Table 2.
Different PI3K/AKT/mTOR inhibitors under clinical development or approved for clinical use in SOLID tumors.
| Clinical Trial/Author | Year | Tumor | Phase | Target | Protocol | Primary End-Point |
|---|---|---|---|---|---|---|
| Andre (BOLERO-3) | 2014 | Breast | III | mTORC1 | Everolimus + Vinorelbine + trastuzumab vs. placebo + Vinorelbine + trastuzumab | PFS |
| Bachelot (GINECO) | 2012 | Breast | II | mTORC1 | Everolimus + tamoxifen vs. tamoxifen | CBR |
| Baselga (BOLERO-2) ** | 2012 | Breast | III | mTORC1 | Everolimus + exemestane vs. placebo+ exemestane | PFS |
| Baselga (BELLE-2) | 2017 | Breast | III | Pan-PI3K | Buparlisib + fulvestrant vs. placebo+ fulvestrant | PFS |
| Baselga | 2017 | Breast | II | mTORC1 | Ridaforolimus + dalotuzumab + exemestane vs. exemestane | PFS |
| Hurvitz (BOLERO-1) | 2015 | Breast | III | mTORC1 | Everolimus+ Trastuzumab+ Paclitaxel vs. placebo+ Trastuzumab + Paclitaxel | PFS |
| Kim (LOTUS) | 2017 | Breast | II | AKT | Ipatasertib+ paclitaxel vs. placebo+ paclitaxel | PFS |
| Krop (FERGI) | 2016 | Breast | II | Pan-PI3K | Pictilisib+ fulvestrant vs. placebo+ fulvestrant | PFS |
| Martin (BELLE-4) | 2017 | Breast | III | Pan-PI3K | Buparlisib + paclitaxel vs. placebo + paclitaxel | PFS |
| Vuylsteke (PEGGY) | 2016 | Breast | II | Pan-PI3K | Pictilisib+ paclitaxel vs. placebo+ paclitaxel | PFS |
| Wolff (HORIZON) | 2013 | Breast | III | mTORC1 | Temsirolimus + letrozole vs. placebo + letrozole | PFS |
| Yardley | 2015 | Breast | II | mTORC1 | Everolimus +Paclitaxel+ Bevacizumab vs. Placebo + Paclitaxel+ Bevacizumab | PFS |
| Armstrong (ASPEN) | 2016 | RCC | II | mTORC1 | Everolimus vs. sunitinib | PFS |
| Choueiri (METEOR) | 2016 | RCC | III | mTORC1 | Everolimus vs. cabozantinib | PFS |
| Cirkel (ROPETAR) | 2016 | RCC | II | mTORC1 | Everolimus + pazopanib vs. pazopanib | PFS |
| Dutcher#a; b | 2009 | RCC | III | mTORC1 | Temsirolimus vs. interferon (a: cc-RCC; b: non-cc-RCC) |
OS |
| Flaherty#a; b; c (ECOG2804) | 2015 | RCC | II | mTORC1 | (a) Bevacizumab + temsirolimus vs. bevacizumab alone (b) Bevacizumab + temsirolimus vs. bevacizumab + sorafenib (c) Sorafenib + temsirolimus vs. bevacizumab + sorafenib |
PFS |
| Hudes#a; b ** | 2007 | RCC | III | mTORC1 | (a) Temsirolimus vs. interferon (b) Temsirolimus + interferon vs. interferon |
OS |
| Hutson | 2013 | RCC | III | mTORC1 | Temsirolimus vs. sorafenib | PFS |
| Motzer (RECORD-1) ** | 2008 | RCC | III | mTORC1 | Everolimus vs. placebo | PFS |
| Motzer (RECORD-3) | 2014 | RCC | II | mTORC1 | Everolimus vs. sunitinib | PFS |
| Motzer | 2015 | RCC | III | mTORC1 | Everolimus vs. Nivolumab | OS |
| Negrier (TORAVA) | 2011 | RCC | II | mTORC1 | Temsirolimus + bevacizumab vs. INF-α + bevacizumab |
PFS |
| Rini (INTORACT) | 2013 | RCC | III | mTORC1 | Temsirolimus+ bevacizumab vs. IFN + bevacizumab | PFS |
| Tannir | 2015 | RCC | II | mTORC1 | Temsirolimus vs. sunitinib | PFS |
| Besse | 2014 | Lung | II | mTORC1 | Everolimus + erlotinib vs. erlotinib | DCR |
| Levy | 2014 | Lung | II | Pan-PI3K | PX-866+ docetaxel vs. docetaxel | PFS |
| Papadimitrakopoulou (BATTLE-2) | 2016 | Lung | II | AKT | MK-2206+erlotinib vs. erlotinib | DCR |
| Socinski (TAX 326) | 2010 | Lung | II | AKT | Enzastaurin+ carboplatin vs. carboplatin | TTP |
| Zhu (EVOLVE-1) | 2014 | Lung | III | mTORC1 | Everolimus vs. placebo | OS |
| Bendell | 2011 | CRC | II | PI3K/Akt/mTOR pathway | Perifosine + capecitabine vs. placebo + capecitabine | TTP |
| Bowles | 2016 | CRC | II | Pan-PI3K | PX-866 + cetuximab vs. placebo + cetuximab | PFS |
| Ohtsu (GRANITE-1) | 2013 | Gastric cancer | III | mTORC1 | Everolimus vs. placebo | OS |
| Jimeno | 2015 | HNSCC | II | Pan-PI3K | PX-866 + cetuximab vs. cetuximab | PFS |
| Jimeno | 2016 | HNSCC | II | Pan-PI3K | PX-866 + docetaxel vs. docetaxel | PFS |
| Soulieres (BERIL-1) | 2017 | HNSCC | II | Pan-PI3K | Buparlisib + paclitaxel vs. placebo + paclitaxel | PFS |
| Rachards | 2011 | Pancreatic | II | AKT | Enzastaurin + gemcitabine vs gemcitabine | OS |
| Pavel (RADIANT-2) | 2011 | NET | III | mTORC1 | Everolimus + octreotide LAR vs placebo+ octreotide LAR | PFS |
| Yao (RADIANT-3) ** | 2011 | NET | III | mTORC1 | Everolimus vs. placebo | PFS |
| Yao (RADIANT-4) ** | 2016 | NET | III | mTORC1 | Everolimus vs. placebo | PFS |
| Eroglu | 2015 | Sarcoma | II | mTORC1 | Temsirolimus + selumetinib vs. selumetinib | PFS |
| Demetri | 2013 | Sarcoma | III | mTORC1 | Redaforolimus vs. placebo | PFS |
| Oza | 2015 | Endometrial cancer | II | mTORC1 | Ridaforolimusvs progestin or chemotherapy | PFS |
| Wick (EORTC 26082) | 2016 | Glioblastoma | II | mTORC1 | Temsirolimus vs. temozolomide | OS |
| Margolin (S0438) | 2012 | Melanoma | II | mTORC1 | Temsirolimus+ sorafenib vs. tipifarnib+ sorafenib | PFS |
**: Trials leading to product FDA approval; PFS: Progression-free survival; OS: Overall survival; IFN: interferon; TTP: Time to progression; CBR: Clinical benefit rate; DCR: Disease control rate; mTORC1: Mammalian target of rapamycin complex1; RCC: Renal cell carcinoma; cc-RCC: Clear cell-RCC; NET: Neuroendocrine tumor; HNSCC: Head and neck squamous cell carcinoma; CRC: Colorectal cancer.