Table 3.
Summary of clinical activity of phosphatidylinositol 3-kinase (PI3K) inhibitors in phase I clinical trials
| Agent/dose | N | Selected | Tumor type with PR (RECIST) | Molecular profile status | References |
|---|---|---|---|---|---|
| Pan-isoform PI3K inhibitors | |||||
| SAR245408 (XL147) | 75 | No | NSCLC | No alteration | [6] |
| BKM120 | 66 | No (expansion only) | TN breast | KRAS mutation | [7] |
| ER+ HER2- breast | PIK3CA mutation | ||||
| Parotid cancer | PIK3CA mutation | ||||
| GDC-0941 | |||||
| Once a day | 42 | No | Melanoma | BRAF V600E mutation | [8] |
| Once a day or twice a day | 97 | No | ER+, HER2- breast | Unknown | [9] |
| Endocervical adenocarcinoma | PIK3CA mutation | ||||
| BAY 80-9646 | |||||
| Dose escalation | 17 | No | None | - | [10] |
| Expansion: solid | 30 | No | ER+ HER2- Breast | No alteration | [11] |
| ER+ HER2+ Breast | HER2 amplification | ||||
| Expansion: NHL | 5 | No | Follicular lymphoma (5 patients) | No alteration (0 of 5 patients) | [11] |
| CH5132799 | 31 | No | None | -a | [12] |
| PX-866 | 84b | No | None | - | [13] |
| Pan-isoform PI3K-mTOR inhibitors | |||||
| SAR245409 (XL765) | |||||
| Solid tumors | 83 | No | None | - | [14] |
| Lymphoma | 16 | No | Mantle cell lymphoma | Unknown | [15] |
| Transformed lymphoma | Unknown | ||||
| Diffuse large B-cell lymphoma | Unknown | ||||
| BEZ235 | |||||
| Once a day | 59c | No (expansion only) | ER+ HER2- breast | Unknown | [16] |
| NSCLC | PTEN mutation (Cowden) | ||||
| Twice a day | 16 | No | None | - | [17] |
| GSK2126458 | 129 | No (expansion only) | Renal | No alteration | [18] |
| Renal | PTEN loss | ||||
| Bladder | PIK3CA mutation | ||||
| Bladder | Unknown | ||||
| GDC-0980 | 42 | No | Adrenal cortical | Unknown | [19] |
| 32 | No | None | - | [20] | |
| SF-1126 | 39 | No | None | - | [21] |
| PF-04691502 | 33 | No | None | - | [22] |
| PF-05212384 | 53 | No (expansion only) | Ovarian cancer | No alteration | [23] |
| NSCLC | EGFR mutation | ||||
| BGT-226 | 57 | No | None | - | [24] |
| PI3Kα-specific inhibitors | |||||
| BYL719 | 35 | Yes | ER+ breast | PIK3CA mutation | [25] |
| Cervix | PIK3CA mutation | ||||
| Colon | PIK3CA and KRAS mutations | ||||
| PI3Kδ-specific inhibitors | |||||
| GS-1101 | |||||
| CLL | 54 | No | 26% RR according to IWCLL | Unknown | [26] |
| Non-Hodgkin's lymphoma | 49 | No | Indolent NHL (15 PR out of 24); mantle cell lymphoma (10 PR out of 16) | Unknown | [27] |
aPatient with ovarian cancer, with PIK3CA mutation still receiving treatment, with -17.2% reduction of target lesions and 75% decrease in CA-125.
bA total of 56 patients evaluable for response.
cA total of 51 patients evaluable for response.
BRAF = v-raf murine sarcoma viral oncogene homolog B1; CA = cancer antigen; CLL = chronic lymphocytic leukemia; EGFR = epidermal growth factor receptor; ER = estrogen receptor; HER2 = human epidermal growth factor receptor 2; IWCLL = International Workshop on Chronic Lymphocytic Leukemia; KRAS = v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog; mTOR = mammalian target of rapamycin; NHL = non-Hodgkin's lymphoma; NSCLC = non-small cell lung cancer; PIK3CA = phosphatidylinositol 3-kinase p110α isoform gene; PR = partial response; RECIST = Response Evaluation Criteria In Solid Tumors; RR = response rate; TN = triple negative.