Article Figures & Data
Figures
- Figure 1.
Trial profile. *One patient was randomized to the placebo group but received 5 consecutive days of ipatasertib and therefore was assigned to ipatasertib 200 mg for safety analysis.
- Figure 2.
Overall population: rPFS (A), OS (B), and time to PSA progression (C) Kaplan–Meier plots. An rPFS event is defined by RECIST progressive disease of soft tissue, bone scan progressive disease, or death within 30 days of last dose. PSA progression is defined as a ≥25% relative increase and an absolute increase of ≥2 ng/mL above the baseline or nadir that is confirmed by a second consecutive value ≥3 weeks later. All HRs are stratified with 90% CIs. Abi, abiraterone; Ipat, ipatasertib; mo, months.
- Figure 3.
PTEN loss and nonloss subpopulations (ICR IHC assay) for rPFS. Abi, abiraterone; Ipat, ipatasertib; mo, months.
Tables
- Table 1.
Baseline demographics and clinical characteristics
Ipatasertib 400 mg + abiraterone Ipatasertib 200 mg + abiraterone Placebo + abiraterone Characteristics (n = 84) (n = 86) (n = 83) Stratification factors (%) Prior enzalutamide 7 (8) 9 (10) 7 (8) Progression factor at trial entry, n (%) PSA + radiographic 42 (50) 42 (49) 47 (57) PSA only 36 (43) 32 (37) 30 (36) Radiographic only 6 (7) 12 (14) 6 (7) Number of prior chemotherapy regimens for metastatic disease 1 69 (82) 69 (80) 62 (75) >1 15 (18) 17 (20) 21 (25) Other factors Age, mean (SD), y 66.9 (8.5) 68.8 (7.2) 67.6 (7.8) Stage IV at diagnosis, n (%) 52 (68) 40 (51) 45 (56) ECOG PS at enrollment, n (%) 0 43 (51) 38 (44) 32 (39) 1 41 (49) 47 (55) 51 (61) Gleason score, n (%) ≤7 31 (37) 30 (35) 34 (41) ≥8 48 (57) 52 (61) 46 (55) Sites of metastatic disease, n (%) Liver 9 (11) 9 (10) 8 (10) Lung 11 (13) 16 (19) 8 (10) Bone 77 (93) 80 (93) 78 (94) Lymph node 42 (51) 43 (50) 40 (48) PSA, mean (SD), μg/L 379 (1012) 261 (623) 230 (329) Alkaline phosphatase, IU/mL 198 (220) 217 (301) 251 (326) Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; y, years.
- Table 2.
PTEN loss and nonloss subpopulations by the four PTEN diagnostic assays tested for (A) rPFS and (B) OS
A Primary analysis Exploratory analysis ICR IHC Ventana IHC FISH NGS PTEN loss PTEN nonloss PTEN loss PTEN nonloss PTEN loss PTEN nonloss PTEN loss PTEN nonloss 400 mg ipatasertib + abiraterone Patients, n 25 32 26 22 28 38 15 21 Patients with events, n (%) 15 (60.0) 20 (62.5) 16 (61.5) 14 (63.6) 15 (53.6) 25 (65.8) 7 (46.7) 14 (66.7) rPFS, median months Ipatasertib 11.5 7.5 11.0 7.5 13.7 6.5 13.8 7.4 Placebo 4.6 5.6 4.6 5.7 6.5 5.6 6.2 4.5 rPFS HR 0.39 0.84 0.50 0.74 0.67 0.77 0.24 0.52 90% CI 0.22–0.70 0.51–1.37 0.29–0.87 0.41–1.32 0.36–1.24 0.50–1.20 0.10–0.60 0.25–1.02 200 mg ipatasertib + abiraterone Patients, n 25 27 31 16 22 47 13 16 Patients with events, n (%) 16 (64.0) 20 (74.1) 21 (67.7) 12 (75.0) 15 (68.2) 31 (66.0) 9 (69.2) 10 (62.5) rPFS, median months Ipatasertib 11.1 4.6 8.5 6.4 10.5 6.7 8.3 8.6 Placebo 4.6 5.6 4.6 5.7 6.5 5.6 6.2 4.5 rPFS HR 0.46 1.13 0.66 1.04 0.87 0.74 0.55 0.53 90% CI 0.25–0.83 0.69–1.85 0.39–1.11 0.57–1.92 0.47–1.61 0.49–1.13 0.24–1.27 0.25–1.13 Placebo + abiraterone Patients, n 21 35 25 26 21 40 11 13 Patients with events, n (%) 18 (85.7) 26 (74.3) 20 (80.0) 19 (73.1) 14 (66.7) 31 (77.5) 10 (90.9) 11 (84.6) B Primary analysis Exploratory analysis ICR IHC Ventana IHC FISH NGS PTEN loss PTEN nonloss PTEN loss PTEN nonloss PTEN loss PTEN nonloss PTEN loss PTEN nonloss Ipatasertib 400 mg + abiraterone Patients, n 25 32 26 22 28 38 15 21 Patients with events, n (%) 9 (36.0) 9 (28.1) 10 (38.5) 5 (22.7) 9 (32.1) 15 (39.5) 5 (33.3) 7 (33.3) OS, median months Ipatasertib 19.15 17.22 19.15 15.57 19.15 17.22 NE 19.15 Placebo 14.75 13.77 12.81 13.77 18.43 11.83 14.75 13.77 OS HR 0.62 0.56 0.65 0.54 0.89 0.62 0.44 0.54 90% CI (0.29–1.33) (0.28–1.13) (0.33–1.28) (0.22–1.29) (0.40–1.99) (0.35–1.08) (0.15–1.29) (0.21–1.40) Ipatasertib 200 mg + abiraterone Patients, n 25 27 31 16 22 47 13 16 Patients with events, n (%) 8 (32.0) 13 (48.1) 13 (41.9) 7 (43.8) 10 (45.5) 20 (42.6) 6 (46.2) 7 (43.8) OS, median months Ipatasertib NE 10.68 NE 13.44 13.44 16.36 NE 13.44 Placebo 14.75 13.77 12.81 13.77 18.43 11.83 14.75 13.77 OS HR 0.64 1.19 0.83 0.98 1.7 0.72 1.13 0.79 90% CI (0.30–1.37) (0.64–2.22) (0.44–1.56) (0.45–2.14) (0.77–3.73) (0.43–1.21) (0.43–2.93) (0.31–1.97) Placebo + abiraterone Patients, n 21 35 25 26 21 40 11 13 Patients with events, n (%) 12 (57.1) 16 (45.7) 14 (56.0) 13 (50.0) 8 (38.1) 22 (55.0) 6 (54.5) 6 (46.2) Abbreviation: NE, not estimable.
- Table 3.
AEs (≥25% in any cohort) by preferred term
Ipatasertib 400 mg + abiraterone Ipatasertib 200 mg + abiraterone Placebo + abiraterone AE, n (%) (n = 84) (n = 87) (n = 82) Total patients with AEs 83 (98.8) 82 (94.3) 76 (92.7) Total patients with grade ≥3 AEs 54 (64.3) 44 (50.6) 29 (35.4) Total patients with SAEs 36 (42.9) 35 (40.2) 15 (18.3) Deaths 30 (35.7) 36 (41.4) 38 (46.3) Due to AEs 4 (4.8) 6 (6.9) 4 (4.9) Diarrhea, any grade 64 (76.2) 39 (44.8) 21 (25.6) Grade 3 10 (11.9) 2 (2.3) 1 (1.2) Grade 4 0 0 0 SAE 2 (2.4) 1 (1.1) 0 Asthenia, any grade 23 (27.4) 17 (19.5) 13 (15.9) Grade 3 5 (6.0) 1 (1.1) 1 (1.2) Grade 4 0 0 0 SAE 1 (1.2) 0 0 Fatigue, any grade 21 (25.0) 22 (25.3) 24 (29.3) Grade 3 3 (3.6) 3 (3.4) 2 (2.4) Grade 4 0 0 0 SAE 0 0 1 (1.2) Decreased appetite, any grade 21 (25.0) 19 (21.8) 12 (14.6) Grade 3 1 (1.2) 0 0 Grade 4 0 0 0 SAE 0 0 0 Back pain, any grade 15 (17.9) 18 (20.7) 21 (25.6) Grade 3 1 (1.2) 3 (3.4) 1 (1.2) Grade 4 0 0 0 SAE 1 (1.2) 1 (1.1) 1 (1.2) Nausea, any grade 44 (52.4) 30 (34.5) 20 (24.4) Grade 3 2 (2.4) 0 0 Grade 4 0 0 0 SAE 0 0 1 (1.2) Vomiting, any grade 26 (31.0) 24 (27.6) 12 (14.6) Grade 3 0 1 (1.1) 0 Grade 4 0 0 0 SAE 0 0 1 (1.2) Abbreviation: SAE, serious AE.
Supplementary Data
- Supplemental data - Includes supplementary methods, figures, and tables.
Volume 25, Issue 3
