TABLE 4.
Clinical Outcomes of BELLE-2 and BELLE-3 According to PKI3CA Mutation Status in Tumor and Plasma
| Variable | Overall Population | ctDNA PIK3CA+ | ctDNA PIK3CA− | Tumor PIK3CA+ | Tumor PIK3CA− | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Buparlisib and Fulvestrant | Placebo and Fulvestrant | Buparlisib and Fulvestrant | Placebo and Fulvestrant | Buparlisib and Fulvestrant | Placebo and Fulvestrant | Buparlisib and Fulvestrant | Placebo and Fulvestrant | Buparlisib and Fulvestrant | Placebo and Fulvestrant | |
| BELLE-2* | ||||||||||
| Patients, n | 576 | 571 | 87 | 113 | 199 | 188 | 21 | 19 | 123 | 120 |
| ORR, % (95% CI) | 11.8 (9.3–14.7) | 7.7% (5.7–10.2) | 18.4 (10.9–28.1) | 3.5 (1.0–8.8) | 11.6 (7.5–16.8) | 10.6% (6.6–16.0) | NR | NR | NR | NR |
| Median PFS, mo (95% CI) | 6.9 (6.8–7.8) | 5.0 (4.0–5.2) | 7.0 (5.0–10.0) | 3.2 (2.0–5.1) | 6.8 (4.7–8.5) | 6.8 (4.7–8.6) | 4.4 (1.6–NE) | 10.7 (3.0–NE) | 5.1 (3.5–8.5) | 4.7 (3.3–8.5) |
| HR (95% CI) | 0.78 (0.67–0.89) | 0.58 (0.41–0.82) | 1.02 (0.79–1.30) | 1.18 (0.49–2.85) | 0.98 (0.72–1.32) | |||||
| p Value | .00021 (1-sided) | .001 (1-sided) | .557 (1-sided) | NR | NR | |||||
| BELLE-3** | ||||||||||
| Patients, n | 289 | 143 | 100 | 35 | 132 | 81 | 75 | 34 | 135 | 69 |
| ORR, % (95% CI) | 3.9 (2.8–4.2) | 1.8 (1.5–2.8) | 4.2 (2.8–6.7) | 1.6 (1.4–2.8) | 3.9 (2.8–4.3) | 2.7 (1.5–3.6) | 4.7 (2.9–6.7) | 1.4 (1.4–2.2) | 2.8 (1.9–3.4) | 1.7 (1.4–2.9) |
| Median PFS, mo (95% CI) | 0.67 (0.53–0.84) | 0.46 (0.29–0.73) | 0.73 (0.53–1.00) | 0.39 (0.23–0.65) | 0.81 (0.59–1.12) | |||||
| HR (95% CI) | .0030 | .0031 | .026 | < .0001 | .099 | |||||
BELLE-2: Women who were estrogen receptor–positive or progesterone receptor–positive, human epidermal growth factor receptor 2–negative, aromatase inhibitor refractory. ctDNA PKI3CA determined by BEAMing polymerase chain reaction; tumor PIK3CA determined by Sanger sequencing.
BELLE-3: Women who were estrogen receptor-positive or progesterone receptor–positive, human epidermal growth factor receptor 2–negative, aromatase inhibitor refractory, and refractory to mTOR inhibition. ctDNA PIK3CA determined by Inostics BEAMing polymerase chain reaction, covering exons 9 and 20; tumor PIK3CA determined by Cobas PIK3CA assay covering exons 7, 9, and 20.
Abbreviations: ORR, overall response rate; NR, not reported; NE, not evaluable; PFS, progression-free survival; HR, hazard ratio.