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Annual Report 2017

Division of Experimental Therapeutics

[Kashiwa Campus] Toshihiko Doi, Kiyotaka Yoh, Yoichi Naito, Takahiro Kogawa, Kohei Shitara, Hideaki Takahashi, Yasutoshi Kuboki[Tsukiji Campus] Noboru Yamamoto, Toshio Shimizu, Yutaka Fujiwara, Kan Yonemori, Kiyoshi Yoshimura, Shigehisa Kitano, Shunsuke Kondo, Satoru Iwasa, Akihiko Shimomura, Takafumi Koyama, Takahiro Ebata

Introduction

The Division of Experimental Therapeutics supports efforts toward the creation of new drugs and other products from breakthroughs originating from academic institutions by achieving results at the level of basic research. We evaluate and discover excellent research and development proposals, and provide integrated management of the program so that basic research outcomes are linked to clinical research and clinical trial for approval. We have conducted several investigator initiated trials (IITs) as applications for approval and also have promoted research and development in the field of medicine.

Our team and what we do

This division plays a key role of the new anti-cancer drug development in Japan as well as in Asia. The top priority is to conduct first in human (FIH) trials, and we also perform phase I trials for solid tumors (i.e., all comers). Recently, we have been joining global phase I trials to accelerate the new drug development in Japan. Web- or tel.-conferences are held with the EU and US sites, and we discuss about the patient enrollment as well as the further developmental strategy. Routine web-conferences are also held between the National Cancer Center (NCC)-Hospital Tokyo) and the NCC-Hospital East (Kashiwa) every Friday morning, and we are sharing information about adverse events, patient enrollment, and are referring candidates each other to accelerate enrollment.

Research activities

We promote the following activities for appropriate conducting of clinical research and trials.

To plan the clinical trial as IIT for achieving proof of concept (POC) of new academic seeds
Explanation meetings for researchers and office employees on compliance of laws, ordinances and guidelines
To consider development design to create novelty with the goal of creating innovative drugs, medical devices, as well as ensuring that research projects on promising results proceed more rapidly and in greater depth

List of papers published in January 2017 - March 2018

Journal

1. Doi T, Hamaguchi T, Shitara K, Iwasa S, Shimada Y, Harada M, Naito K, Hayashi N, Masada A, Ohtsu A. NC-6004 Phase I study in combination with gemcitabine for advanced solid tumors and population PK/PD analysis. Cancer Chemother Pharmacol, 79:569-578, 2017

2. Yoshino T, Uetake H, Tsuchihara K, Shitara K, Yamazaki K, Oki E, Sato T, Naitoh T, Komatsu Y, Kato T, Yamanaka K, Iwasaki K, Soeda J, Hihara M, Yamanaka T, Ochiai A, Muro K. Rationale for and Design of the PARADIGM Study: Randomized Phase III Study of mFOLFOX6 Plus Bevacizumab or Panitumumab in Chemotherapy-naive Patients With RAS (KRAS/NRAS) Wild-type, Metastatic Colorectal Cancer. Clin Colorectal Cancer, 16:158-163, 2017

3. Masuda H, Qi Y, Liu S, Hayashi N, Kogawa T, Hortobagyi GN, Tripathy D, Ueno NT. Reverse phase protein array identification of triple-negative breast cancer subtypes and comparison with mRNA molecular subtypes. Oncotarget, 8:70481-70495, 2017

4. Tsuruoka K, Horinouchi H, Goto Y, Kanda S, Fujiwara Y, Nokihara H, Yamamoto N, Asakura K, Nakagawa K, Sakurai H, Watanabe SI, Tsuta K, Ohe Y. PD-L1 expression in neuroendocrine tumors of the lung. Lung Cancer, 108:115-120, 2017

5. Sekine I, Harada H, Yamamoto N, Wakabayashi M, Murakami H, Goto K, Nogami N, Seto T, Oshita F, Okamoto H, Tanaka H, Tamura T, Ishikura S, Ohe Y. Randomized phase II trial of weekly dose-intensive chemotherapy or amrubicin plus cisplatin chemotherapy following induction chemoradiotherapy for limited-disease small cell lung cancer (JCOG1011). Lung Cancer, 108:232-237, 2017

6. Niho S, Ohe Y, Ohmatsu H, Umemura S, Matsumoto S, Yoh K, Goto K. Switch maintenance chemotherapy using S-1 with or without bevacizumab in patients with advanced non-small cell lung cancer: a phase II study. Lung Cancer, 108:66-71, 2017

7. Miyoshi T, Umemura S, Matsumura Y, Mimaki S, Tada S, Makinoshima H, Ishii G, Udagawa H, Matsumoto S, Yoh K, Niho S, Ohmatsu H, Aokage K, Hishida T, Yoshida J, Nagai K, Goto K, Tsuboi M, Tsuchihara K. Genomic Profiling of Large-Cell Neuroendocrine Carcinoma of the Lung. Clin Cancer Res, 23:757-765, 2017

8. Sakai D, Chung HC, Oh DY, Park SH, Kadowaki S, Kim YH, Tsuji A, Komatsu Y, Kang YK, Uenaka K, Wijayawardana SR, Wacheck V, Wang X, Yamamura A, Doi T. A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian patients with MET diagnostic positive, advanced gastric cancer. Cancer Chemother Pharmacol, 80:1197-1207, 2017

9. Bando H, Rubinstein L, Harris P, Yoshino T, Doi T, Ohtsu A, Welch J, Takebe N. Analysis of esophagogastric cancer patients enrolled in the National Cancer Institute Cancer Therapy Evaluation Program sponsored phase 1 trials. Gastric cancer, 20:481-488, 2017

10. Yoshida A, Kobayashi E, Kubo T, Kodaira M, Motoi T, Motoi N, Yonemori K, Ohe Y, Watanabe SI, Kawai A, Kohno T, Kishimoto H, Ichikawa H, Hiraoka N. Clinicopathological and molecular characterization of SMARCA4-deficient thoracic sarcomas with comparison to potentially related entities. Mod Pathol, 30:797-809, 2017

11. Saka H, Kitagawa C, Kogure Y, Takahashi Y, Fujikawa K, Sagawa T, Iwasa S, Takahashi N, Fukao T, Tchinou C, Landers D, Yamada Y. Safety, tolerability and pharmacokinetics of the fibroblast growth factor receptor inhibitor AZD4547 in Japanese patients with advanced solid tumours: a Phase I study. Invest New Drugs, 35:451-462, 2017

12. Shitara K, Kim TM, Yokota T, Goto M, Satoh T, Ahn JH, Kim HS, Assadourian S, Gomez C, Harnois M, Hamauchi S, Kudo T, Doi T, Bang YJ. Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer. Oncotarget, 8:79546-79555, 2017

13. Taniguchi H, Iwasa S, Yamazaki K, Yoshino T, Kiryu C, Naka Y, Liew EL, Sakata Y. Phase 1 study of OCV-C02, a peptide vaccine consisting of two peptide epitopes for refractory metastatic colorectal cancer. Cancer Sci, 108:1013-1021, 2017

14. Ohue M, Iwasa S, Kanemitsu Y, Hamaguchi T, Shiozawa M, Ito M, Yasui M, Katayama H, Mizusawa J, Shimada Y. A Phase II/III randomized controlled trial comparing perioperative versus postoperative chemotherapy with mFOLFOX6 for lower rectal cancer with suspected lateral pelvic node metastasis: Japan Clinical Oncology Group Study JCOG1310 (PRECIOUS study). Jpn J Clin Oncol, 47:84-87, 2017

15. Nishikawa T, Matsumoto K, Tamura K, Yoshida H, Imai Y, Miyasaka A, Onoe T, Yamaguchi S, Shimizu C, Yonemori K, Shimoi T, Yunokawa M, Xiong H, Nuthalapati S, Hashiba H, Kiriyama T, Leahy T, Komarnitsky P, Fujiwara K. Phase 1 dose-escalation study of single-agent veliparib in Japanese patients with advanced solid tumors. Cancer Sci, 108:1834-1842, 2017

16. Shitara K. Chemotherapy for advanced gastric cancer: future perspective in Japan. Gastric cancer, 20:102-110, 2017

17. Sakaida E, Ebata T, Iwasawa S, Kurimoto R, Yonemori S, Ota S, Nakatani Y, Sekine I, Takiguchi Y. Potential Activity of Amrubicin as a Salvage Therapy for Merkel Cell Carcinoma. Intern Med, 56:567-570, 2017

18. Shimomura A, Kondo S, Kobayashi N, Iwasa S, Kitano S, Tamura K, Fujiwara Y, Yamamoto N. Do all patients in the phase I oncology trials need to be hospitalized? Domestic but outstanding issues for globalization of drug development in Japan. Int J Clin Oncol, 22:780-785, 2017

19. Makita S, Yoshimura K, Tobinai K. Clinical development of anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma. Cancer Sci, 108:1109-1118, 2017

20. Hisakane K, Ohmatsu H, Umemura S, Kirita K, Matsumoto S, Yoh K, Niho S, Goto K. Efficacy of Cell-Free and Concentrated Ascites Reinfusion Therapy for Palliative Care in a Patient with Malignant Pleural Mesothelioma: A Case Report. J Nippon Med Sch, 84:231-236, 2017

21. Yoh K, Goto Y, Naito Y, Kishi K, Mori K, Hotta K, Hosomi Y, Yamada K, Tanai C, Tomizawa Y, Inoue A, Hasegawa Y, Nishio M, Ohashi Y, Kunitoh H. Impact of Maintenance Therapy for Patients with Non-small Cell Lung Cancer in a Real-world Setting. Anticancer Res, 37:1507-1513, 2017

22. Kudo T, Hamamoto Y, Kato K, Ura T, Kojima T, Tsushima T, Hironaka S, Hara H, Satoh T, Iwasa S, Muro K, Yasui H, Minashi K, Yamaguchi K, Ohtsu A, Doki Y, Kitagawa Y. Nivolumab treatment for oesophageal squamous-cell carcinoma: an open-label, multicentre, phase 2 trial. Lancet Oncol, 18:631-639, 2017

23. Takamochi K, Takahashi F, Suehara Y, Sato E, Kohsaka S, Hayashi T, Kitano S, Uneno T, Kojima S, Takeuchi K, Mano H, Suzuki K. DNA mismatch repair deficiency in surgically resected lung adenocarcinoma: Microsatellite instability analysis using the Promega panel. Lung Cancer, 110:26-31, 2017

24. Ikemura S, Aramaki N, Fujii S, Kirita K, Umemura S, Matsumoto S, Yoh K, Niho S, Ohmatsu H, Kuwata T, Kojima M, Ochiai A, Betsuyaku T, Tsuboi M, Goto K, Ishii G. Changes in the tumor microenvironment during lymphatic metastasis of lung squamous cell carcinoma. Cancer Sci, 108:136-142, 2017

25. Imaoka H, Sasaki M, Takahashi H, Hashimoto Y, Ohno I, Mitsunaga S, Watanabe K, Umemoto K, Kimura G, Suzuki Y, Ikeda M. Progression-free survival as a surrogate endpoint in advanced neuroendocrine neoplasms. Endocr Relat Cancer, 24:475-483, 2017

26. Okuyama H, Ikeda M, Takahashi H, Ohno I, Hashimoto Y, Mitsunaga S, Sakamoto Y, Kondo S, Morizane C, Ueno H, Kobayashi T, Arai Y, Okusaka T. Transarterial (Chemo)Embolization for Liver Metastases in Patients with Neuroendocrine Tumors. Oncology, 92:353-359, 2017

27. Kurimoto R, Ebata T, Iwasawa S, Ishiwata T, Tada Y, Tatsumi K, Takiguchi Y. Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma. Oncology letters, 14:944-950, 2017

28. Kojima T, Doi T. Immunotherapy for Esophageal Squamous Cell Carcinoma. Curr Oncol Rep, 19:33, 2017

29. Makise N, Yoshida A, Komiyama M, Nakatani F, Yonemori K, Kawai A, Fukayama M, Hiraoka N. Dedifferentiated Liposarcoma With Epithelioid/Epithelial Features. Am J Surg Pathol, 41:1523-1531, 2017

30. Watanabe S, Takashima A, Taniguchi H, Tanaka Y, Nakamura S, Okita N, Honma Y, Iwasa S, Kato K, Hamaguchi T, Boku N. Esophageal Metastasis from Rectal Cancer Successfully Treated with Fluorouracil-Based Chemotherapy with Bevacizumab: A Case Report and Review of the Literature. Case Rep Oncol, 10:407-415, 2017

31. Shoji H, Tada K, Kitano S, Nishimura T, Shimada Y, Nagashima K, Aoki K, Hiraoka N, Honma Y, Iwasa S, Takashima A, Kato K, Boku N, Honda K, Yamada T, Heike Y, Hamaguchi T. The peripheral immune status of granulocytic myeloid-derived suppressor cells correlates the survival in advanced gastric cancer patients receiving cisplatin-based chemotherapy. Oncotarget, 8:95083-95094, 2017

32. Yamamoto N, Fujiwara Y, Tamura K, Kondo S, Iwasa S, Tanabe Y, Horiike A, Yanagitani N, Kitazono S, Inatani M, Tanaka J, Nishio M. Phase Ia/Ib study of the pan-class I PI3K inhibitor pictilisib (GDC-0941) administered as a single agent in Japanese patients with solid tumors and in combination in Japanese patients with non-squamous non-small cell lung cancer. Invest New Drugs, 35:37-46, 2017

33. Yamamoto N, Goto K, Nishio M, Chikamori K, Hida T, Maemondo M, Katakami N, Kozuki T, Yoshioka H, Seto T, Tajima K, Tamura T. Final overall survival in JO22903, a phase II, open-label study of first-line erlotinib for Japanese patients with EGFR mutation-positive non-small-cell lung cancer. Int J Clin Oncol, 22:70-78, 2017

34. Yamamoto N, Goto K, Nishio M, Chikamori K, Hida T, Maemondo M, Katakami N, Kozuki T, Yoshioka H, Seto T, Tajima K, Tamura T. Erratum to: Final overall survival in JO22903, a phase II, open-label study of first-line erlotinib for Japanese patients with EGFR mutation-positive non-small-cell lung cancer. Int J Clin Oncol, 22:79, 2017

35. Shitara K, Chin K, Yoshikawa T, Katai H, Terashima M, Ito S, Hirao M, Yoshida K, Oki E, Sasako M, Emi Y, Tsujinaka T. Phase II study of adjuvant chemotherapy of S-1 plus oxaliplatin for patients with stage III gastric cancer after D2 gastrectomy. Gastric Cancer, 20:175-181, 2017

36. Hatogai K, Fujii S, Kojima T, Daiko H, Nomura S, Doi T, Kitano S, Ohtsu A, Takiguchi Y, Yoshino T, Ochiai A. Large-scale comprehensive immunohistochemical biomarker analyses in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol, 143:2351-2361, 2017

37. Nishikawa K, Takahashi T, Takaishi H, Miki A, Noshiro H, Yoshikawa T, Nishida Y, Iwasa S, Miwa H, Masuishi T, Boku N, Yamada Y, Kodera Y, Yoshida K, Morita S, Sakamoto J, Saji S, Kitagawa Y. Phase II study of the effectiveness and safety of trastuzumab and paclitaxel for taxane- and trastuzumab-naive patients with HER2-positive, previously treated, advanced, or recurrent gastric cancer (JFMC45-1102). Int J Cancer, 140:188-196, 2017

38. Doi T, Fuse N, Yoshino T, Kojima T, Bando H, Miyamoto H, Kaneko M, Osada M, Ohtsu A. A Phase I study of intravenous PI3K inhibitor copanlisib in Japanese patients with advanced or refractory solid tumors. Cancer Chemother Pharmacol, 79:89-98, 2017

39. Kuboki Y, Nishina T, Shinozaki E, Yamazaki K, Shitara K, Okamoto W, Kajiwara T, Matsumoto T, Tsushima T, Mochizuki N, Nomura S, Doi T, Sato A, Ohtsu A, Yoshino T. TAS-102 plus bevacizumab for patients with metastatic colorectal cancer refractory to standard therapies (C-TASK FORCE): an investigator-initiated, open-label, single-arm, multicentre, phase 1/2 study. Lancet Oncol, 18:1172-1181, 2017

40. Matsui H, Hazama S, Sakamoto K, Shindo Y, Kanekiyo S, Nakashima M, Matsukuma S, Tokuhisa Y, Iida M, Suzuki N, Yoshimura K, Takeda S, Ueno T, Yoshino S, Oka M, Nagano H. Postoperative Adjuvant Therapy for Resectable Pancreatic Cancer With Gemcitabine and Adoptive Immunotherapy. Pancreas, 46:994-1002, 2017

41. Nishimura T, Iwasa S, Nagashima K, Okita N, Takashima A, Honma Y, Kato K, Hamaguchi T, Yamada Y, Shimada Y, Boku N. Irinotecan monotherapy as third-line treatment for advanced gastric cancer refractory to fluoropyrimidines, platinum, and taxanes. Gastric Cancer, 20:655-662, 2017

42. Sasada S, Kurihara H, Kinoshita T, Yoshida M, Honda N, Shimoi T, Shimomura A, Yonemori K, Shimizu C, Hamada A, Kanayama Y, Watanabe Y, Fujiwara Y, Tamura K. Visualization of HER2-specific breast cancer intratumoral heterogeneity using 64Cu-DOTA-trastuzumab PET. Eur J Nucl Med Mol Imaging, 44:2146-2147, 2017

43. Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. The lancet. Gastroenterology & hepatology, 2:277-287, 2017

44. Shimada Y, Kohno T, Ueno H, Ino Y, Hayashi H, Nakaoku T, Sakamoto Y, Kondo S, Morizane C, Shimada K, Okusaka T, Hiraoka N. An Oncogenic ALK Fusion and an RRAS Mutation in KRAS Mutation-Negative Pancreatic Ductal Adenocarcinoma. Oncologist, 22:158-164, 2017

45. Terazawa T, Nishitani H, Kato K, Hashimoto H, Akiyoshi K, Ito Y, Nakamoto A, Iwasa S, Nakajima TE, Hamaguchi T, Yamada Y, Shimada Y. Phase II study of cetuximab with irinotecan for KRAS wild-type colorectal cancer in Japanese patients. Asia Pac J Clin Oncol, 13:e132-e137, 2017

46. Asao T, Fujiwara Y, Itahashi K, Kitahara S, Goto Y, Horinouchi H, Kanda S, Nokihara H, Yamamoto N, Takahashi K, Ohe Y. Sequential Use of Anaplastic Lymphoma Kinase Inhibitors in Japanese Patients With ALK-Rearranged Non-Small-Cell Lung Cancer: A Retrospective Analysis. Clin Lung Cancer, 18:e251-e258, 2017

47. Okuma HS, Horinouchi H, Kitahara S, Asao T, Sunami K, Goto Y, Kanda S, Fujiwara Y, Nokihara H, Yamamoto N, Ohe Y. Comparison of Amrubicin and Weekly Cisplatin/Etoposide/Irinotecan in Patients With Relapsed Small-cell Lung Cancer. Clin Lung Cancer, 18:234-240 e2, 2017

48. Yamamoto N, Nokihara H, Yamada Y, Shibata T, Tamura Y, Seki Y, Honda K, Tanabe Y, Wakui H, Tamura T. Phase I study of Nivolumab, an anti-PD-1 antibody, in patients with malignant solid tumors. Invest New Drugs, 35:207-216, 2017

49. Hisakane K, Yoh K, Nakamura N, Udagawa H, Kirita K, Umemura S, Matsumoto S, Niho S, Akimoto T, Tsuboi M, Goto K. Salvage chemoradiotherapy with cisplatin and vinorelbine for postoperative locoregional recurrence of non-small cell lung cancer. Medicine (Baltimore), 96:e8635, 2017

50. Mukai H, Kogawa T, Matsubara N, Naito Y, Sasaki M, Hosono A. A first-in-human Phase 1 study of epirubicin-conjugated polymer micelles (K-912/NC-6300) in patients with advanced or recurrent solid tumors. Invest New Drugs, 35:307-314, 2017

51. Ishibashi M, Neri S, Hashimoto H, Miyashita T, Yoshida T, Nakamura Y, Udagawa H, Kirita K, Matsumoto S, Umemura S, Yoh K, Niho S, Tsuboi M, Masutomi K, Goto K, Ochiai A, Ishii G. CD200-positive cancer associated fibroblasts augment the sensitivity of Epidermal Growth Factor Receptor mutation-positive lung adenocarcinomas to EGFR Tyrosine kinase inhibitors. Sci Rep, 7:46662, 2017

52. Hatogai K, Fujii S, Kojima T, Daiko H, Doi T, Ohtsu A, Ochiai A, Takiguchi Y, Yoshino T. Concordance between PIK3CA mutations in endoscopic biopsy and surgically resected specimens of esophageal squamous cell carcinoma. BMC Cancer, 17:36, 2017

53. Shitara K. RAINFALL before RAINBOW-an illusion or reality? Translational gastroenterology and hepatology, 2:26, 2017

54. Tanabe Y, Shimizu C, Hamada A, Hashimoto K, Ikeda K, Nishizawa D, Hasegawa J, Shimomura A, Ozaki Y, Tamura N, Yamamoto H, Yunokawa M, Yonemori K, Takano T, Kawabata H, Tamura K, Fujiwara Y. Paclitaxel-induced sensory peripheral neuropathy is associated with an ABCB1 single nucleotide polymorphism and older age in Japanese. Cancer Chemother Pharmacol, 79:1179-1186, 2017

55. Ikeda M, Takahashi H, Kondo S, Lahn MMF, Ogasawara K, Benhadji KA, Fujii H, Ueno H. Phase 1b study of galunisertib in combination with gemcitabine in Japanese patients with metastatic or locally advanced pancreatic cancer. Cancer Chemother Pharmacol, 79:1169-1177, 2017

56. Fujii T, Kogawa T, Wu J, Sahin AA, Liu DD, Chavez-MacGregor M, Giordano SH, Raghavendra A, Murthy RK, Tripathy D, Shen Y, Yamal JM, Ueno NT. Nomogram to predict pathologic complete response in HER2-positive breast cancer treated with neoadjuvant systemic therapy. Br J Cancer, 116:509-514, 2017

57. Usui Y, Udagawa H, Matsumoto S, Imai K, Ohashi K, Ishibashi M, Kirita K, Umemura S, Yoh K, Niho S, Osame K, Goto K. Association of Serum Anti-GAD Antibody and HLA Haplotypes with Type 1 Diabetes Mellitus Triggered by Nivolumab in Patients with Non-Small Cell Lung Cancer. J Thorac Oncol, 12:e41-e43, 2017

58. Shitara K, Doi T, Nagano O, Fukutani M, Hasegawa H, Nomura S, Sato A, Kuwata T, Asai K, Einaga Y, Tsuchihashi K, Suina K, Maeda Y, Saya H, Ohtsu A. Phase 1 study of sulfasalazine and cisplatin for patients with CD44v-positive gastric cancer refractory to cisplatin (EPOC1407). Gastric cancer, 20:1004-1009, 2017

59. Shitara K, Doi T, Nagano O, Imamura CK, Ozeki T, Ishii Y, Tsuchihashi K, Takahashi S, Nakajima TE, Hironaka S, Fukutani M, Hasegawa H, Nomura S, Sato A, Einaga Y, Kuwata T, Saya H, Ohtsu A. Dose-escalation study for the targeting of CD44v+ cancer stem cells by sulfasalazine in patients with advanced gastric cancer (EPOC1205). Gastric Cancer, 20:341-349, 2017

60. Kawazoe A, Kuwata T, Kuboki Y, Shitara K, Nagatsuma AK, Aizawa M, Yoshino T, Doi T, Ohtsu A, Ochiai A. Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein-Barr virus status in a large cohort of gastric cancer patients. Gastric Cancer, 20:407-415, 2017

61. Tanabe Y, Tsuda H, Yoshida M, Yunokawa M, Yonemori K, Shimizu C, Yamamoto S, Kinoshita T, Fujiwara Y, Tamura K. Pathological features of triple-negative breast cancers that showed progressive disease during neoadjuvant chemotherapy. Cancer Sci, 108:1520-1529, 2017

62. Uemura H, Matsubara N, Kinuya S, Hosono M, Yajima Y, Doi T. Safety and efficacy of radium-223 dichloride in Japanese patients with castration-resistant prostate cancer and bone metastases. Int J Clin Oncol, 22:954-963, 2017

63. Kubota K, Yoshioka H, Oshita F, Hida T, Yoh K, Hayashi H, Kato T, Kaneda H, Yamada K, Tanaka H, Ichinose Y, Park K, Cho EK, Lee KH, Lin CB, Yang JC, Hara K, Asato T, Nakagawa K. Phase III, Randomized, Placebo-Controlled, Double-Blind Trial of Motesanib (AMG-706) in Combination With Paclitaxel and Carboplatin in East Asian Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol, 35:3662-3670, 2017

64. Yoh K, Seto T, Satouchi M, Nishio M, Yamamoto N, Murakami H, Nogami N, Matsumoto S, Kohno T, Tsuta K, Tsuchihara K, Ishii G, Nomura S, Sato A, Ohtsu A, Ohe Y, Goto K. Vandetanib in patients with previously treated RET-rearranged advanced non-small-cell lung cancer (LURET): an open-label, multicentre phase 2 trial. Lancet Respir Med, 5:42-50, 2017

65. Kubo E, Yamamoto N, Nokihara H, Fujiwara Y, Horinouchi H, Kanda S, Goto Y, Ohe Y. Randomized phase II study of sequential carboplatin plus paclitaxel and gefitinib in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: Long-term follow-up results. Molecular and clinical oncology, 6:56-62, 2017

66. Yoshida A, Arai Y, Kobayashi E, Yonemori K, Ogura K, Hama N, Mukai W, Motoi T, Kawai A, Shibata T, Hiraoka N. CIC break-apart fluorescence in-situ hybridization misses a subset of CIC-DUX4 sarcomas: a clinicopathological and molecular study. Histopathology, 71:461-469, 2017

67. Shimizu T, Yonesaka K, Hayashi H, Iwasa T, Haratani K, Yamada H, Ohwada S, Kamiyama E, Nakagawa K. Phase 1 study of new formulation of patritumab (U3-1287) Process 2, a fully human anti-HER3 monoclonal antibody in combination with erlotinib in Japanese patients with advanced non-small cell lung cancer. Cancer Chemother Pharmacol, 79:489-495, 2017

68. Sasada S, Kurihara H, Kinoshita T, Yoshida M, Honda N, Shimoi T, Shimomura A, Yunokawa M, Yonemori K, Shimizu C, Hamada A, Kanayama Y, Watanabe Y, Fujiwara Y, Tamura K. 64Cu-DOTA-trastuzumab PET imaging for HER2-specific primary lesions of breast cancer. Ann Oncol, 28:2028-2029, 2017

69. Kataoka K, Kinoshita T, Moehler M, Mauer M, Shitara K, Wagner AD, Schrauwen S, Yoshikawa T, Roviello F, Tokunaga M, Boku N, Ducreux M, Terashima M, Lordick F. Current management of liver metastases from gastric cancer: what is common practice? New challenge of EORTC and JCOG. Gastric cancer, 20:904-912, 2017

70. Sasada S, Ushirozawa N, Kobayashi N, Fujiwara Y, Tamura K, Yamamoto N. Surveillance of protocol deviations in Japanese oncology registration trials: a single institute experience. Invest New Drugs, 35:392-396, 2017

71. Nokihara H, Yamamoto N, Yamada Y, Honda K, Asahina H, Tamura Y, Hozak RR, Gao L, Suzukawa K, Enatsu S, Tamura T. A phase 1 study of ramucirumab in Japanese patients with advanced solid tumors. Jpn J Clin Oncol, 47:298-305, 2017

72. Yunokawa M, Yoshida H, Watanabe R, Noguchi E, Shimomura A, Shimoi T, Yonemori K, Shimizu C, Fujiwara Y, Tamura K. Allred score is a promising predictor of prognosis and medroxyprogesterone acetate efficacy in patients with endometrial cancer. Cancer Chemother Pharmacol, 80:127-134, 2017

73. Saito M, Fujiwara Y, Asao T, Honda T, Shimada Y, Kanai Y, Tsuta K, Kono K, Watanabe S, Ohe Y, Kohno T. The genomic and epigenomic landscape in thymic carcinoma. Carcinogenesis, 38:1084-1091, 2017

74. Shinozaki E, Yoshino T, Yamazaki K, Muro K, Yamaguchi K, Nishina T, Yuki S, Shitara K, Bando H, Mimaki S, Nakai C, Matsushima K, Suzuki Y, Akagi K, Yamanaka T, Nomura S, Fujii S, Esumi H, Sugiyama M, Nishida N, Mizokami M, Koh Y, Abe Y, Ohtsu A, Tsuchihara K. Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal antibody treatment in patients with pretreated metastatic colorectal cancer: the Biomarker Research for anti-EGFR monoclonal Antibodies by Comprehensive Cancer genomics (BREAC) study. Br J Cancer, 117:1450-1458, 2017

75. Fukuoka S, Kojima T, Koga Y, Yamauchi M, Komatsu M, Komatsuzaki R, Sasaki H, Yasunaga M, Matsumura Y, Doi T, Ohtsu A. Preclinical efficacy of Sym004, novel anti-EGFR antibody mixture, in esophageal squamous cell carcinoma cell lines. Oncotarget, 8:11020-11029, 2017

76. Doi T, Yamaguchi K, Komatsu Y, Muro K, Nishina T, Nakajima TE, Tang R, Yang H, Zhang Y, Jung AS, Ang A, Yasui H. A Phase 1/1b tolerability study of rilotumumab alone or in combination with cisplatin and capecitabine in Japanese patients with gastric cancer. Jpn J Clin Oncol, 47:1002-1009, 2017

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