Phase II randomized study of abiraterone acetate plus prednisone (AAP) added to ADT versus apalutamide alone (APA) versus AAP+APA in patients with advanced prostate cancer with noncastrate testosterone levels: (LACOG 0415)

5505 Background: ADT combined with AAP, APA, enzalutamide or docetaxel are among the standard treatment options to patients (pts) with hormone sensitive advanced/metastatic prostate cancer (PC). However, treatment-related adverse events (TRAEs) due to ADT impact negatively on the quality of life of these patients. Effective options with fewer TRAEs are required. Methods: LACOG 0415 is a phase II, randomized trial (1:1:1) evaluating the use of AA 1000mg po + prednisone 5mg po BID + ADT versus APA 240mg po alone versus AA 1000mg po + prednisone 5mg po BID + APA 240mg po in patients with advanced PC with non-castrate testosterone levels and indication of ADT (N+ or M+ or biochemical relapse combined with PSA ≥ 20 ng/ml or with PSA≥4 ng/ml and PSA doubling-time < 10 months). Stratification factors: metastatic disease (+/-). Primary endpoint was the percentage of pts who achieved PSA ≤ 0.2 ng/mL at Week 25, we estimated a PSA response rate of 65% in each of the three arms with a null hypothesis of 45%, power of 80% and alfa 5%, using Fleming one-stage method. Secondary endpoints were percentage of pts with ≥ 80% and ≥ 50% decline in PSA at week 25, radiographic progression-free survival (rPFS) and safety. Results: 128 patients were randomized between Oct 2017 and Apr 2019, and 122 pts were evaluable for PSA response. Median age was 69y (range, 53-88); most pts had ECOG PS0-1(99%). 17% of pts had biochemical relapse only, 9% N+ and 74% M+ disease. At week 25 the PSA was ≤ 0.2 ng/mL in 76% of pts in AAP+ADT arm, 59% in APA, and 80% in APA+AAP. All pts had a decline of ≥ 50% in PSA at week 25. 97% had a decline of ≥ 80% in PSA at week 25: 100% of pts in AAP+ADT arm, 95% in APA and 98% in APA+AAP. A total of 3 pts had clinical progressive disease, one in each arm. Two of them also had radiological progression at week 25, 1 pt in AAP+ADT arm and 1 pt in APA. TRAEs rates of any grade were 71% in AAP+ADT arm, 64% in APA, and 65% in APA+AAP. TRAEs rates of Grade≥3 were 12% in AAP+ADT arm, 9% in APA and 16% in APA+AAP. 9 pts (7%) discontinued the treatment before the week 25, 5(4%) of them due to toxicity: 1 pt from AAP+ADT, 2 pts from APA, and 6 pts from APA+AAP. Conclusions: The AAP+ADT and APA+AAP groups showed high effectiveness in terms of PSA response. Radiologic disease control and the decline of ≥ 80% in PSA at week 25 were similar among all treatment arms. APA alone had less toxicity. APA+AAP and APA alone are promising regimens in this setting. No new safety signal was detected in the study. Clinical trial information: NCT02867020 .