Table 6.
Available clinical trials evaluating the safety and the efficacy of PI3K inhibitors in combination with anti HER2 agent.
| Drug | Trial | Phase | Regimens | Population | Activity | Toxicities |
|---|---|---|---|---|---|---|
| Alpelisib | NCT02038010 [96] | I | Alpelisib + T-DM1 | HER2+ MBC Progressing on prior trastuzumab and taxane-based therapy | Median PFS (months): No prior T-DM1 (n = 11): 6 Prior T-DM1 (n = 6): 4.3 |
Hyperglycemia (53%), fatigue (53%), nausea (35%), and rash (47%) |
| NCT02167854 [97] | I | LJM716 + alpelisib + Trastuzumab | HER2+ MBC | SD in 5/6 evaluable patients | Significant toxicities (and worst grades): diarrhea, hyperglycemia hypokalemia, mucositis, transaminitis | |
| NCT04208178 | III | Alpelisib + Trastuzumab + Pertuzumab | Maintenance therapy in patients with HER2+ ABC with a PIK3CA mutation | unknown | unknown | |
| Taselisib | NCT02390427 | Ib | Arm A: Taselisib + Trastuzumab + T-DM1 Arm B: Taselisib + T-DM1 + Pertuzumab Arm C: Taselisib + Pertuzumab + Trastuzumab Arm D: Taselisib + Pertuzumab + Trastuzumab + Paclitaxel |
HER2+ ABC | unknown | unknown |
| Copanlisib | NCT02705859 [98] | Ib/2 | Copanlisib + Trastuzumab | HER2+ MBC | SD in 9/12 patients. Six patients continued treatment ≥ 16 weeks |
G3 hypertension (33%), G3 infections (36%), hepatic toxicities |
| MEN1611 | NCT03767335 [99] | Ib | MEN1611 + Trastuzumab +/− Fulvestrant | PIK3CA mutated HER2+ ABC progressed to anti-HER2 based therapy | unknown | unknown |