Supplementary Online Content Rugo HS, Barve A, Waller CF, et al; Heritage Study Investigators. Effect of a proposed trastuzumab biosimilar compared with trastuzumab on overall response rate in patients with ERBB2 (HER2) positive metastatic breast cancer: a randomized clinical trial. JAMA. doi:10.1001/jama.2016.18305 etable. Distribution of Enrolled Patients by Site efigure. Mean Serum Trastuzumab Concentration (ug/ml) vs Time by Treatment (Linear Scale), Pharmacokinetic Population eappendix. List of Heritage Study Investigators This supplementary material has been provided by the authors to give readers additional information about their work.
etable. Distribution of Enrolled Patients by Site Country Site # Patients Randomized PI Name # Sites Per Country # Patients Randomized Per Country South Africa 1501 1 Dreosti, Lydia 7 15 South Africa 1502 4 Maart, Keith South Africa 1504 1 Rens, Daniel South Africa 1505 2 Coccia-Portugal, Maria South Africa 1506 1 Moodley, Shun South Africa 1507 4 Serfontein, Laura South Africa 1508 2 Sherriff, Alicia India 1603 3 Gupta, Mamaraj 16 55 India 1606 2 Kaushal, Ashish India 1609 2 Shah, Pradeep India 1610 4 Patel, Jayanti India 1611 7 Ray, Sirshendu India 1613 4 Coco, Pragna India 1614 1 Sevakumar Pandy, Ananda India 1615 2 Walvekar, Rajesh India 1617 4 Kumar, Anil India 1618 4 Mohite, Saurabh India 1619 1 Gulia, Seema India 1620 9 Gopichand, Mamillapalli India 1622 1 Srinivasan, Sankar India 1624 6 Satheesh, Chiradoni India 1626 3 Radhamadhava, K India 1630 2 Baiju Mon, Balan
Philippines 1901 1 Tamayo, Ma. Belen 9 51 Philippines 1902 3 Lapus, Felycette Gay Philippines 1903 5 Uy, Noemi Philippines 1905 7 Caguioa,Priscilla Philippines 1906 13 Tiambeng, Ma. Luisa A Philippines 1907 3 Tiangco, Beatrice Philippines 1908 13 Parra, Joseph Philippines 1910 4 Fernando, Dr Marie Cherry Lynn Philippines 1911 2 Santos, Paul Dexter Thailand 1701 1 Seetalarom, Col.Kasan 6 47 Thailand 1702 13 Dechaphunkul, Arunee Thailand 1703 3 Dejthevaporn, Thitiya Sirisinha Thailand 1704 13 Akewanlop, Charuwan Thailand 1705 10 Sriuranpong, Virote Thailand 1706 7 Chitapanarux, Imjai Bulgaria 1108 2 Karanikolov, Sotir 1 2 Czech Republic 0201 2 Safanda, Martin 1 2 Georgia 1401 14 Baramidze, Kakhaber 7 62 Georgia 1402 26 Nemsadze, Gia Georgia 1403 2 Janjalia, Mikheil Georgia 1404 3 Kokhreidze, Irakli Georgia 1405 10 Gvamichava, Rema Georgia 1406 3 Jintcharadze, Memed Georgia 1407 4 Dzagnidze, Giorgi Hungary 0501 1 Pinter, Tamas 6 14
Hungary 0502 2 Horvath, Zsolt Hungary 0504 1 Csoszi,Tibor Hungary 0505 5 Lang, Istvan Hungary 0507 3 Piko, Bela Hungary 0513 2 Dank, Magdolna Latvia 4002 5 Plate, Signe 2 6 Latvia 4003 1 Grincuka, Elza Poland 0301 6 Suszko-Kazarnowicz, Malgorzata 8 19 Poland 0302 3 Slowinska, Anna Poland 0303 1 Wronski, Andrzej Poland 0304 1 Mruk, Andrzej Poland 0312 4 Jagiello-Gruszfeld, Agnieszka Poland 0313 1 Radecka, Barbara Poland 0315 1 Litwiniuk, Maria Poland 0316 2 Sarosiek, Tomasz Romania 0809 2 Udrea, Anghel Adrian 6 8 Romania 0810 2 Peltecu, Gheorghe Romania 0812 3 Schenker, Michael Romania 0815 1 Oprean, Cristina Romania 0816 0 Ciurescu, Daniel Romania 0817 0 Mazilu, Laura Russia 1302 5 Shomova, Marina 16 151 Russia 1303 10 Lichinitser, Mikhail Russia 1304 16 Stroyakovsky, Daniil Russia 1305 21 Mukhametshina, Guzel Russia 1307 6 Manzyuk, Liudmila
Russia 1311 9 Krasnojon, Dmitry Russia 1313 12 Poddubskaya, Elena Russia 1315 2 Kopp, Mikhail Russia 1318 28 Manikhas, Alexey Russia 1319 1 Semiglazov, Vladimir Russia 1320 7 Paltuev, Ruslan Russia 1321 7 Lifirenko, Igor Russia 1322 10 Burdaeva, Olga Russia 1323 2 Ledin, Evgeny Russia 1324 13 Gotovkin, Evgeny Russia 1325 2 Galustyan, Anna Serbia 0702 3 Radulovic, Sinisa 2 5 Serbia 0705 2 Kovcin, Vladimir Slovak Republic Slovak Republic 0601 2 Demo, Pavol 2 3 0608 1 Wagnerova, Maria Ukraine 1003 8 Shparyk,Yaroslav 6 55 Ukraine 1004 3 Paramonov, Viktor Ukraine 1005 10 Vynnychenko, Ihor Ukraine 1006 27 Bondarenko, Igor Ukraine 1014 4 Ivashchuk, Oleksandr Ukraine 1016 3 Rusyn, Andriy Chile 2701 1 Salman, Pamela 2 5 Chile 2702 4 Yanez, Eduardo Total 500 97 500
efigure. Mean Serum Trastuzumab Concentration (ug/ml) vs Time by Treatment (Linear Scale), Pharmacokinetic Population Treatment A:Proposed biosimilar B:Trastuzumab.... Only nominal time point with 100 observations per treatment are included in the plot
eappendix. List of Heritage Study Investigators 1. Dr. Mamraj Gupta Apex Hospital PVT LTD, Jaipur, India 2. Dr. Ashish Kaushal HCG Cancer Center, Ahemdabad, India. 3. Dr. Jayanti Patel Apple Hospital, Surat, India 4. Dr. Pradeep Shah M S Patel Cancer Centre, Shree Krishna Hospital, Anand, India 5. Dr. Sirshendu Ray Curie Manavata Cancer Centre, Nashik, India 6. Dr. Pragnya Coca Narayana Hrudayalaya Hospital, Bangalore, India 7. Dr. Rajesh Walvekar Shatabdi Superspeciality Hospital, Nashik, India 8. Dr Anil Kumar M S Ramaiah Medical College and Hospitals, Bangalore, India 9. Dr. Seema Gulia Tata Memorial Hospital, Mumbai, India 10. Dr. Ananda Selvakumar Pandy Pandy Meenakshi Mission Hospital and Research Centre, Madurai, India 11. Dr. Saurabh Mohite Ruby Hall Clinic, Pune, India 12. Dr. Mamillapalli Gopichand City Cancer Center, Andhra Pradesh, India 13. Dr Sankar Srinivasan Apollo Speciality Hospital, Chennai, India 14. Dr Satheesh Triesta Sciences - Clinical Research, Bangalore, India 15. Dr. K.Radha Madhava BGS Global Hospital, Bangalore, India
16. Dr. Baijumon Balan PVS Hospital Pvt. Ltd, Calicut, India 17. Ma. Belen Tamayo, MD Makati Medical Center, Makati City, Philippines 18. Felycette Gay Lapus MD Davao Doctors Hospital, Davao City, Philippines 19. Ma. Noemi Uy, MD Cebu Doctor's University Hospital, Cebu City, Philippines 20. Priscilla Caguioa, MD St Luke's Medical Center, Quezon City, Philippines 21. Ma. Luisa Tiambeng MD Cardinal Santos Medical Center, Manila, Philippines 22. Beatrice Tiangco MD National Kidney and Transplant Institute, Quezon City, Philippines 23. Joseph Parra, MD St. Luke's Medical Center, Taguig City, Philippines 24. Marie Cherry Lynn Fernando MD Manila Doctors Hospital, Manila, Philippines 25. Paul Dexter Santos MD De La Salle Health Sciences Institute, Dasmariñas City, Philippines 26. Col.Kasan Seetalarom Phramaongkutklo Hospital, Bangkok, Thailand 27. Dr. Arunee Dechaphunkul Prince of Songkla University, Unit of Medical Oncology, Hat Yai, Thailand 28. Asst. Prof. Thitiya Sirisinha Dejthevaporn Ramathibodi Hospital, Bangkok, Thailand 29. Asst. Prof. Charuwan Akewanlop Siriraj Hospital, Bangkok, Thailand
30. Asst. Prof.Virote Sriuranpong Chulalongkorn Memorial Hospital, Bangkok, Thailand 31. Asso.Prof. Imjai Chitapanarux Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand 32. Sotir Karanikolov MD Complex Oncology Center, Shumen, Bulgaria 33. Martin Safanda MD Nemocnice na Homolce, Prague, Czech Republic 34. Kakhaber Baramidze MD, PhD. Golden Fleece 21 Century Health House Ltd. Tbilisi, Georgia 35. Prof. Gia Nemsadze Institute of Clinical Oncology, Tbilisi, Georgia 36. Mikheil Janjalia MD Tbilisi Cancer Center, Tbilisi, Georgia 37. Irakli Kokhreidze MD New Vision Univertsity Hospital LTD, Tbilisi, Georgia 38. Prof. Rema Gvamichava Scientific-Research Institute Clinical Medicine, Tbilisi, Georgia 39. Memed Jintcharadze MD. Oncology Center of Adjara, Batumi, Georgia 40. Giorgi Dzagnidze MD, PhD. Khechinashvili University Hospital, Tbilisi, Georgia 41. Dr. Tamás Pintér County Teaching Hospital, Petz Aladár Megyei Oktató Kórház, Gyor, Hungary 42. Dr. Zsolt Horváth University of Debrecen, Medical and Health Science Center Department of Clinical Oncology, Debrecen, Hungary 43. Dr. Tibor Csőszi Jász-Nagykun-Szolnok County Hetényi Géza Hospital, Szolnok, Hungary 44. Prof. Dr. István Láng National Institute of Oncology, Chemotherapy Department, Budapest, Hungary
45. Dr. Béla Pikó Pandy Kalman Hospital of Bekes County Council, Gyula, Hungary 46. Dr. Magdolna Dank Semmelweis University Oncology Center, Budapest, Hungary 47. Dr. Signe Plate Rigas Eastern Clinical University Hospital, Riga, Latvia 48. Dr. Elza Grincuka Daugavpils Regional Hospital, Daugavpils, Latvia 49. Dr. Malgorzata Suszko-Kazarnowicz Olsztyski Osrodek Onkologiczny, Olsztyn, Poland 50. Dr. Anna Slowinska Independent Public Health Department Ministry of Interior Oncology, Olsztyn, Poland 51. Dr. Andrzej Wronski Europejskie Centrum Zdrowia Oncology Dept. Otwock, Poland 52. Dr Andrzej Mruk Centrum Medyczne MrukMedul. Rzeszów, Poland 53. Dr. Jagiello-Gruszfeld NZOZ Onkolmed, Warsaw, Poland 54. Dr.Barbara Radecka SPZOZ Opolskie Centrum Onkologii, Opole, Poland 55. Dr Tomasz Sarosiek NZOZ Magodent. Maciej Sadowski, Warsaw, Poland 56. Dr Maria Litwiniuk Wielkopolskie Centrum Onkologi, Poznań, Poland 57. Dr. Anghel Adrian Udrea MD, PhD. SC Medisprof SRL Cluj-Napoca, Romania 58. Prof. Gheorghe Peltecu MD, PhD. Spitalul Clinic Filantropia, Bucharest, Romania 59. Michael Schenker MD, PhD. Centrul de Oncologie Sfantul Nectarie, Craiova, Romania
60. Cristina Oprean MD. Oncomed SRL, Timişoara, Romania 61. Dr. Mariana Shomova Ryazan Regional Clinical Oncological Dispensary, Ryazan, Russia 62. Prof. Dr. Michail Lichinitser Blokhin Oncological Center, Moscow, Russia 63. Dr, Danilil Stroyakovsky City Clinical Oncology Hospital, Stepanovskoye, Russia 64. Dr. Guzel Mukhametshina Regional Clinical Oncological Center, Kazan, Russia 65. Dr. Lyudmila Manzuk Blokhin Oncological Center, Moscow, Russia 66. Dr. Dmitriy Krasnozhon Leningrad Regional Oncology Center, Leningrad, Russia 67. Dr. Elena Poddubskaya Blokhin Oncological Center, Moscow, Russia 68. Dr. Anna Tarasova Samara Regional Clinical Oncology Center Samara, Russia 69. Dr. Alexey Manikhas City Clinical Oncology Dispansery, Saint Petersburg, Russia 70. Prof. Dr. Vladimir Semiglazov Petrov Research Institute of Oncology, Kursk, Russia 71. Dr. Ruslan Paltuev Railway Clinical Hospital, Oncology Department, St Petersburg, Russia 72. Dr. Igor Lifirenko Kursk Regional Oncology Center, Kursk, Russia 73. Dr. Olga Burdaeva Arkhangelsk Regional Oncology Center, Arkhangelsk, Russia 74. Dr. Evgenii Ledin Treatment and Rehabilitation Center, Moscow, Russia
75. Dr. Evgeny Gotovkin Ivanovo Regional Oncology Center, Ivanovo Oblast, Russia 76. Dr. Anna Galustyan Oncology center of Moscow district, Saint-Petersburg, Russia 77. Prof. Sinisa Radulovic Institute for Oncology and Radiology of Serbia, Belgrade, Serbia 78. Dr. Vladimir Kovcin Clinical Hospital Center, Belgrade, Serbia 79. Dr. Pavol Demo Fakultna nemocnica s poliklinikou, Nove Zamky, Slovakia 80. Dr. Maria Wagnerova Vychodoslovensky onkologicky ustav, Kosice, Slovakia 81. Prof. Lydia Dreosti MBBCh Department of Medical Oncology, University of Pretoria and Steve Biko Academic Hospitals, Pretoria, South Africa 82. Keith Maart MBChB Langenhoven Drive Oncology Centre, Port Elizabeth, South Africa 83. Daniel Rens MBChB Vaal Triangle Oncology, Vereeniging, South Africa 84. Dr Maria Coccia Portugal Eastleigh Breast Care Centre, Lynnwood, Pretoria, Gauteng, South Africa 85. Shun Moodley MBBCh Wits Clinical Research, Johannesburg, South Africa. 86. Dr. Laura Serfontein MBChB, MMed GVI Oncology Cape Gate Clinical Trial Centre, Cape Town, South Africa 87. Dr. Alicia Sherriff MBChB Department of Oncotherapy Universitas Annex National Hospital Grounds, Bloemfontein, South Africa 88. Yaroslav Shparyk MD, Phd. Lviv State Oncological Regional Treatment-Diagnostics Center, Lviv, Ukraine 89. Dr. Victor Paramonov Cherkassy Regional Oncology Dispensary, Cherkassy, Ukraine
90. Ihor Vynnychenko MD, PhD Sumy Regional Oncology Center, Sumy, Ukraine 91. Prof. Igor Bondarenko MD, PhD Dnipropetrovsk State Medical Academy, Dnipropetrovsk, Ukraine 92. Prof. Olexsandr Ivashchuk MD, PhD Chernivtsi Regional Oncology Center, Chernivtsi, Ukraine 93. Prof. Andriy Rusyn MD, PhD Zakarpattya Regional Clinical Oncological Dispensary, Uzhgorod, Ukraine 94. Pamela Salman MD Fundacion Arturo Lopez Perez, Santiago, Chile 95. Eduardo Yanez MD Instituto Clinico Oncologico del Sur, Temuco, Chile