Yao et al 2008 II GEP, thymus, Everolimus 5mg 60 ORR 20% 22% PR, 60 weeks 1 yr 83% – (18) lung, renal or 10mg + 70% SD, 8% PD 2 yr 81% – octreotide LAR 3 yr 78% – RADIANT-I *= primary endpoint PR = Partial response; SD = stable disease; PD = progressive disease; CGA = chromogranin A; ORR = objective response rate; OS = overall survival; PFS = progression-free survival; pts = patients 4 Examples of reported phase III trials involving everolimus in patients with lung, – gastroenteropancreatic, and other neuroendocrine tumors Authors Year type Regimen Number of Objective response PFS (months) patients Yao et al (44) 2015 Advanced Everolimus 1mg vs 302 52% risk reduction for 11.0 vs 3.9 (central nonfunctional placebo progression or death review (RADIANT IV) lung and GI 14.0 vs 5.5 NETs (investigator review) Anthony et al 2015 Functional Everolimus 10mg + 429 (339 No sig difference in PFS O+E+SSA 14.3 (40) advanced octreotide vs placebo previous SSA relating to SSA O+E 25.2 NETs + octreotide. exposure) (RADIANT-II Comparison of P+O+SSA 11.1 sub-analysis) previous SSA P+O 13.6 exposure with none 2015 Pancreatic Everolimus vs placebo 410 (204 = ORR 4.8% vs 2% in prior Prior chemo 11 vs 3.2 et al comparing prior 50% were chemo, 4.9% vs 2% in Chemotherapy-naïve (80) chemo with chemo-naïve) chemo-naïve 11 vs 5.4 * (RADIANT-3 sub-group) Castellano et 2013 Colorectal Everolimus + 39 66% risk reduction for 29.9 vs 6.6 * al (41) octreotide vs placebo progression (RADIANT-II + octreotide sub group analysis) Fazio et al 2013 Lung Everolimus + 44 28% risk reduction for 13.63 vs 5.59 * (42) octreotide vs placebo progression (RADIANT-II + octreotide
Yao et al (18) RADIANT-I 2008 II GEP, thymus, lung, renal Everolimus 5mg or 10mg + octreotide LAR 60 ORR 20% 22% PR, 70% SD, 8% PD 60 weeks 1 yr – 83% 2 yr – 81% 3 yr – 78% *= primary endpoint PR = Partial response; SD = stable disease; PD = progressive disease; CGA = chromogranin A; ORR = objective response rate; OS = overall survival; PFS = progression-free survival; pts = patients 4 – Examples of reported phase III trials involving everolimus in patients with lung, gastroenteropancreatic, and other neuroendocrine tumors Authors Year type Regimen Number of patients Objective response PFS (months) Yao et al (44) (RADIANT IV) 2015 Advanced nonfunctional lung and GI NETs Everolimus 1mg vs placebo 302 52% risk reduction for progression or death 11.0 vs 3.9 (central review 14.0 vs 5.5 (investigator review) Anthony et al (40) (RADIANT-II sub-analysis) 2015 Functional advanced NETs Everolimus 10mg + octreotide vs placebo + octreotide. Comparison of previous SSA exposure with none 429 (339 previous SSA exposure) No sig difference in PFS relating to SSA O+E+SSA 14.3 O+E 25.2 P+O+SSA 11.1 P+O 13.6 et al (80) (RADIANT-3 sub-group) 2015 Pancreatic Everolimus vs placebo comparing prior chemo with 410 (204 = 50% were chemo-naïve) ORR 4.8% vs 2% in prior chemo, 4.9% vs 2% in chemo-naïve Prior chemo 11 vs 3.2 Chemotherapy-naïve 11 vs 5.4 * Castellano et al (41) (RADIANT-II sub group analysis) 2013 Colorectal Everolimus + octreotide vs placebo + octreotide 39 66% risk reduction for progression 29.9 vs 6.6 * Fazio et al (42) (RADIANT-II 2013 Lung Everolimus + octreotide vs placebo + octreotide 44 28% risk reduction for progression 13.63 vs 5.59 *
2016_07_29_Future_Oncology_Everolimus_review_manuscript.docx