Annual Report 2019
Department of Gastrointestinal Oncology
Takayuki Yoshino, Toshihiko Doi, Takashi Kojima, Kouhei Shitara, Nozomu Fuse, Hiroya Taniguchi, Yasutoshi Kuboki, Akihito Kawazoe, Daisuke Kotani, Yoshiaki Nakamura, Masataka Yagisawa, Keigo Chida, Saori Mishima
Introduction
In 2018, approximately 770 gastrointestinal (GI) cancer patients were treated by staff oncologists and skilled residents in the Department of GI Oncology, which focuses on the optimal chemotherapy W/ or W/O radiation for the treatment of GI cancers.
The Team and What We Do
Inter-divisional tumor board conferences with the Surgical/Radiation Oncology Divisions are held regularly to review the current treatment for each patient and to discuss the further treatment strategies. Our activities for each type of GI cancer in 2019 are shown in Table 1. There are ongoing clinical trials which consist of 73 phase I trials including globally first-in-class (FIC), first-in-human (FIH), and investigational new drugs (INDs), 46 phase II/III clinical trials in order to approve the INDs, and 20 investigator-initiated clinical trials (IITs). In addition, young skilled residents in their early 30s have become principal investigators for several IITs.
Table1. Number of surgical cases from Apr. 2019 to Mar. 2020
Activities
Phase I
Our Department has focused more on early stage clinical development of INDs. The number for patients enrolled for phase 1 trials have been increasing recently, especially for studies for immunomodulating agents. Furthermore, new types of cancer therapy such as antibody drug conjugate (ADC) or cell therapies using chimeric antigen receptor (CAR)-T cells, and bispecific T-cell engager antibody (BiTE)-a complex formed with antibodies against CD3 and antibodies against tumor cell surface antigens-will be more focused on solid tumors including GI tumors.
Esophageal Cancer (EC)
Enrollment for a phase I trial of an oncolytic virus and pembrolizumab and a phase Ib/II study to investigate the safety, efficacy, and proof-of-concept (POC) of Anti PD-L1 antibody monotherapy following radical chemoradiotherapy are ongoing. In addition, an observational study of circulating-tumor DNA in patients with gastrointestinal cancer will be started soon.
Gastric Cancer (GC)
We reported several research projects to clarify the immune profiles in gastric cancer or investigate biomarkers to predict treatment outcomes after PD-1 blockade as collaborations with the division of cancer immunology. The results of a phase 1 trial of nivolumab plus regorafenib, a phase 2 trial of TAS114+S1 for gastric cancer and phase 2 trials of lenvatinib plus pembrolizumab were published in the major journals. The results of phase 1 of TAS-116 and nivolumab was reported and the manuscript is in pre-submission. The enrollment for a phase 1 study of disulfiram as an anti-macrophage treatment in combination with nivolumab for gastric cancer and a phase 1 trial of photoimmunotherapy plus nivolumab are ongoing. Furthermore, a phase 2 trial of neoadjuvant treatment with lenvatinib plus pembrolizumab will be started soon. Our department contributed to several international global studies such as a phase 3 trial of pembrolizumab for gastric cancer and a phase 2 trial of trastuzumab deruxtecan for gastric cancer and published the results in the major journals as the lead author.
Colorectal Cancer (CRC)
We have been conducting our initiative SCRUM-Japan platform, which is a nationwide cancer genome screening system using tumor-tissue (GI-SCREEN and MONSTAR-SCREEN), and circulating tumor-DNA based NGS screening (GOZILA project) for metastatic solid tumors. Utilizing these screening systems, the umbrella type of IITs for metastatic CRC or solid tumor patients with HER2 amplification, BRAF non-V600E mutation, MET amplification, or FGFR alterations are ongoing. We have also started IITs in resectable colorectal cancer (CIRCULATE-Japan project) to stratify them according to recurrence risk based on Signatera assay for detecting minimal residual disease.
Education
Our residents learn the latest evidence-based medicine and apply this knowledge pragmatically to enhance care for patients with GI cancers, and eventually have qualifications as comprehensive GI oncologists through daily practice and direct training from our staff. Accordingly, our staff actively provide numerous valuable opportunities to polish their chemotherapies skills, especially in collaboration with the Department of Experimental Therapeutics as well as diagnostic & therapeutic endoscopies in collaboration with the Department of Digestive Endoscopy. We regularly held tumor board meetings and frequently hold face-to-face meetings with experts in different fields. We instruct them on how to conduct valuable clinical trials, help them attend international academic conferences, and explain the best way to present at academic meetings and work on many high-impact articles in scholarly journals. To date, our department has helped many residents to become ‘true’ skilled GI oncologists who play major roles at leading cancer centers across the country.
Future prospects
We continue to provide the best treatment for cancer patients, the best education for residents, and aim to perform the following activities:
1) To provide more the latest, cutting-edged medicine to cancer patients and to foster the next generation of skilled GI oncologists.
2) To achieve medical innovation in Japan, we aim to play a leading role in the clinical development of INDs by contributing to various types of clinical trials including FIC, FIH early trials, IITs with proof-of-concept, and international clinical trials.
3) To enhance our research activity, we will global research networks with cutting-edged researchers.
List of papers published in 2019
Journal
1. Hashiguchi Y, Muro K, Saito Y, Ito Y, Ajioka Y, Hamaguchi T, Hasegawa K, Hotta K, Ishida H, Ishiguro M, Ishihara S, Kanemitsu Y, Kinugasa Y, Murofushi K, Nakajima TE, Oka S, Tanaka T, Taniguchi H, Tsuji A, Uehara K, Ueno H, Yamanaka T, Yamazaki K, Yoshida M, Yoshino T, Itabashi M, Sakamaki K, Sano K, Shimada Y, Tanaka S, Uetake H, Yamaguchi S, Yamaguchi N, Kobayashi H, Matsuda K, Kotake K, Sugihara K. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol, 25:1-42, 2020
2. Moritani K, Kanemitsu Y, Shida D, Shitara K, Mizusawa J, Katayama H, Hamaguchi T, Shimada Y. A randomized controlled trial comparing primary tumour resection plus chemotherapy with chemotherapy alone in incurable stage IV colorectal cancer: JCOG1007 (iPACS study). Jpn J Clin Oncol, 50:89-93, 2020
3. Hatogai K, Fujii S, Kitano S, Kojima T, Daiko H, Yoshino T, Ohtsu A, Takiguchi Y, Doi T, Ochiai A. Relationship between the immune microenvironment of different locations in a primary tumour and clinical outcomes of oesophageal squamous cell carcinoma. Br J Cancer, 122:413-420, 2020
4. Yoshino T, Cleary JM, Van Cutsem E, Mayer RJ, Ohtsu A, Shinozaki E, Falcone A, Yamazaki K, Nishina T, Garcia-Carbonero R, Komatsu Y, Baba H, Argilés G, Tsuji A, Sobrero A, Yamaguchi K, Peeters M, Muro K, Zaniboni A, Sugimoto N, Shimada Y, Tsuji Y, Hochster HS, Moriwaki T, Tran B, Esaki T, Hamada C, Tanase T, Benedetti F, Makris L, Yamashita F, Lenz HJ. Neutropenia and survival outcomes in metastatic colorectal cancer patients treated with trifluridine/tipiracil in the RECOURSE and J003 trials. Ann Oncol, 31:88-95, 2020
5. Kawazoe A, Shitara K. Trifluridine/tipiracil for the treatment of metastatic gastric cancer. Expert Rev Gastroenterol Hepatol, 14:65-70, 2020
6. Mishima S, Taniguchi H, Akagi K, Baba E, Fujiwara Y, Hirasawa A, Ikeda M, Maeda O, Muro K, Nishihara H, Nishiyama H, Takano T, Tsuchihara K, Yatabe Y, Kodera Y, Yoshino T. Japan Society of Clinical Oncology provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors, cooperated by Japanese Society of Medical Oncology, First Edition. Int J Clin Oncol, 25:217-239, 2020
7. Shitara K, Hara H, Yoshikawa T, Fujitani K, Nishina T, Hosokawa A, Asakawa T, Kawakami S, Muro K. Pertuzumab plus trastuzumab and chemotherapy for Japanese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subgroup analysis of the JACOB trial. Int J Clin Oncol, 25:301-311, 2020
8. Shitara K, Honma Y, Omuro Y, Yamaguchi K, Chin K, Muro K, Nakagawa S, Kawakami S, Hironaka S, Nishina T. Efficacy of trastuzumab emtansine in Japanese patients with previously treated HER2-positive locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma: A subgroup analysis of the GATSBY study. Asia Pac J Clin Oncol, 16:5-13, 2020
9. Kotani D, Bando H, Taniguchi H, Masuishi T, Komatsu Y, Yamaguchi K, Nakajima T, Satoh T, Nishina T, Esaki T. BIG BANG study (EPOC1703): multicentre, proof-of-concept, phase II study evaluating the efficacy and safety of combination therapy with binimetinib, encorafenib and cetuximab in patients with BRAF non-V600E mutated metastatic colorectal cancer. ESMO open, 5:e000624, 2020
10. Fujii S, Magliocco AM, Kim J, Okamoto W, Kim JE, Sawada K, Nakamura Y, Kopetz S, Park WY, Tsuchihara K, Kim TW, Raghav K, Yoshino T. International Harmonization of Provisional Diagnostic Criteria for ERBB2-Amplified Metastatic Colorectal Cancer Allowing for Screening by Next-Generation Sequencing Panel. JCO Precision Oncology, 4:6-19, 2020
11. Yamazaki K, Matsumoto S, Imamura CK, Yamagiwa C, Shimizu A, Yoshino T. Clinical impact of baseline renal function on safety and early discontinuation of adjuvant capecitabine plus oxaliplatin in elderly patients with resected colon cancer: a multicenter post-marketing surveillance study. Jpn J Clin Oncol, 50:122-128, 2020
12. Park K, Vansteenkiste J, Lee KH, Pentheroudakis G, Zhou C, Prabhash K, Seto T, Voon PJ, Tan DSW, Yang JCH, Wang J, Babu KG, Nakayama Y, Alip A, Chua KLM, Cheng JC, Senan S, Ahn YC, Kim TY, Ahn HK, Peters S, Yoshino T, Douillard JY. Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with locally-advanced unresectable non-small-cell lung cancer: a KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS. Ann Oncol, 31:191-201, 2020
13. Naito Y, Mishima S, Akagi K, Igarashi A, Ikeda M, Okano S, Kato S, Takano T, Tsuchihara K, Terashima K, Nishihara H, Nishiyama H, Hiyama E, Hirasawa A, Hosoi H, Maeda O, Yatabe Y, Okamoto W, Ono S, Kajiyama H, Nagashima F, Hatanaka Y, Miyachi M, Kodera Y, Yoshino T, Taniguchi H. Japan society of clinical oncology/Japanese society of medical oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese society of pediatric hematology/oncology. Int J Clin Oncol, 25:403-417, 2020
14. Le DT, Kim TW, Van Cutsem E, Geva R, Jäger D, Hara H, Burge M, O'Neil B, Kavan P, Yoshino T, Guimbaud R, Taniguchi H, Elez E, Al-Batran SE, Boland PM, Crocenzi T, Atreya CE, Cui Y, Dai T, Marinello P, Diaz LA Jr, André T. Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: KEYNOTE-164. J Clin Oncol, 38:11-19, 2020
15. Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, Geva R, Gottfried M, Penel N, Hansen AR, Piha-Paul SA, Doi T, Gao B, Chung HC, Lopez-Martin J, Bang YJ, Frommer RS, Shah M, Ghori R, Joe AK, Pruitt SK, Diaz LA Jr. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol, 38:1-10, 2020
16. Moro H, Hattori N, Nakamura Y, Kimura K, Imai T, Maeda M, Yashiro M, Ushijima T. Epigenetic priming sensitizes gastric cancer cells to irinotecan and cisplatin by restoring multiple pathways. Gastric Cancer, 23:105-115, 2020
17. Demachi K, Bando H, Nomura H, Shitara K, Yoshino T, Yamaguchi M, Kawasaki T. Clinical impact of renal impairment on the safety and efficacy of S-1 plus oxaliplatin in patients with advanced gastric cancer: a single institutional study. Jpn J Clin Oncol, 50:129-137, 2020
18. Chen LT, Martinelli E, Cheng AL, Pentheroudakis G, Qin S, Bhattacharyya GS, Ikeda M, Lim HY, Ho GF, Choo SP, Ren Z, Malhotra H, Ueno M, Ryoo BY, Kiang TC, Tai D, Vogel A, Cervantes A, Lu SN, Yen CJ, Huang YH, Chen SC, Hsu C, Shen YC, Tabernero J, Yen Y, Hsu CH, Yoshino T, Douillard JY. Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO. Ann Oncol, 31:334-351, 2020
19. Takashima K, Fujii S, Komatsuzaki R, Komatsu M, Takahashi M, Kojima T, Daiko H, Minashi K, Chiwaki F, Muto M, Sasaki H, Yano T. CD24 and CK4 are upregulated by SIM2, and are predictive biomarkers for chemoradiotherapy and surgery in esophageal cancer. Int J Oncol, 56:835-847, 2020
20. Doi T, Aramaki T, Yasui H, Muro K, Ikeda M, Okusaka T, Inaba Y, Nakai K, Ikezawa H, Nakajima R. A phase I study of ontuxizumab, a humanized monoclonal antibody targeting endosialin, in Japanese patients with solid tumors. Invest New Drugs, 37:1061-1074, 2019
21. Nambu M, Masuda T, Ito S, Kato K, Kojima T, Daiko H, Ito Y, Honda K, Ohtsuki S. Leucine-Rich Alpha-2-Glycoprotein 1 in Serum Is a Possible Biomarker to Predict Response to Preoperative Chemoradiotherapy for Esophageal Cancer. Biol Pharm Bull, 42:1766-1771, 2019
22. Doi T, Fujiwara Y, Matsubara N, Tomomatsu J, Iwasa S, Tanaka A, Endo-Tsukude C, Nakagawa S, Takahashi S. Phase I study of ipatasertib as a single agent and in combination with abiraterone plus prednisolone in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol, 84:393-404, 2019
23. Doi T, Iwasa S, Muro K, Satoh T, Hironaka S, Esaki T, Nishina T, Hara H, Machida N, Komatsu Y, Shimada Y, Otsu S, Shimizu S, Watanabe M. Phase 1 trial of avelumab (anti-PD-L1) in Japanese patients with advanced solid tumors, including dose expansion in patients with gastric or gastroesophageal junction cancer: the JAVELIN Solid Tumor JPN trial. Gastric Cancer, 22:817-827, 2019
24. Doi T, Muro K, Ishii H, Kato T, Tsushima T, Takenoyama M, Oizumi S, Gemmoto K, Suna H, Enokitani K, Kawakami T, Nishikawa H, Yamamoto N. A Phase I Study of the Anti-CC Chemokine Receptor 4 Antibody, Mogamulizumab, in Combination with Nivolumab in Patients with Advanced or Metastatic Solid Tumors. Clin Cancer Res, 25:6614-6622, 2019
25. Shitara K, Iwata H, Takahashi S, Tamura K, Park H, Modi S, Tsurutani J, Kadowaki S, Yamaguchi K, Iwasa S, Saito K, Fujisaki Y, Sugihara M, Shahidi J, Doi T. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Lancet Oncol, 20:827-836, 2019
26. Shitara K, Satoh T, Iwasa S, Yamaguchi K, Muro K, Komatsu Y, Nishina T, Esaki T, Hasegawa J, Kakurai Y, Kamiyama E, Nakata T, Nakamura K, Sakaki H, Hyodo I. Safety, tolerability, pharmacokinetics, and pharmacodynamics of the afucosylated, humanized anti-EPHA2 antibody DS-8895a: a first-in-human phase I dose escalation and dose expansion study in patients with advanced solid tumors. J Immunother Cancer, 7:219, 2019
27. Yamada Y, Boku N, Mizusawa J, Iwasa S, Kadowaki S, Nakayama N, Azuma M, Sakamoto T, Shitara K, Tamura T, Chin K, Hata H, Nakamori M, Hara H, Yasui H, Katayama H, Fukuda H, Yoshikawa T, Sasako M, Terashima M. Docetaxel plus cisplatin and S-1 versus cisplatin and S-1 in patients with advanced gastric cancer (JCOG1013): an open-label, phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol, 4:501-510, 2019
28. Yoshino T, Kotaka M, Shinozaki K, Touyama T, Manaka D, Matsui T, Ishigure K, Hasegawa J, Inoue K, Munemoto Y, Takagane A, Ishikawa H, Ishida H, Ogata Y, Oba K, Goto K, Sakamoto J, Maehara Y, Ohtsu A. JOIN trial: treatment outcome and recovery status of peripheral sensory neuropathy during a 3-year follow-up in patients receiving modified FOLFOX6 as adjuvant treatment for stage II/III colon cancer. Cancer Chemother Pharmacol, 84:1269-1277, 2019
29. Doi T, Yoh K, Shitara K, Takahashi H, Ueno M, Kobayashi S, Morimoto M, Okusaka T, Ueno H, Morizane C, Okano N, Nagashima F, Furuse J. First-in-human phase 1 study of novel dUTPase inhibitor TAS-114 in combination with S-1 in Japanese patients with advanced solid tumors. Invest New Drugs, 37:507-518, 2019
30. Esaki T, Hirai F, Makiyama A, Seto T, Bando H, Naito Y, Yoh K, Ishihara K, Kakizume T, Natsume K, Myers A, Doi T. Phase I dose-escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors. Cancer Sci, 110:1340-1351, 2019
31. Bando H, Kagawa Y, Kato T, Akagi K, Denda T, Nishina T, Komatsu Y, Oki E, Kudo T, Kumamoto H, Yamanaka T, Yoshino T. A multicentre, prospective study of plasma circulating tumour DNA test for detecting RAS mutation in patients with metastatic colorectal cancer. Br J Cancer, 120:982-986, 2019
32. Shitara K, Yodo Y, Iino S. A Phase I Study of Napabucasin Plus Paclitaxel for Japanese Patients With Advanced/Recurrent Gastric Cancer. In Vivo, 33:933-937, 2019
33. Kawazoe A, Shitara K. Next-generation sequencing and biomarkers for gastric cancer: what is the future? Ther Adv Med Oncol, 11:1758835919848189, 2019
34. Sasaki A, Nakamura Y, Mishima S, Kawazoe A, Kuboki Y, Bando H, Kojima T, Doi T, Ohtsu A, Yoshino T, Kuwata T, Akimoto T, Shitara K. Predictive factors for hyperprogressive disease during nivolumab as anti-PD1 treatment in patients with advanced gastric cancer. Gastric Cancer, 22:793-802, 2019
35. Ishii T, Kawazoe A, Shitara K. Dawn of precision medicine on gastric cancer. Int J Clin Oncol, 24:779-788, 2019
36. Shitara K, Ueha S, Shichino S, Aoki H, Ogiwara H, Nakatsura T, Suzuki T, Shimomura M, Yoshikawa T, Shoda K, Kitano S, Yamashita M, Nakayama T, Sato A, Kuroda S, Wakabayashi M, Nomura S, Yokochi S, Ito S, Matsushima K, Doi T. First-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody, in patients with advanced solid tumors. J Immunother Cancer., 7:195, 2019
37. Nakamura Y, Sawada K, Fujii S, Yoshino T. HER2-targeted therapy should be shifted towards an earlier line for patients with anti-EGFR-therapy na?ve, HER2-amplified metastatic colorectal cancer. ESMO Open, 4:e000530, 2019
38. Koganemaru S, Kuboki Y, Koga Y, Kojima T, Yamauchi M, Maeda N, Kagari T, Hirotani K, Yasunaga M, Matsumura Y, Doi T. U3-1402, a Novel HER3-Targeting Antibody-Drug Conjugate, for the Treatment of Colorectal Cancer. Mol Cancer Ther, 18:2043-2050, 2019
39. Doi T, Kurokawa Y, Sawaki A, Komatsu Y, Ozaka M, Takahashi T, Naito Y, Ohkubo S, Nishida T. Efficacy and safety of TAS-116, an oral inhibitor of heat shock protein 90, in patients with metastatic or unresectable gastrointestinal stromal tumour refractory to imatinib, sunitinib and regorafenib: a phase II, single-arm trial. Eur J Cancer, 121:29-39, 2019
40. Kotani D, Kuboki Y, Horasawa S, Kaneko A, Nakamura Y, Kawazoe A, Bando H, Taniguchi H, Shitara K, Kojima T, Tsuji A, Yoshino T. Retrospective cohort study of trifluridine/tipiracil (TAS-102) plus bevacizumab versus trifluridine/tipiracil monotherapy for metastatic colorectal cancer. BMC Cancer, 19:1253, 2019
41. Hamaguchi T, Denda T, Kudo T, Sugimoto N, Ura T, Yamazaki K, Fujii H, Kajiwara T, Nakajima TE, Takahashi S, Otsu S, Komatsu Y, Nagashima F, Moriwaki T, Esaki T, Sato T, Itabashi M, Oki E, Sasaki T, Chiron M, Yoshino T. Exploration of potential prognostic biomarkers in aflibercept plus FOLFIRI in Japanese patients with metastatic colorectal cancer. Cancer Sci, 110:3565-3572, 2019
42. Kato K, Shah MA, Enzinger P, Bennouna J, Shen L, Adenis A, Sun JM, Cho BC, Özgüroğlu M, Kojima T, Kostorov V, Hierro C, Zhu Y, McLean LA, Shah S, Doi T. KEYNOTE-590: Phase III study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer. Future Oncol, 15:1057-1066, 2019
43. Masuishi T, Taniguchi H, Kotani D, Bando H, Komatsu Y, Shinozaki E, Nakajima TE, Satoh T, Nishina T, Esaki T, Wakabayashi M, Nomura S, Takahashi K, Ono H, Hirano N, Fujishiro N, Fuse N, Sato A, Ohtsu A, Yoshino T. Rationale and design of the BRAVERY study (EPOC1701): a multicentre phase II study of eribulin in patients with BRAF V600E mutant metastatic colorectal cancer. ESMO Open, 4:e000590, 2019
44. Harding JJ, Bauer TM, Tan DSW, Bedard PL, Rodon J, Doi T, Schnell C, Iyer V, Baffert F, Radhakrishnan R, Fabre C, Juric D. Characterization and phase I study of CLR457, an orally bioavailable pan-class I PI3-kinase inhibitor. Invest New Drugs, 37:271-281, 2019
45. Kamada T, Togashi Y, Tay C, Ha D, Sasaki A, Nakamura Y, Sato E, Fukuoka S, Tada Y, Tanaka A, Morikawa H, Kawazoe A, Kinoshita T, Shitara K, Sakaguchi S, Nishikawa H. PD-1+ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Proc Natl Acad Sci U S A, 116:9999-10008, 2019
46. Honda K, Gyawali B, Ando M, Kumanishi R, Kato K, Sugiyama K, Mitani S, Masuishi T, Narita Y, Bando H, Taniguchi H, Kadowaki S, Ura T, Muro K. Prospective Survey of Financial Toxicity Measured by the Comprehensive Score for Financial Toxicity in Japanese Patients With Cancer. J Glob Oncol, 5:1-8, 2019
47. Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, Sagara Y, Doi T, Park H, Murthy RK, Redman RA, Jikoh T, Lee C, Sugihara M, Shahidi J, Yver A, Modi S. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol, 20:816-826, 2019
48. Van Cutsem E, Huijberts S, Grothey A, Yaeger R, Cuyle PJ, Elez E, Fakih M, Montagut C, Peeters M, Yoshino T, Wasan H, Desai J, Ciardiello F, Gollerkeri A, Christy-Bittel J, Maharry K, Sandor V, Schellens JHM, Kopetz S, Tabernero J. Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients With BRAF V600E-Mutant Metastatic Colorectal Cancer: Safety Lead-In Results From the Phase III BEACON Colorectal Cancer Study. J Clin Oncol, 37:1460-1469, 2019
49. Togashi Y, Shitara K, Nishikawa H. Regulatory T cells in cancer immunosuppression - implications for anticancer therapy. Nat Rev Clin Oncol, 16:356-371, 2019
50. Bang YJ, Kang YK, Catenacci DV, Muro K, Fuchs CS, Geva R, Hara H, Golan T, Garrido M, Jalal SI, Borg C, Doi T, Yoon HH, Savage MJ, Wang J, Dalal RP, Shah S, Wainberg ZA, Chung HC. Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer, 22:828-837, 2019
51. Yamaguchi K, Komatsu Y, Satoh T, Uetake H, Yoshino T, Nishida T, Yamazaki N, Takikawa H, Morimoto T, Chosa M, Sunaya T, Hamada Y, Muro K, Sugihara K. Large-Scale, Prospective Observational Study of Regorafenib in Japanese Patients with Metastatic Colorectal Cancer in a Real-World Clinical Setting. Oncologist, 24:e450-e457, 2019
52. Yoshikawa T, Muro K, Shitara K, Oh DY, Kang YK, Chung HC, Kudo T, Chin K, Kadowaki S, Hamamoto Y, Hironaka S, Yoshida K, Yen CJ, Omuro Y, Bai LY, Maeda K, Ozeki A, Yoshikawa R, Kitagawa Y. Effect of First-line S-1 Plus Oxaliplatin With or Without Ramucirumab Followed by Paclitaxel Plus Ramucirumab on Advanced Gastric Cancer in East Asia: The Phase 2 RAINSTORM Randomized Clinical Trial. JAMA Netw Open, 2:e198243, 2019
53. Kaito A, Kuwata T, Tokunaga M, Shitara K, Sato R, Akimoto T, Kinoshita T. HER2 heterogeneity is a poor prognosticator for HER2-positive gastric cancer. World J Clin Cases, 7:1964-1977, 2019
54. Taieb J, Shi Q, Pederson L, Alberts S, Wolmark N, Van Cutsem E, de Gramont A, Kerr R, Grothey A, Lonardi S, Yoshino T, Yothers G, Sinicrope FA, Zaanan A, André T. Prognosis of microsatellite instability and/or mismatch repair deficiency stage III colon cancer patients after disease recurrence following adjuvant treatment: results of an ACCENT pooled analysis of seven studies. Ann Oncol, 30:1466-1471, 2019
55. Pietrantonio F, Yaeger R, Schrock AB, Randon G, Romero-Cordoba S, Rossini D, Fucà G, Ross JS, Kotani D, Madison R. Atypical RAS Mutations in Metastatic Colorectal Cancer. JCO Precision Oncology, 3:1-11, 2019
56. Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Tarpgaard LS, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med, 381:1632-1643, 2019
57. Fujii S, Yoshino T, Yamazaki K, Muro K, Yamaguchi K, Nishina T, Yuki S, Shinozaki E, Shitara K, Bando H, Mimaki S, Nakai C, Matsushima K, Suzuki Y, Akagi K, Yamanaka T, Nomura S, Esumi H, Sugiyama M, Nishida N, Mizokami M, Koh Y, Abe Y, Ohtsu A, Tsuchihara K. Histopathological factors affecting the extraction of high quality genomic DNA from tissue sections for next-generation sequencing. Biomed Rep, 11:171-180, 2019
58. Masuishi T, Yamaguchi R, Kato S, Yoshino T, Ebi H. Evaluation of ALK fusion newly identified in colon cancer by a comprehensive genomic analysis. JCO Precision Oncology, 3:2019
59. Lenz HJ, Argiles G, Yoshino T, Lonardi S, Falcone A, Limón ML, Sobrero A, Hastedt C, Peil B, Voss F, Griebsch I, Van Cutsem E. Health-related Quality of Life in the Phase III LUME-Colon 1 Study: Comparison and Interpretation of Results From EORTC QLQ-C30 Analyses. Clin Colorectal Cancer, 18:269-279.e5, 2019
60. Yaeger R, Kotani D, Mondaca S, Parikh AR, Bando H, Van Seventer EE, Taniguchi H, Zhao H, Thant CN, de Stanchina E, Rosen N, Corcoran RB, Yoshino T, Yao Z, Ebi H. Response to Anti-EGFR Therapy in Patients with BRAF non-V600-Mutant Metastatic Colorectal Cancer. Clin Cancer Res, 25:7089-7097, 2019
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