytiga plus prednisone. the primary endpoint of the study was rpfs. secondary endpoints of the study included os, time to chronic opioid use, time to initiation of cytotoxic chemotherapy, and time to pain progression.results will be featured in an oral presentation at the american society of clinical oncology's genitourinary (asco gu) cancers symposium, taking place virtually february 11-13, 2021 (abstract #9; oral abstract session: prostate cancer, february 11, 12:45 pm-2:00 pm est).>