Table 2.
PI3K inhibitor with publicly available clinical data arising from at least a phase II study in solid tumours are reported.
| Drug | Study ID | Phase | Indications | Experimental treatment | Control | ORR | mPFS (months) | Discontinuation rate (due to AE) |
|---|---|---|---|---|---|---|---|---|
| Pictilisib (GDC-0941) | FERG1 [23] | II | HR + HER2-BC (Part 1: previous aromatase inhibitor; regardless of PIK3CA mutation) | Pictilisib + Fulvestrant | Placebo + Fulvestrant | 7.9% vs 6.3% | 6.6 vs 5.1; HR 0.74 (0.51–1.06, p = 0.096) | 18% vs 3% |
| HR + HER2− BC (Part 2: previous aromatase inhibitor; PTs with PIK3CA mutation) | Pictilisib + Fulvestrant | Placebo + Fulvestrant | 7.3% vs 5% | 5.4 vs 10; HR 1.07 (0.53–2.18, p = 0.84) | 24% vs 5% | |||
| PEGGY [24] | II | HR + HER2− BC (chemo-naive with exception of previous Capecitabine; regardless of PIK3CA mutation) | Pictilisib + Paclitaxel | Placebo + Paclitaxel | 22% vs 19.6% | 8.2 vs 7.8; HR 0.95 (0.62–1.46, p = 0.83) | 25% vs 15.2% | |
| Pilaralisib (XL147) | NCT01013324 [25] | II | Advanced endometrial cancer (progressing to 1/2 previous CT lines; regardless of PIK3CA mutation) | Pilaralisib | NA | 6% | NA | 20.9% |
| Sonolisib (PX-866) | NCT01204099 [26, 27] | II | Advanced NSCLC (progressing to 1/2 previous CT lines; regardless of PIK3CA mutation) | PX-866 + Docetaxel | Placebo + Docetaxel | 6% vs 0% | 2 vs 2.9; HR NA | 0% vs 5% |
| Advanced HNSCC (progressing to 1/2 previous CT lines; regardless of PIK3CA mutation) | PX-866 + Docetaxel | Placebo + Docetaxel | 14% vs 5% | 3 vs 2.7; HR NA | NA | |||
| Buparlisib (BKM120) | BELLE-2 [29] | III | HR + HER2− BC (previous aromatase inhibitor) | Buparlisib + Fulvestrant | Placebo + Fulvestrant | 11.8% vs 7.7% | 6.9 vs 5.0; HR 0.78 (0.67–0.89, p < 0.001) | 39% vs 5% |
| BELLE-3 [28] | III | HR + HER2− BC (previous aromatase inhibitor and mTORi) | Buparlisib + Fulvestrant | Placebo + Fulvestrant | 8% vs 2% | 3.9 vs 1.8; HR 0.67 (0.53–0.84, p < 0.001) | 21% vs 5% | |
| BELLE-4 [30] | II/III | HER2-BC (chemo-naive) | Buparlisib + Paclitaxel | Placebo + Paclitaxel | 22.6% vs 27% | 8.0 vs 9.2; HR 1.18 (0.81–1.68) | 20.8% vs 7.2% | |
| BERIL-1 [31] | II | HNSCC | Buparlisib + Paclitaxel | Placebo + paclitaxel | 39% vs 14% | 4.6 vs 3.5; HR 0.65 (0.45–0.95, p = 0.011) | 10% vs 14% | |
| Copanlisib (BAY 80-6946) | NCI-MATCH [32] | II | Solid tumours (PIK3CA mutant and PTEN loss) | Copanlisib | NA | 16% | NA | 10% |
| Alpelisib (NVP-BYL719) | Solar-1 [6, 33] | III | PIK3CA mutant HR + HER2− BC (previous aromatase inhibitor, CDK4/6 inhibitor permitted) | Alpelisib + Fulvestrant | Placebo + Fulvestrant | 26.6% vs 12.8% | 11 vs 5.7; HR 0.65 (0.50–0.85, p < 0.001) | 25% vs 4.2% |
| BYLieve [37] | II | PIK3CA mutant HR + HER2− BC (previous CDK4/6 inhibitors + aromatase inhibitor or previous CDK4/6 inhibitor + Fulvestrant or previous chemotherapy) | Alpelisib + Fulvestrant | NA | 17% | 7.3 | 20% | |
| Eganelisib (IPI-549) | Mario-275a (NCT03980041) | II | Urothelial cancer (immunotherapy naive, platinum refractory) | Eganelisib + Nivolumab | Placebo + Nivolumab | 30% vs 25% | NA | NA |
| Mario-3 [43] | II | TNBC | Eganelisib + Atezolizumab + Nab-Paclitaxel | NA | NA | NA | NA | |
| Taselisib (GDC-0032) | Sandpiper [46] | III | PIK3CA mutant HR + HER2− BC (previous aromatase inhibitor) | Taselisib + Fulvestrant | Placebo + Fulvestrant | 28% vs 11.9% | 7.4 vs 5.4; HR 0.7 (p = 0.0037) | 17% vs 2% |
ORR overall response rate, mPFS median progression-free survival, AE adverse event, BC breast cancer, HR hormone receptor, HER2 Human Epidermal Growth Factor Receptor 2, mTORi: mammalian target of rapamycin inhibitor, PIK3CA phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha, NSCLC non-small cell lung cancer, CT chemotherapy, HNSCC head and neck squamous cell carcinoma, CDK cyclin-dependent kinase, TNBC triple-negative breast cancer, NA not available.
aFor Mario-275 trial, the only available data arise from press releases, we chose to report them here since, if confirmed on peer reviewed sources, they might be relevant in the future.