Phase Ii Randomized Study Of Abiraterone Acetate Plus Prednisone (Aap) Added To Adt Versus Apalutamide Alone (Apa) Versus Aap Plus 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 .