Annual Report 2022

Department of Experimental Therapeutics

Toshihiko Doi, Yasutoshi Kuboki, Kiyotaka Yoh, Yoichi Naito, Kohei Shitara, Kenichi Harano, Junichiro Yuda, Shigehiro Koganemaru, Hiromichi Nakajima

Introduction

 The NCC-EPOC Phase I Group was organized to promote early drug development, especially first in human (FIH) trials, and in 2012 the phase I group consisted of two subunits (NCCE-Kashiwa & NCC-Tsukiji) organized by each hospital. The goal of each of the units is to perform initial clinical evaluation of promising new anti-cancer compounds emerging from the laboratory. Our Phase 1 unit is the largest program in Japan, indeed in Asia, and we contribute to the development of new cancer drugs through early phase trials.

 In April 2013, the Department of Experimental Therapeutics was launched to strongly promote the EPOC missions as previously described. The members of the Department of Experimental Therapeutics consisted of specialists in their oncology fields. We have also conducted/contributed to IIT using unapproved drugs and new academic seeds.

The Team and What We Do

 Our team has conducted and managed early drug development, especially first in human (FIH) trials.

Research Activities

 This department plays an important role in new anti-cancer drug development in our center as well as in Japan, and while conducting FIH trials is the top priority, we also perform phase I trials. Recently, we joined the global phase I trial to accelerate new drug development in Japan. Web or teleconferences are held with the EU and US sites, and we are discussing patient enrollment as well as further developmental strategies. Routine web conferences are also held between the Kashiwa and Tsukiji campuses every Friday morning; we share information about adverse events and patient enrollment as well as referring the candidates to each other to accelerate enrollment. Several IIT-FIH trials using new class seeds and also unapproved company agents are conducted by each unit.

Clinical Trials

 In 2022, 175 patients were enrolled in the phase I trial.

List of papers published in 2022

Journal

1. Udagawa H, Takahashi S, Hirao M, Tahara M, Iwasa S, Sato Y, Hamakawa T, Shitara K, Horinouchi H, Chin K, Masuda N, Suzuki T, Okumura S, Takase T, Nagai R, Yonemori K. Liposomal eribulin for advanced adenoid cystic carcinoma, gastric cancer, esophageal cancer, and small cell lung cancer. Cancer medicine, 12:1269-1278, 2023

2. Goto Y, Yoh K, Kato T, Hosomi Y, Usui K, Fukui T, Hirano K, Tanaka H, Taguri M, Kunitoh H. Observational study to predict the efficacy and optimal duration of nivolumab treatment in patients with previously treated advanced or recurrent non-small cell lung cancer. Japanese journal of clinical oncology, 53:153-160, 2023

3. Doi T, Shitara K, Kojima T, Kuboki Y, Matsubara N, Bando H, Yoh K, Naito Y, Hirai H, Kurokawa Y, Kato T, Morizane C. Phase I study of the irreversible fibroblast growth factor receptor 1-4 inhibitor futibatinib in Japanese patients with advanced solid tumors. Cancer science, 114:574-585, 2023

4. Hosono N, Chi S, Yamauchi T, Fukushima K, Shibayama H, Katagiri S, Gotoh A, Eguchi M, Morishita T, Ogasawara R, Kondo T, Yanada M, Yamamoto K, Kobayashi T, Kuroda J, Usuki K, Utsu Y, Yoshimitsu M, Ishitsuka K, Ono T, Takahashi N, Iyama S, Kojima K, Nakamura Y, Fukuhara S, Izutsu K, Abutani H, Yamauchi N, Yuda J, Minami Y. Clinical utility of genomic profiling of AML using paraffin-embedded bone marrow clots: HM-SCREEN-Japan 01. Cancer science, 114:2098-2108, 2023

5. Shitara K, Hirao M, Iwasa S, Oshima T, Komatsu Y, Kawazoe A, Sato Y, Hamakawa T, Yonemori K, Machida N, Yuki S, Suzuki T, Okumura S, Takase T, Semba T, Zimmermann B, Teng A, Yamaguchi K. Phase I Study of the Liposomal Formulation of Eribulin (E7389-LF): Results from the Advanced Gastric Cancer Expansion Cohort. Clinical cancer research, 29:1460-1467, 2023

6. Funasaka C, Naito Y, Kusuhara S, Nakao T, Nakajima H, Kawamoto M, Baba K, Mamishin K, Kondoh C, Harano K, Matsubara N, Hosono A, Sasaki T, Kawasaki T, Mukohara T. Clinical features of CDK4/6 inhibitor-related interstitial lung disease in patients with breast cancer: a case series study. Japanese journal of clinical oncology, 53:105-114, 2023

7. Koganemaru S, Kawai T, Fuchigami H, Maeda N, Koyama K, Kuboki Y, Mukohara T, Doi T, Yasunaga M. Quantitative analysis of drug distribution in heterogeneous tissues using dual-stacking capillary electrophoresis-mass spectrometry. British journal of pharmacology, 180:762-774, 2023

8. Naito Y, Nishida T, Doi T. Current status of and future prospects for the treatment of unresectable or metastatic gastrointestinal stromal tumours. Gastric cancer, 26:339-351, 2023

9. Sugimoto A, Matsumoto S, Udagawa H, Itotani R, Usui Y, Umemura S, Nishino K, Nakachi I, Kuyama S, Daga H, Hara S, Miyamoto S, Kato T, Sakakibara-Konishi J, Tabata E, Nakagawa T, Kawaguchi T, Sakai T, Shibata Y, Izumi H, Nosaki K, Zenke Y, Yoh K, Goto K. A Large-Scale Prospective Concordance Study of Plasma- and Tissue-Based Next-Generation Targeted Sequencing for Advanced Non-Small Cell Lung Cancer (LC-SCRUM-Liquid). Clinical cancer research, 29:1506-1514, 2023

10. Tamiya Y, Matsumoto S, Zenke Y, Yoh K, Ikeda T, Shibata Y, Kato T, Nishino K, Nakamura A, Furuya N, Miyamoto S, Kuyama S, Nomura S, Ikeno T, Udagawa H, Sugiyama E, Nosaki K, Izumi H, Sakai T, Hashimoto N, Goto K. Large-scale clinico-genomic profile of non-small cell lung cancer with KRAS G12C: Results from LC-SCRUM-Asia study. Lung cancer (Amsterdam, Netherlands), 176:103-111, 2023

11. Tanaka Y, Nakai T, Suzuki A, Kagawa Y, Noritake O, Taki T, Hashimoto H, Sakai T, Shibata Y, Izumi H, Nosaki K, Udagawa H, Zenke Y, Matsumoto S, Yoh K, Miyazaki S, Sakamoto N, Sakashita S, Kojima M, Watanbe R, Tsuboi M, Goto K, Ishii G. Clinicopathological significance of peritumoral alveolar macrophages in patients with resected early-stage lung squamous cell carcinoma. Cancer immunology, immunotherapy, 72:2205-2215, 2023

12. Liu T, Bai Y, Lin X, Li W, Wang J, Zhang X, Pan H, Bai C, Bai L, Cheng Y, Zhang J, Zhong H, Ba Y, Hu W, Xu R, Guo W, Qin S, Yang N, Lu J, Shitara K, Lei M, Li M, Bao N, Chen T, Shen L. First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric, gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis. International journal of cancer, 152:749-760, 2023

13. Yamaguchi K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Shimoyama T, Lee KW, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Shitara K. Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial. Journal of clinical oncology, 41:816-825, 2023

14. Shitara K, Kawazoe A, Hirakawa A, Nakanishi Y, Furuki S, Fukuda M, Ueno Y, Raizer J, Arozullah A. Phase 1 trial of zolbetuximab in Japanese patients with CLDN18.2+ gastric or gastroesophageal junction adenocarcinoma. Cancer science, 114:1606-1615, 2023

15. Yoshino T, Taieb J, Kuboki Y, Pfeiffer P, Kumar A, Hochster HS. Trifluridine/tipiracil with or without bevacizumab in metastatic colorectal cancer: results of a systematic review and meta-analysis. Therapeutic advances in medical oncology, 15:17588359221146137, 2023

16. Yuda J, Doki N, Matsuoka H, Yokota T, Tomita A, Takahashi N, Matsumura I, Kubo K, Goto T, Kirito K, Maki A, Aoki M, Allepuz A, Minami Y. Asciminib vs bosutinib in CML patients pretreated with ≧2 tyrosine kinase inhibitors: Results from the Japanese subgroup analysis of ASCEMBL study. Cancer medicine, 12:2990-2998, 2023

17. Tahir SK, Calvo E, Carneiro BA, Yuda J, Shreenivas A, Jongen-Lavrencic M, Gort E, Ishizawa K, Morillo D, Biesdorf C, Smith M, Cheng D, Motwani M, Sharon D, Uziel T, Modi DA, Buchanan FG, Morgan-Lappe S, Medeiros BC, Phillips DC. Activity of eftozanermin alfa plus venetoclax in preclinical models and patients with acute myeloid leukemia. Blood, 2023

18. Kubota Y, Kawazoe A, Mishima S, Nakamura Y, Kotani D, Kuboki Y, Bando H, Kojima T, Doi T, Yoshino T, Kuwata T, Shitara K. Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer. ESMO open, 8:100762, 2023

19. Kuboki Y, Terazawa T, Masuishi T, Nakamura M, Watanabe J, Ojima H, Makiyama A, Kotaka M, Hara H, Kagawa Y, Sugimoto N, Kawakami H, Takashima A, Kajiwara T, Oki E, Sunakawa Y, Ishihara S, Taniguchi H, Nakajima TE, Morita S, Shirao K, Takenaka N, Ozawa D, Yoshino T. Trifluridine/tipiracil+bevacizumab (BEV) vs. fluoropyrimidine-irinotecan+BEV as second-line therapy for metastatic colorectal cancer: a randomised noninferiority trial. British journal of cancer, 128:1897-1905, 2023

20. Fujiwara Y, Kuboki Y, Furukawa M, Mizuno N, Hara H, Ioka T, Ueno M, Takahashi Y, Takahashi S, Takeuchi S, Lihou C, Ji T, Tian C, Shimizu T. FIGHT-102: A phase 1 study of pemigatinib in Japanese patients with advanced malignancies. Cancer medicine, 12:10597-10611, 2023

21. Hasegawa H, Shitara K, Takiguchi S, Takiguchi N, Ito S, Kochi M, Horinouchi H, Kinoshita T, Yoshikawa T, Muro K, Nishikawa H, Suna H, Kodera Y. A multicenter, open-label, single-arm phase I trial of neoadjuvant nivolumab monotherapy for resectable gastric cancer. Gastric cancer, 25:619-628, 2022

22. Ohe Y, Yamazaki N, Yamamoto N, Murakami H, Yoh K, Kitano S, Hashimoto H, Murayama A, Nakane S, Gemma A. The real-world safety of atezolizumab as second-line or later treatment in Japanese patients with non-small-cell lung cancer: a post-marketing surveillance study. Japanese journal of clinical oncology, 52:623-632, 2022

23. Shukuya T, Takamochi K, Sakurai H, Yoh K, Hishida T, Tsuboi M, Goto Y, Kudo Y, Ohde Y, Okumura S, Taguri M, Kunitoh H. Efficacy of Adjuvant Chemotherapy With Tegafur-Uracil in Patients With Completely Resected, Node-Negative NSCLC-Real-World Data in the Era of Molecularly Targeted Agents and Immunotherapy. JTO clinical and research reports, 3:100320, 2022

24. Itahashi K, Irie T, Yuda J, Kumagai S, Tanegashima T, Lin YT, Watanabe S, Goto Y, Suzuki J, Aokage K, Tsuboi M, Minami Y, Ishii G, Ohe Y, Ise W, Kurosaki T, Suzuki Y, Koyama S, Nishikawa H. BATF epigenetically and transcriptionally controls the activation program of regulatory T cells in human tumors. Science immunology, 7:eabk0957, 2022

25. Kojima T, Hara H, Tsuji A, Yasui H, Muro K, Satoh T, Ogata T, Ishihara R, Goto M, Baba H, Nishina T, Han S, Sakata T, Yatsuzuka N, Doi T, Kato K. First-line pembrolizumab + chemotherapy in Japanese patients with advanced/metastatic esophageal cancer from KEYNOTE-590. Esophagus, 19:683-692, 2022

26. Kurokawa Y, Honma Y, Sawaki A, Naito Y, Iwagami S, Komatsu Y, Takahashi T, Nishida T, Doi T. Pimitespib in patients with advanced gastrointestinal stromal tumor (CHAPTER-GIST-301): a randomized, double-blind, placebo-controlled phase III trial. Annals of oncology, 33:959-967, 2022

27. Yamaguchi K, Minashi K, Sakai D, Nishina T, Omuro Y, Tsuda M, Iwagami S, Kawakami H, Esaki T, Sugimoto N, Oshima T, Kato K, Amagai K, Hosaka H, Komine K, Yasui H, Negoro Y, Ishido K, Tsushima T, Han S, Shiratori S, Takami T, Shitara K. Phase IIb study of pembrolizumab combined with S-1 + oxaliplatin or S-1 + cisplatin as first-line chemotherapy for gastric cancer. Cancer science, 113:2814-2827, 2022

28. Kojima T, Kato K, Hara H, Takahashi S, Muro K, Nishina T, Wakabayashi M, Nomura S, Sato A, Ohtsu A, Doi T. Phase II study of BKM120 in patients with advanced esophageal squamous cell carcinoma (EPOC1303). Esophagus, 19:702-710, 2022

29. Fukuhara S, Oshikawa-Kumade Y, Kogure Y, Shingaki S, Kariyazono H, Kikukawa Y, Koya J, Saito Y, Tabata M, Yoshifuji K, Mizuno K, Miyagi-Maeshima A, Matsushita H, Sugiyama M, Ogawa C, Inamoto Y, Fukuda T, Sugano M, Yamauchi N, Minami Y, Hirata M, Yoshida T, Kohno T, Kohsaka S, Mano H, Shiraishi Y, Ogawa S, Izutsu K, Kataoka K. Feasibility and clinical utility of comprehensive genomic profiling of hematological malignancies. Cancer science, 113:2763-2777, 2022

30. Yonemori K, Kuboki Y, Hasegawa K, Iwata T, Kato H, Takehara K, Hirashima Y, Kato H, Passey C, Buchbjerg JK, Harris JR, Andreassen CM, Nicacio L, Soumaoro I, Fujiwara K. Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study. Cancer science, 113:2788-2797, 2022

31. Imai M, Nakamura Y, Sunami K, Kage H, Komine K, Koyama T, Amano T, Ennishi D, Kanai M, Kenmotsu H, Maeda T, Morita S, Sakai D, Bando H, Makiyama A, Suzuki T, Hirata M, Kohsaka S, Tsuchihara K, Naito Y, Yoshino T. Expert panel consensus recommendations on the use of circulating tumor DNA assays for patients with advanced solid tumors. Cancer science, 113:3646-3656, 2022

32. Sunami K, Naito Y, Komine K, Amano T, Ennishi D, Imai M, Kage H, Kanai M, Kenmotsu H, Koyama T, Maeda T, Morita S, Sakai D, Kohsaka S, Tsuchihara K, Saigusa Y, Yoshino T. Chronological improvement in precision oncology implementation in Japan. Cancer science, 113:3995-4000, 2022

33. Naito Y, Sunami K, Kage H, Komine K, Amano T, Imai M, Koyama T, Ennishi D, Kanai M, Kenmotsu H, Maeda T, Morita S, Sakai D, Watanabe K, Shirota H, Kinoshita I, Yoshioka M, Mamesaya N, Ito M, Kohsaka S, Saigusa Y, Yamamoto K, Hirata M, Tsuchihara K, Yoshino T. Concordance Between Recommendations From Multidisciplinary Molecular Tumor Boards and Central Consensus for Cancer Treatment in Japan. JAMA network open, 5:e2245081, 2022

34. Nishio S, Yonemori K, Usami T, Minobe S, Yunokawa M, Iwata T, Okamoto A, Aoki Y, Itamochi H, Takekuma M, Harano K, Yamamoto K, Maruko T, Ugai H, Tekin C, Colombo N, Fujiwara K, Hasegawa K, Ushijima K. Pembrolizumab plus chemotherapy in Japanese patients with persistent, recurrent or metastatic cervical cancer: Results from KEYNOTE-826. Cancer science, 113:3877-3887, 2022

35. Masuda N, Ono M, Mukohara T, Yasojima H, Shimoi T, Kobayashi K, Harano K, Mizutani M, Tanioka M, Takahashi S, Kogawa T, Suzuki T, Okumura S, Takase T, Nagai R, Semba T, Zhao ZM, Ren M, Yonemori K. Phase 1 study of the liposomal formulation of eribulin (E7389-LF): Results from the breast cancer expansion cohort. European journal of cancer (Oxford, England : 1990), 168:108-118, 2022

36. Kotani H, Masuda N, Yamashita T, Naito Y, Taira T, Inoue K, Takahashi M, Yonemori K, Toyoizumi S, Mori Y, Nagasawa T, Hori N, Iwata H. Efficacy and safety of talazoparib in Japanese patients with germline BRCA-mutated locally advanced or metastatic breast cancer: results of the phase 1 dose-expansion study. Breast cancer (Tokyo, Japan), 29:1088-1098, 2022

37. Yasui H, Takeno A, Hara H, Imamura H, Akamatsu H, Fujitani K, Nakane M, Kondoh CN, Yukisawa S, Nasu J, Miyata Y, Makiyama A, Ishida H, Yoshida N, Matsumura E, Ishigami M, Sugihara M, Ochiai A, Doi T. Prospective analysis of the expression status of FGFR2 and HER2 in colorectal and gastric cancer populations: DS-Screen Study. International journal of colorectal disease, 37:1393-1402, 2022

38. Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. The New England journal of medicine, 387:9-20, 2022

39. Niguma K, Mamishin K, Naito Y, Nomura S, Wakabayashi M, Kusuhara S, Funasaka C, Nakao T, Fukasawa Y, Kondoh C, Harano K, Kogawa T, Matsubara N, Hosono A, Onishi T, Kawasaki T, Mukohara T. Impact of Older Age and Medico-social Factors on the Decision to Offer Adjuvant Chemotherapy to Patients With Breast Cancer. Anticancer research, 42:3743-3751, 2022

40. Abe Y, Taira N, Kashiwabara K, Tsurutani J, Kitada M, Takahashi M, Kato H, Kikawa Y, Sakata E, Naito Y, Hasegawa Y, Saito T, Iwasa T, Takashima T, Aihara T, Mukai H, Hara F, Shien T, Doihara H, Toyooka S. Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients. Acta medica Okayama, 76:661-671, 2022

41. Kuboki Y, Shimizu T, Yonemori K, Kojima T, Kondo S, Koganemaru S, Iwasa S, Harano K, Koyama T, Lu V, Zhou X, Niu H, Yanai T, Garcia-Ribas I, Doi T, Yamamoto N. Safety, Tolerability, and Pharmacokinetics of TAK-931, a Cell Division Cycle 7 Inhibitor, in Patients with Advanced Solid Tumors: A Phase I First-in-Human Study. Cancer research communications, 2:1426-1435, 2022

42. Remon J, Lacas B, Herbst R, Reck M, Garon EB, Scagliotti GV, Ramlau R, Hanna N, Vansteenkiste J, Yoh K, Groen HJM, Heymach JV, Mandrekar SJ, Okamoto I, Neal JW, Heist RS, Planchard D, Pignon JP, Besse B. ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer: ANSELMA. European journal of cancer (Oxford, England : 1990), 166:112-125, 2022

43. Tamiya Y, Nakai T, Suzuki A, Mimaki S, Tsuchihara K, Sato K, Yoh K, Matsumoto S, Zenke Y, Nosaki K, Izumi H, Shibata Y, Sakai T, Taki T, Miyazaki S, Watanabe R, Sakamoto N, Sakashita S, Kojima M, Hashimoto N, Tsuboi M, Goto K, Ishii G. The impact of tertiary lymphoid structures on clinicopathological, genetic and gene expression characteristics in lung adenocarcinoma. Lung cancer (Amsterdam, Netherlands), 174:125-132, 2022

44. Shitara K, Doi T, Hosaka H, Thuss-Patience P, Santoro A, Longo F, Ozyilkan O, Cicin I, Park D, Zaanan A, Pericay C, Özgüroğlu M, Alsina M, Makris L, Benhadji KA, Ilson DH. Efficacy and safety of trifluridine/tipiracil in older and younger patients with metastatic gastric or gastroesophageal junction cancer: subgroup analysis of a randomized phase 3 study (TAGS). Gastric cancer, 25:586-597, 2022

45. Chida K, Kawazoe A, Suzuki T, Kawazu M, Ueno T, Takenouchi K, Nakamura Y, Kuboki Y, Kotani D, Kojima T, Bando H, Mishima S, Kuwata T, Sakamoto N, Watanabe J, Mano H, Ikeda M, Shitara K, Endo I, Nakatsura T, Yoshino T. Transcriptomic Profiling of MSI-H/dMMR Gastrointestinal Tumors to Identify Determinants of Responsiveness to Anti-PD-1 Therapy. Clinical cancer research, 28:2110-2117, 2022

46. Maron SB, Moya S, Morano F, Emmett MJ, Chou JF, Sabwa S, Walch H, Peterson B, Schrock AB, Zhang L, Janjigian YY, Chalasani S, Ku GY, Disel U, Enzinger P, Uboha N, Kato S, Yoshino T, Shitara K, Nakamura Y, Saeed A, Kasi PM, Chao J, Lee J, Capanu M, Wainberg Z, Petty R, Pietrantonio F, Klempner SJ, Catenacci DVT. Epidermal Growth Factor Receptor Inhibition in Epidermal Growth Factor Receptor-Amplified Gastroesophageal Cancer: Retrospective Global Experience. Journal of clinical oncology, 40:2458-2467, 2022

47. Swain SM, Nishino M, Lancaster LH, Li BT, Nicholson AG, Bartholmai BJ, Naidoo J, Schumacher-Wulf E, Shitara K, Tsurutani J, Conte P, Kato T, Andre F, Powell CA. Multidisciplinary clinical guidance on trastuzumab deruxtecan (T-DXd)-related interstitial lung disease/pneumonitis-Focus on proactive monitoring, diagnosis, and management. Cancer treatment reviews, 106:102378, 2022

48. Myer NM, Shitara K, Chung HC, Lordick F, Kelly RJ, Szabo Z, Cao ZA, Leong S, Ilson DH, Weichert W. Evolution of predictive and prognostic biomarkers in the treatment of advanced gastric cancer. Journal of cancer research and clinical oncology, 148:2023-2043, 2022

49. Shah MA, Shitara K, Lordick F, Bang YJ, Tebbutt NC, Metges JP, Muro K, Lee KW, Shen L, Tjulandin S, Hays JL, Starling N, Xu RH, Sturtz K, Fontaine M, Oh C, Brooks E, Xu B, Li W, Li CJ, Borodyansky L, Van Cutsem E. Randomized, double-blind, placebo-controlled phase 3 study of paclitaxel {plus minus} napabucasin in pretreated advanced gastric or gastroesophageal junction adenocarcinoma. Clinical cancer research, 28:3686-3694, 2022

50. Lee KW, Van Cutsem E, Bang YJ, Fuchs CS, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Chao J, Wainberg ZA, Cao ZA, Aurora-Garg D, Kobie J, Cristescu R, Bhagia P, Shah S, Tabernero J, Shitara K, Wyrwicz L. Association of Tumor Mutational Burden with Efficacy of Pembrolizumab±Chemotherapy as First-Line Therapy for Gastric Cancer in the Phase III KEYNOTE-062 Study. Clinical cancer research, 28:3489-3498, 2022

51. Yukami H, Kawazoe A, Lin YT, Koyama S, Fukuoka S, Hara H, Takahashi N, Kojima T, Asayama M, Yoshii T, Bando H, Kotani D, Nakamura Y, Kuboki Y, Mishima S, Wakabayashi M, Kuwata T, Goto M, Higuchi K, Yoshino T, Doi T, Nishikawa H, Shitara K. Updated Efficacy Outcomes of Anti-PD-1 Antibodies plus Multikinase Inhibitors for Patients with Advanced Gastric Cancer with or without Liver Metastases in Clinical Trials. Clinical cancer research, 28:3480-3488, 2022

52. Aoki Y, Kawazoe A, Kubota Y, Chida K, Mishima S, Kotani D, Nakamura Y, Kuboki Y, Bando H, Kojima T, Doi T, Yoshino T, Kuwata T, Shitara K. Characteristics and clinical outcomes of patients with advanced gastric or gastroesophageal cancer treated in and out of randomized clinical trials of first-line immune checkpoint inhibitors. International journal of clinical oncology, 27:1413-1420, 2022

53. Shah MA, Shitara K, Lordick F, Bang YJ, Tebbutt NC, Metges JP, Muro K, Lee KW, Shen L, Tjulandin S, Hays JL, Starling N, Xu RH, Sturtz K, Fontaine M, Oh C, Brooks EM, Xu B, Li W, Li CJ, Borodyansky L, Van Cutsem E. Randomized, Double-Blind, Placebo-Controlled Phase III Study of Paclitaxel ± Napabucasin in Pretreated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. Clinical cancer research, OF1-OF9, 2022

54. Tabernero J, Shen L, Elimova E, Ku G, Liu T, Shitara K, Lin X, Boyken L, Li H, Grim J, Ajani J. HERIZON-GEA-01: Zanidatamab + chemo ± tislelizumab for 1L treatment of HER2-positive gastroesophageal adenocarcinoma. Future oncology (London, England), 18:3255-3266, 2022

55. Yoon HH, Jin Z, Kour O, Kankeu Fonkoua LA, Shitara K, Gibson MK, Prokop LJ, Moehler M, Kang YK, Shi Q, Ajani JA. Association of PD-L1 Expression and Other Variables With Benefit From Immune Checkpoint Inhibition in Advanced Gastroesophageal Cancer: Systematic Review and Meta-analysis of 17 Phase 3 Randomized Clinical Trials. JAMA oncology, 8:1456-1465, 2022

56. Kubota Y, Aoki Y, Kawazoe A, Shitara K. Role of Nivolumab in the Management of First-Line Unresectable Advanced or Recurrent Gastric Cancer in Combination with Chemotherapy: Lessons from the Japanese Experience. Cancer management and research, 14:3083-3094, 2022

57. El Helali A, Tao J, Wong CHL, Chan WW, Mok KC, Wu WF, Shitara K, Mohler M, Boku N, Pang H, Lam KO. A meta-analysis with systematic review: Efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer. Frontiers in oncology, 12:908026, 2022

58. Morinaga T, Inozume T, Kawazu M, Ueda Y, Sax N, Yamashita K, Kawashima S, Nagasaki J, Ueno T, Lin J, Ohara Y, Kuwata T, Yukami H, Kawazoe A, Shitara K, Honobe-Tabuchi A, Ohnuma T, Kawamura T, Umeda Y, Kawahara Y, Nakamura Y, Kiniwa Y, Morita A, Ichihara E, Kiura K, Enokida T, Tahara M, Hasegawa Y, Mano H, Suzuki Y, Nishikawa H, Togashi Y. Mixed Response to Cancer Immunotherapy is Driven by Intratumor Heterogeneity and Differential Interlesion Immune Infiltration. Cancer research communications, 2:739-753, 2022

59. Katagiri S, Chi S, Minami Y, Fukushima K, Shibayama H, Hosono N, Yamauchi T, Morishita T, Kondo T, Yanada M, Yamamoto K, Kuroda J, Usuki K, Akahane D, Gotoh A. Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia. International journal of molecular sciences, 23:4694, 2022

60. Ikeda D, Chi S, Uchiyama S, Nakamura H, Guo YM, Yamauchi N, Yuda J, Minami Y. Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors. International journal of molecular sciences, 23:5950, 2022

61. Shimizu T, Kuboki Y, Lin CC, Yonemori K, Yanai T, Faller DV, Dobler L, Gupta N, Sedarati F, Kim KP. A Phase 1 Study of Sapanisertib (TAK-228) in East Asian Patients with Advanced Nonhematological Malignancies. Targeted oncology, 17:15-24, 2022

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