Table 1. Characteristics of the included studies.
| Study | Publish year | Tumor type | Trial phase | Experiment arm targeted reagents type | Control arm or experiment arm combined targeted reagents type | General protocol | Patients numbers in experimental arm | Patients numbers in control arm | Primary end-point | Other end-point | Reported the PI3K mutant data (yes/no) | Jaded Score |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Andre (BOLERO-3) | 2014 | Breast cancer | III | mTORC1 | HER2 | Everolimus+ Vinorelbine+ trastuzumab vs placebo+Vinorelbine+ trastuzumab | 284 | 285 | PFS | NA | yes | 5 |
| Bachelot (GINECO) | 2012 | Breast cancer | II | mTORC1 | NA | Everolimus+ tamoxifen vs tamoxifen | 54 | 57 | CBR | TTP, OS | no | 4 |
| Baselga (BOLERO-2) | 2012 | Breast cancer | III | mTORC1 | NA | Everolimus + exemestane vs placebo+ exemestane | 485 | 239 | PFS | OS | no | 5 |
| Baselga (BELLE-2) | 2017 | Breast cancer | III | Pan-PI3K | NA | Buparlisib+ fulvestrant vs placebo+ fulvestrant | 576 | 571 | PFS | NA | yes | 5 |
| Baselga* | 2017 | Breast cancer | II | mTORC1 | NA | Ridaforolimus+ dalotuzumab+ exemestane vs exemestane | 29 | 33 | PFS | OS | no | 4 |
| Hurvitz (BOLERO-1) | 2015 | Breast cancer | III | mTORC1 | HER2 | Everolimus+ Trastuzumab+ Paclitaxel vs placebo+ Trastuzumab+ Paclitaxel | 480 | 239 | PFS | NA | no | 5 |
| Kim (LOTUS) | 2017 | Breast cancer | II | AKT | NA | Ipatasertib+ paclitaxel vs placebo+ paclitaxel | 62 | 62 | PFS | NA | yes | 5 |
| Krop (FERGI) | 2016 | Breast cancer | II | Pan-PI3K | NA | Pictilisib+ fulvestrant vs placebo+ fulvestrant | 89 | 79 | PFS | NA | yes | 5 |
| Martin (BELLE-4) | 2016 | Breast cancer | III | Pan-PI3K | NA | Buparlisib+ paclitaxel vs placebo+ paclitaxel | 207 | 209 | PFS | NA | yes | 5 |
| Vuylsteke (PEGGY) | 2016 | Breast cancer | II | Pan-PI3K | NA | Pictilisib+ paclitaxel vs placebo+ paclitaxel | 91 | 92 | PFS | NA | yes | 4 |
| Wolff (HORIZON) | 2013 | Breast cancer | III | mTORC1 | NA | Temsirolimus+letrozole vs placebo+letrozole | 555 | 555 | PFS | OS | no | 5 |
| Yardley | 2015 | Breast cancer | II | mTORC1 | VEGF inhibitor | Everolimus +Paclitaxel+ Bevacizumab vs placebo+ Paclitaxel+ Bevacizumab | 56 | 57 | PFS | OS | no | 4 |
| Armstrong (ASPEN) | 2016 | Renal cell cancer | II | mTORC1 | VEGFR inhibitor | everolimus vs sunitinib | 57 | 51 | PFS | OS | no | 4 |
| Choueiri (METEOR) | 2016 | Renal cell cancer | III | mTORC1 | VEGFR inhibitor | Everolimus vs cabozantinib | 328 | 330 | PFS | OS | no | 4 |
| Cirkel (ROPETAR) | 2016 | Renal cell cancer | II | mTORC1 | VEGFR inhibitor | Everolimus+ pazopanib vs pazopanib | 52 | 49 | PFS | NA | no | 4 |
| Dutcher#a; b | 2009 | Renal cell cancer(a: clear cell cancer; b: no clear cell cancer) | III | mTORC1 | NA | Temsirolimus vs interferon | a: 169; b: 37 | a: 170; b: 18 | OS | PFS | no | 4 |
| Flaherty#a; b; c (ECOG2804) | 2015 | Renal cell cancer | II | mTORC1 | VEGF inhibitors | (a) Bevacizumab plus temsirolimus vs bevacizumab alone (b) Bevacizumab plus temsirolimus vs bevacizumab plus sorafenib (c) Sorafenib plus temsirolimus vs bevacizumab plus sorafenib | a: 80; b: 80; c: 84 | a: 84; b: 83; c: 83 | PFS | NA | no | 4 |
| Hudes#a; b | 2007 | Renal cell cancer | III | mTORC1 | NA | (a) Temsirolimus vs interferon (b) Temsirolimus+ interferon vs interferon | a: 210; b: 209 | a&b: 207 | OS | PFS | no | 4 |
| Hutson | 2013 | Renal cell cancer | III | mTORC1 | VEGF inhibitor |
Temsirolimus vs sorafenib | 259 | 253 | PFS | OS | no | 4 |
| Motzer (RECORD-1) | 2010 | Renal cell cancer | III | mTORC1 | NA | Everolimus vs placebo | 277 | 139 | PFS | OS | no | 5 |
| Motzer (RECORD-3) | 2014 | Renal cell cancer | II | mTORC1 | VEGF inhibitor | Everolimus vs sunitinib | 238 | 233 | PFS | NA | no | 4 |
| Motzer | 2015 | Renal cell cancer | III | mTORC1 | PD-1 inhibitor | Everolimus vs Nivolumab | 410 | 411 | OS | PFS | no | 4 |
| Negrier (TORAVA) | 2011 | Renal cell cancer | II | mTORC1 | VEGF inhibitor | Temsirolimus+ bevacizumab vs interferon alfa + bevacizumab | 88 | 40 | PFS | NA | no | 4 |
| Rini (INTORACT) | 2013 | Renal cell cancer | III | mTORC1 | VEGF inhibitor | Temsirolimus+ bevacizumab vs IFN+ bevacizumab | 400 | 391 | PFS | OS | no | 4 |
| Tannir | 2015 | Renal cell cancer | II | mTORC1 | VEGFR inhibitor | Temsirolimus vs sunitinib | 35 | 33 | PFS | NA | no | 4 |
| Besse | 2014 | Lung cancer | II | mTORC1 | EGFR inhibitor | Everolimus+ erlotinib vs erlotinib | 66 | 67 | DCR | PFS; OS | no | 4 |
| Levy | 2014 | Lung cancer | II | Pan-PI3K | NA | PX-866+ docetaxel vs docetaxel | 48 | 47 | PFS | OS | no | 4 |
| Papadimitrakopoulou (BATTLE-2) | 2016 | Lung cancer | II | AKT | EGFR inhibitor | MK-2206+erlotinib vs erlotinib | 42 | 22 | DCR | PFS; OS | no | 4 |
| Socinski (TAX 326) | 2010 | Lung cancer | II | AKT | NA | Enzastaurin+ carboplatin vs carboplatin | 72 | 74 | TTP | OS | no | 4 |
| Zhu (EVOLVE-1) | 2014 | Liver cancer | III | mTORC1 | NA | Everolimus vs placebo | 362 | 184 | OS | TTP | no | 5 |
| Bendell | 2011 | Colorectal Cancer | II | PI3K/ Akt/mTOR signaling inhibitor | NA | Perifosine+ capecitabine vs placebo + capecitabine | 20 | 18 | TTP | OS | no | 5 |
| Bowles | 2016 | Colorectal Cancer | II | Pan-PI3K | EGFR inhibitor | PX-866 + cetuximab vs placebo+ cetuximab | 42 | 38 | PFS | OS | no | 4 |
| Ohtsu (GRANITE-1) | 2013 | Gastric cancer | III | mTORC1 | NA | Everolimus vs placebo | 439 | 217 | OS | PFS | no | 5 |
| Jimeno | 2015 | Head and neck squamous cell cancer | II | Pan-PI3K | EGFR inhibitor | PX-866+cetuximab vs cetuximab | 42 | 41 | PFS | OS | no | 4 |
| Jimeno | 2016 | Head and neck squamous cell cancer | II | Pan-PI3K | NA | PX-866 + docetaxel vs docetaxel | 42 | 43 | PFS | OS | no | 4 |
| Soulieres (BERIL-1) | 2017 | Head and neck squamous cell cancer | II | Pan-PI3K | NA | Buparlisib + paclitaxel vs placebo + paclitaxel | 79 | 79 | PFS | OS | no | 5 |
| Rachards | 2011 | Pancreatic cancer | II | AKT | NA | Enzastaurin+ gemcitabine vs gemcitabine | 86 | 44 | OS | PFS | no | 4 |
| Pavel (RADIANT-2) | 2011 | Neuroendocrine tumours | III | mTORC1 | NA | Everolimus + octreotide LAR vs placebo+ octreotide LAR | 216 | 213 | PFS | OS | no | 5 |
| Yao (RADIANT-3) | 2011 | Neuroendocrine tumours | III | mTORC1 | NA | Everolimus vs placebo | 207 | 203 | PFS | OS | no | 5 |
| Yao (RADIANT-3) | 2014 | Neuroendocrine tumours | II | mTORC1 | NA | Everolimus vs placebo | 44 | 35 | PFS | OS | no | 5 |
| Yao (RADIANT-4) | 2016 | Neuroendocrine tumours | III | mTORC1 | NA | Everolimus vs placebo | 205 | 97 | PFS | OS | no | 5 |
| Eroglu | 2015 | Sarcoma | II | mTORC1 | RAF/MEK/ERK (MEK1) inhibitor | Temsirolimus + selumetinib vs selumetinib | 35 | 34 | PFS | NA | no | 4 |
| Demetri | 2013 | Sarcoma | III | mTORC1 | NA | Redaforolimus vs placebo | 347 | 364 | PFS | OS | no | 5 |
| Oza | 2015 | Endometrial cancer | II | mTORC1 | NA | Ridaforolimus vs progestin or chemotherapy | 64 | 66 | PFS | OS | no | 4 |
| Wick (EORTC 26082) | 2016 | Glioblastoma | II | mTORC1 | NA | Temsirolimus vs temozolomide | 56 | 55 | OS | PFS | no | 4 |
| Margolin (S0438) | 2012 | Melanoma | II | mTORC1 | VEGFR inhibitor and/or RAF/MEK/ERK inhibitor | Temsirolimus+ sorafenib vs tipifarnib+ sorafenib | 63 | 39 | PFS | OS | no | 4 |
Abbreviation: NR: not reported; NA: not available; PFS: progression-free survival; OS: overall survival; IFN: interferon; ORR: objective response rate; TTP: time to progression; CBR: clinical benefit rate; DCR: Disease control rate; EGFR: epidermal growth factor receptor; VEGFR: vascular endothelial growth factor receptor; mTORC1: mammalian target of rapamycin complex 1.
* Reported a different trial by the previous author in the same year.
# Reported more than one comparation in a trial. Lowercase letter a, b,c means different trial arm in the same study.