Table 1 Clinical evaluation of mTOR inhibitors
mTOR inhibitor | Category | Combination | Cancer type | Phase | Response | PFS (months) | OS (months) | Ref. or trial ID* |
|---|---|---|---|---|---|---|---|---|
Everolimus (RAD001) | Rapalog | None | Thyroid cancer | 2 | No CR/PR; SD (> 24 weeks) 58% | 9 (95% CI 4–14) | 18 (95% CI 7–29) | 200 |
Everolimus | Rapalog | Letrozole | Relapsed ER(+) high-grade ovarian cancer | 2 | CR 0; PR 16%; SD 37% | 3.9 (95% CI 2.8–11); 3-month rate, 47%; 6-month rate, 32% | 13; 6-month OS rate, 84% | 209 |
Everolimus | Rapalog | Exemestrane | ER(+) locally advanced or metastatic breast cancer | 3 | CBR 33.4% vs 18% (control; placebo plus exemestrane) | 6.93 (95% CI 6.44–8.05) vs 2.83 (95% CI 2.74–4.14) (placebo plus exemestrane) | 30.98 (95% CI 27.96–34.56) vs control 26.05 (95% CI 22.57–33.08) | NCT00863655 |
Everolimus | Rapalog | None | Advanced neuroendocine tumor | 3 | Not available | 11.04 (95% CI 8.41–13.86) vs placebo 4.6 (95% CI 3.06–5.49) | 44.02 (95% CI 35.61–51.75) vs placebo 37.68 (95% CI 29.14–45.77) | NCT00510068 |
Everolimus | Rapalog | Rituximab | Diffuse large B cell lymphoma | 2 | ORR 38% (90% CI 21–56%); CR 3/24; PR 6/24 | 2.9 (90% CI 1.8–3.8) | 8.6 (90% CI 4.9–16.3) | 212 NCT00869999 |
MLN0128 | ATP-competitive | Paclitaxel and trastuzumab | Advanced solid tumors | 1 | CR 0; PR 8/54; SD (> 6 months) 6/54 | Not available | Not available | 87 NCT01351350 |
AZD2014 (Vistusertib) | ATP-competitive | None | Metastatic clear cell renal cancer | 2 | Response rate 4% for AZD1024, 13% for everolimus Progressive disease 69% vs 13% for everolimus treatment | 1.8 vs 4.6 for everolimus treatment | 4.9 for AZD1024 | 203 |
Voxtalisib (SAR24540; XL765) | ATP-competitive | None | Relapsed or refractory non-Hodgkin lymphoma or chronic lymphocytic lymphoma | 2 | CR 8/164 (4.9%); PR 22/164 (13.4%); SD 55/164 (33.5%); ORR 18.3% (40.3% for follicular lymphoma) | 1.9 for follicular lymphoma Overall progression-free rate at 24 weeks, 38·6% (95% CI 30·9–46·3) | Not available | 202 NCT01403636 |
Gedatolisib (PKI-587; PF05212384) | ATP-competitive | None | Recurrent endometrial cancer | 2 | CR 1/38 (3%); PR 5/38 (13%); SD > 16 weeks, 24% (37% for stathmin-low cancer, 11% for stathmin-high cancer) | 3.7 (95% CI 2–5.6) for stathmin-low cancer; 3 (95% CI 1.87–5.7) for stathmin-high cancer | Not available | 204 NCT01420081 |