Table 1. Different trials testing the PIK3CA inhibitors in post-menopausal metastatic luminal breast cancer.
| Trial | Population: mBC HR + HER2 − | Endocrine therapy | Number of
patients |
Results |
|---|---|---|---|---|
| BELLE-2
(phase III) 51 |
PD after AI (one line of
chemotherapy in metastatic disease was allowed; design similar to that of PALOMA-3 trial) |
Buparlisib + FVL
versus FVL |
1147 | - Better mPFS in both PIK3CA mutated or wild-type
• wild-type: mPFS increased from 4.5 to 6.8 months (hazard ratio 0.8; P = 0.0033) • mutated: mPFS increased from 4 to 6.8 months (hazard ratio 0.76; P = 0.0014) - Bad toxicity profile with 23% SAE in buparlisib group |
| BELLE-3
(phase III) 52 |
PD after mammalian target of
rapamycin (mTOR) inhibitor |
Buparlisib + FVL
versus FVL |
432 | - mPFS increased from 1.8 to 3.9 months
(hazard ratio 0.67; P = 0.00030) - Significant toxicity profile with 22% SAE in buparlisib group |
| FERGI (part 2
of phase II) 53 |
PD after AI (part 2 cohort
including PI3KCA mutated tumors only) |
Pictilisib + FVL
versus FVL |
61 | - No statistically significant difference in mPFS
- Significant toxicity profile with 36% of at least grade 3 AE and 5% SAE in pictilisib group |
| SANDPIPER
(phase III) 54 |
PD after AI (PIK3CA-mutated
tumors only) |
Taselisib (selective
PI3K inhibitor) + FVL versus FVL |
516 | - mPFS increased from 5.7 to 7.4 months
(hazard ratio 0.7; P = 0.0037) - Taselisib group: at least grade 3 AEs: 12% diarrhea, 10% hyperglycemia, 3% colitis, 2% stomatitis, and treatment discontinuation in 17% |
| SOLAR-1
(phase III) 37, 38 |
PD after AI with or without a
cyclin-dependent kinase 4/6 (CDK4/6) inhibitor |
Alpelisib (α-specific
PI3K inhibitor) + FVL versus FVL |
572 | - mPFS increased from 5.7 to 11 months
(hazard ratio 0.65; P = 0.00065) in mutated tumors - Alpelisib group: grade 3 AE: 32.7% hyperglycemia, 9.9% rash, and 6.7% diarrhea |
AE, adverse event; AI, aromatase inhibitor; FVL, fulvestrant; HER2 −, human epidermal growth factor receptor 2–negative; HR +, hormone receptor–positive; mBC, metastatic breast cancer; mPFS, median progression-free survival; PD, progression disease; SAE, serious adverse event.