Published Data in Intrahepatic Cholangiocarcinoma The following tables summarize the prospective and retrospective studies on the use of SIR-Spheres Y-90 resin microspheres in the treatment of intrahepatic cholangiocarcinoma. Tumor response and/or survival results are listed accordingly. For studies in which multiple tumor types were investigated, outcomes include all tumor types, unless otherwise noted. Prospective studies Median Survival Treatment/Line of Therapy Median survival N (n) ORRa SDa From Treatment Reference (n) from diagnosis (or PFS) SIR-Spheresb ≥1st line (45); 61 nr nr PFS: 2.8 mo 8.7 mo White, 2019 TheraSpherec ≥1st line (16) SIR-Spheres 1st line (2) 82.3% 17.6% 17 14.8 mod,e nr Filippi, 2015 SIR-Spheres ≥2nd line (15) (PET) (PET) 21 0%; SIR-Spheres ≥2nd line (21) nr 16.3 mo nr Camacho, 2014 37.5%, (mRECIST) SIR-Spheres ≥2nd line (19) 19 11% 68% 11.5 mo 25.1 mo Rafi, 2013 SIR-Spheres 1st line (6); SIR-Spheres ≥2nd line (20); 23 22% 65% 11.7 mo 36.6 mo Haug, 2011 follow-up MRI available for 23 patients SIR-Spheres 1st line (6); 25 24% 48% 9.3 mo 20.4 mo Saxena, 2010 SIR-Spheres 2nd line (19) Retrospective studies Median Survival Treatment/Line of Therapy Median survival N (n) ORRa SD From Treatment Reference (n) from diagnosis (or PFS) SIR-Spheres ≥2nd line 9 100%c nr 16.5±1.4 mo nr Filippi, 2019 SIR-Spheres 1st line PFS: 2.4 mo (2 HCC-CC, 13 HCC); 154; mRECIST: mRECIST: (HCC-CC); TheraSphere 1st line 14.5 mo HCC-CC (10), 30% (HCC-CC) 30% (3/10 HCC-CC) 7.4 mo (HCC; (4 HCC); (HCC-CC); Huang, 2019 HCC (124), 71% (HCC; P=0.02) 24% (26/107 HCC) P <0.0001); Y-90 microspheres, nr (HCC and PSM HCC (20) 50% (PSM HCC; 35% (7/20 PSM 6.0 mo unspecified type (3 PSM PSM HCC) P=0.35) HCC) (PSM HCC; HCC) P=0.017) Other LRTs 1st line SIR-Spheres >1st line (58) 58 nr nr nr 10.3 mo Levillain, 2019 All tumor types (38) 11.1% (PR; HCC HCC (23); group) 83.3% (HCC group) NETLM (7); 42.9% (PR; non- 57.1% (non-HCC 14.4 mo (HCC CRCLM (3); HCC group) group) group) SIR-Spheres ≥2nd line (38) ICC (2); 0% (PR, qEASL; 94.4% (qEASL; HCC nr Schobert, 2019 19.0 mo (non- melanoma LM (1); HCC group) group) HCC group) prostate cancer 28.6% (PR, 71.4% (qEASL; LM (1); qEASL; non-HCC non-HCC group) leiomyosarcoma group) LM (1) SIR-Spheres 1st line (21) 21 4.8% (PR) 42.9% nr 15.0 mo Reimer, 2018 Median Survival Treatment/Line of Therapy Median survival N (n) ORRa SD From Treatment Reference (n) from diagnosis (or PFS) 33.6 mo SIR-Spheres and SIR-Spheres ≥1st line (9) TheraSphere or 17 nr nr nr Shaker, 2018 PFS: 15.6 mo TheraSphere ≥1st line (8) SIR-Spheres; 2.4 mo TheraSphere All tumor types SIR-Spheres ≥1st line (366) 366f nr nr 11.4 mo nr Ingrisch, 2017 CC (35) SIR-Spheres 2nd line (24) 24 36.4% (PR) 45.5% 9.0 mo 24.0 mo Jia, 2017 All tumor types 389 Total 11.7 mog; CRCLM (136); CRCLM 9.1 mo; HCC (66); HCC 12.7 mo; SIR-Spheres ≥2nd line (389) NETLM (56); 22% 41% NETLM na; nr Paprottka, 2017 BCLM (40); BCLM 7.5 mo; CC (35); CC 14.1 mo; LM from other other nr cancers (56) 9.1 mo SIR-Spheres SIR-Spheres ≥1st line (17) 11.5% 61.5% and or 26.1 mo 29 PR, SIR-Spheres SIR-Spheres TheraSphere TheraSphere ≥1st line (12); SIR-Spheres and Swinburne, 2017 and TheraSphere and TheraSphere 7.5 mo SIRT 1st line (8); TheraSphere SIR-Spheres; SIRT ≥2nd line (21) 13.9 mo TheraSphere SIR-Spheres 1st line (4); 15%; 30%; 23 17.9 mo nr Mosconi, 2016 ≥2nd line (19) 45% (mRECIST) 15% (mRECIST) SIR-Spheres 1st line (4); 16 31% nr 9.6 mog nr Soydal, 2016 SIR-Spheres 2nd line (12) SIR-Spheres ≥2nd line (33) 33 36.4% 51.5% 22.0 mo 43.7 mo Hoffmann, 2012 In an effort to facilitate the review of data in this table, data originally reported as days/weeks were converted to months. BCLM: breast cancer liver metastases; CC: cholangiocarcinoma (as defined by the study authors); CRCLM: colorectal cancer liver metastases; HCC: hepatocellular carcinoma; HCC-CC: hepatocellular carcinoma-cholangiocarcinoma; ICC: intrahepatic cholangiocarcinoma (as defined by the study authors); LM: liver metastases; LRT: locoregional therapy; mo: months; mRECIST: modified Response Evaluation Criteria In Solid Tumors; n/a: not applicable; NETLM: neuroendocrine tumor liver metastases; nr: not reported; ORR: objective response rate (complete response [CR] + partial response [PR]); PERCIST: Positron Emission Tomography Response Criteria In Solid Tumors; PFS: progression- free survival; PR: partial response evaluated only; PSM: propensity score–matched; qEASL: Quantitative European Association for the Study of the Liver criteria; SD: stable disease; SIRT: selective internal radiation therapy. a. By RECIST unless otherwise indicated. b. SIR-Spheres Y-90 resin microspheres. c. TheraSphere Yttrium-90 Glass Microspheres. d. By PERCIST. e. Months calculated from weeks using Google calculator: 1 week = 0.230137 months. f. Data represent a subset of data from Paprottka 2017. g. Months calculated from days using Google calculator: 1 day = 0.0328767 months. References: 1. White J et al. J Vasc Interv Radiol 2019; 30: 1185–1192. 2. Filippi L et al. Nucl Med Biol 2015; 42: 59–64. 3. Camacho JC et al. J Vasc Interv Radiol 2014; 25: 256–265. 4. Rafi S et al. Cardiovasc Intervent Radiol 2013; 36: 440–448. 5. Haug AR et al. Eur J Nucl Med Mol Imaging 2011; 38: 1037–1045. 6. Saxena A et al. Ann Surg Oncol 2010; 17: 484–491. 7. Filippi L et al. Cancer Biother Radiopharm. Published online: February 13, 2019. (doi:10.1089/cbr.2018.2718). 8. Huang YH et al. J Vasc Interv Radiol 2019; 30: 1317–1324. 9. Levillain H et al. Eur J Nucl Med Mol Imaging 2019; 46: 2270–2279. 10. Schobert I et al. J Nucl Med Published Online: January 17, 2019. (doi:10.2967/jnumed.118.219691). 11. Reimer P et al. Cardiovasc Intervent Radiol Published Online: January 17, 2018. (doi:10.1007/s00270-017-1871-2). 12. Shaker TM et al. Am J Surg Published Online: February 2, 2018. (doi:10.1016/j.amjsurg.2017.11.022). 13. Ingrisch M et al. J Nuc Med Published Online: November 16, 2017.(doi:10.2967/jnumed.117.200758). 14. Jia Z et al. J Cancer Res Clin Oncol 2017; 143: 481–489. 15. Paprottka KJ et al. Eur J Nucl Med Mol Imaging 2017; 44: 1185–1193. 16. Swinburne NC et al. Cancer Biother Radiopharm 2017; 32: 161–168. 17. Mosconi C et al. Br J Cancer 2016; 115: 297–302. 18. Soydal C et al. Ann Nucl Med 2016; 30: 29–34. 19. Hoffmann RT et al. Cardiovasc Intervent Radiol 2012; 35: 105–116. SIR-Spheres® is a registered trademark of Sirtex SIR-Spheres Pty Ltd Sirtex Medical Europe GmbH Last update with data identified through September 30, 2019. Joseph-Schumpeter-Allee 33, 53227 Bonn, Germany 219-EUA-0919 www.sirtex.com.