Table 3 Examples of reported phase I and II trials of everolimus in patients with – gastroenteropancreatic and lung neuroendocrine tumors Authors Year Phase Primary tumor Regimen Number Response PFS Median location of assessment OS patients (months) Chan et al 2013 I Carcinoid (small Sorafenib + 21 1 PR, 13 SD, 3 PD. 79% at 6 - (35) bowel, bronchus, everolimus 62% disease months unknown shrinkage. 26% CGA primary) or decrease. pancreatic Chan et al 2012 I Carcinoid Pasireotide + 22 90% SD, 81% some 76% at 6 - (36) bowel, bronchus, everolimus degree of tumor months unknown shrinkage. 21% CGA 65% at 12 primary) or decrease. months pancreatic Chan et al 2013 I/II 1/2 Everolimus 5mg 43 16 (40%) PR, 53% SD, 15.4 * Not (79) pancreatic or 10mg + 7% PD. 45% CGA reached temozolomide decrease. Kulke et al 2015 II Pancreatic Everolimus + 150 Response rate 31% 16.7 vs OS 36.7 vs (39) octreotide vs vs 12% 14 * 35.0 everolimus + bevacizumab + octreotide Yao J et al 2014 II Pancreatic Everolimus vs 79 72% risk reduction 15.47 vs Not (38) placebo 4.29* reached Bajetta et 2014 II GEP + lung Everolimus + 50 18% ORR * Not Not al (37) octreotide LAR reached reached 2% CR, 16% PR, 74% first line by 277 by 277 SD, 6% PD days days Yao et al 2010 II Pancreatic Everolimus in 160 9.6% (Radiological 9.7, 8.5 OS 24.9 – (61) octreotide naïve assessment), 10.4% pts (stratum 1) (Ix assessment )ORR* 16.7, 15.2 24month Everolimus + 4.4% (radiological survival octreotide - pts assessment), 11.1 54.7% on octreotide (investigator for 3/12 assessment ) ORR (stratum 2)
Table 3 – Examples of reported phase I and II trials of everolimus in patients with gastroenteropancreatic and lung neuroendocrine tumors Authors Year Phase Primary tumor location Regimen Number of patients Response assessment PFS Median OS (months) Chan et al (35) 2013 I Carcinoid (small bowel, bronchus, unknown primary) or pancreatic Sorafenib + everolimus 21 1 PR, 13 SD, 3 PD. 62% disease shrinkage. 26% CGA decrease. 79% at 6 months - Chan et al (36) 2012 I Carcinoid bowel, bronchus, unknown primary) or pancreatic Pasireotide + everolimus 22 90% SD, 81% some degree of tumor shrinkage. 21% CGA decrease. 76% at 6 months 65% at 12 months - Chan et al (79) 2013 I/II 1/2 pancreatic Everolimus 5mg or 10mg + temozolomide 43 16 (40%) PR, 53% SD, 7% PD. 45% CGA decrease. 15.4 * Not reached Kulke et al (39) 2015 II Pancreatic Everolimus + octreotide vs everolimus + bevacizumab + octreotide 150 Response rate 31% vs 12% 16.7 vs 14 * OS 36.7 vs 35.0 Yao J et al (38) 2014 II Pancreatic Everolimus vs placebo 79 72% risk reduction 15.47 vs 4.29* Not reached Bajetta et al (37) 2014 II GEP + lung Everolimus + octreotide LAR first line 50 18% ORR * 2% CR, 16% PR, 74% SD, 6% PD Not reached by 277 days Not reached by 277 days Yao et al (61) 2010 II Pancreatic Everolimus in octreotide naïve pts (stratum 1) Everolimus + octreotide - pts on octreotide for 3/12 (stratum 2) 160 9.6% (Radiological assessment), 10.4% (Ix assessment )ORR* 4.4% (radiological assessment), 11.1 (investigator assessment ) ORR 9.7, 8.5 16.7, 15.2 OS – 24.9 24month survival 54.7%
2016_07_29_Future_Oncology_Everolimus_review_manuscript.docx