Skip to main content
Top
Published in: Journal of Gastroenterology 4/2020

Open Access 01-04-2020 | Pancreatic Cancer | Review

Recent advances in chemotherapy for pancreatic cancer: evidence from Japan and recommendations in guidelines

Authors: Takuji Okusaka, Junji Furuse

Published in: Journal of Gastroenterology | Issue 4/2020

Login to get access

Abstract

The prognosis of patients with pancreatic cancer continues to remain dismal, even though numerous trials have been conducted to establish more effective therapies in Japan and throughout the world. Recent advances in treatment have been characterized by the use of novel combinations of conventional cytotoxic chemotherapies. Especially in Japan, S-1 has become one of the most widely used cytotoxic agents for the treatment of pancreatic cancer, after clinical evidence was established of the survival benefit offered by this drug for patients with resectable or unresectable pancreatic cancer. Unfortunately, with the exception of erlotinib, no targeted treatment strategies have been approved for pancreatic cancer. However, following an increase in interest in drug development in recent years, proactive attempts have been made to develop new therapeutic strategies, including neoadjuvant chemotherapy for patients with resectable or borderline resectable pancreatic cancer, multi-agent combination chemotherapy for patients with advanced pancreatic cancer, and therapies with new targeted agents or immuno-oncologic agents for patients with pancreatic cancer bearing specific gene mutations.
Literature
3.
go back to reference Motoi F, Kosuge T, Ueno H, et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05). Jpn J Clin Oncol. 2019;49:190–4.CrossRefPubMed Motoi F, Kosuge T, Ueno H, et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05). Jpn J Clin Oncol. 2019;49:190–4.CrossRefPubMed
4.
go back to reference Unno M, Motoi F, Matsuyama Y, et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP-05). J Clin Oncol. 2019;37 (abstract 189). Unno M, Motoi F, Matsuyama Y, et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP-05). J Clin Oncol. 2019;37 (abstract 189).
5.
go back to reference Satoi S, Unno M, Motoi F, et al. The effect of neoadjuvant chemotherapy with gemcitabine and S-1 for resectable pancreatic cancer (randomized phase II/III trial; Prep-02/JSAP-05). J Clin Oncol 2019;39 (abstract 4126). Satoi S, Unno M, Motoi F, et al. The effect of neoadjuvant chemotherapy with gemcitabine and S-1 for resectable pancreatic cancer (randomized phase II/III trial; Prep-02/JSAP-05). J Clin Oncol 2019;39 (abstract 4126).
6.
go back to reference Tienhoven GV, Versteijne E, Suker M, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): a randomized, controlled, multicenter phase III trial. J Clin Oncol 2018;36 (abstract LBA4002). Tienhoven GV, Versteijne E, Suker M, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): a randomized, controlled, multicenter phase III trial. J Clin Oncol 2018;36 (abstract LBA4002).
7.
go back to reference Golcher H, Brunner TB, Witzigmann H, et al. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase II trial. Strahlenther Onkol. 2015;191:7–16.CrossRefPubMed Golcher H, Brunner TB, Witzigmann H, et al. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase II trial. Strahlenther Onkol. 2015;191:7–16.CrossRefPubMed
8.
go back to reference Casadei R, Di Marco M, Ricci C, et al. Neoadjuvant chemoradiotherapy and surgery versus surgery alone in resectable pancreatic cancer: a single-center prospective, randomized, controlled trial which failed to achieve accrual targets. J Gastrointest Surg. 2015;19:1802–12.CrossRefPubMed Casadei R, Di Marco M, Ricci C, et al. Neoadjuvant chemoradiotherapy and surgery versus surgery alone in resectable pancreatic cancer: a single-center prospective, randomized, controlled trial which failed to achieve accrual targets. J Gastrointest Surg. 2015;19:1802–12.CrossRefPubMed
9.
go back to reference Japan Pancreas Society. Clinical practice guidelines for pancreatic cancer 2016. Tokyo: Kanahara & Co, Ltd; 2016. Japan Pancreas Society. Clinical practice guidelines for pancreatic cancer 2016. Tokyo: Kanahara & Co, Ltd; 2016.
10.
go back to reference Yamaguchi K, Okusaka T, Shimizu K, et al. Clinical practice guidelines for pancreatic cancer 2016 from the Japan pancreas society: a synopsis. Pancreas. 2017;46:595–604.CrossRefPubMed Yamaguchi K, Okusaka T, Shimizu K, et al. Clinical practice guidelines for pancreatic cancer 2016 from the Japan pancreas society: a synopsis. Pancreas. 2017;46:595–604.CrossRefPubMed
12.
go back to reference Neuzillet C, Gaujoux S, Williet N, et al. Pancreatic cancer: French clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC). Dig Liver Dis. 2018;50:1257–71.CrossRefPubMed Neuzillet C, Gaujoux S, Williet N, et al. Pancreatic cancer: French clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC). Dig Liver Dis. 2018;50:1257–71.CrossRefPubMed
13.
go back to reference National Health Commission of the People's Republic of C. Chinese guidelines for diagnosis and treatment of pancreatic cancer 2018 (English version). Chin J Cancer Res. 2019;31:278–94.CrossRef National Health Commission of the People's Republic of C. Chinese guidelines for diagnosis and treatment of pancreatic cancer 2018 (English version). Chin J Cancer Res. 2019;31:278–94.CrossRef
15.
go back to reference Japan Pancreas Society. Clinical practice guidelines for pancreatic cancer 2019. Tokyo: Kanahara & Co, Ltd; 2019. Japan Pancreas Society. Clinical practice guidelines for pancreatic cancer 2019. Tokyo: Kanahara & Co, Ltd; 2019.
16.
go back to reference Okusaka T, Nakamura M, Yoshida M, et al. Clinical practice guidelines for pancreatic cancer 2019 from the Japan Pancreas Society: a Synopsis. Pancreas. 2020 (49:in press). Okusaka T, Nakamura M, Yoshida M, et al. Clinical practice guidelines for pancreatic cancer 2019 from the Japan Pancreas Society: a Synopsis. Pancreas. 2020 (49:in press).
17.
go back to reference Ajani JA, Faust J, Ikeda K, et al. Phase I pharmacokinetic study of S-1 plus cisplatin in patients with advanced gastric carcinoma. J Clin Oncol. 2005;23:6957–65.CrossRefPubMed Ajani JA, Faust J, Ikeda K, et al. Phase I pharmacokinetic study of S-1 plus cisplatin in patients with advanced gastric carcinoma. J Clin Oncol. 2005;23:6957–65.CrossRefPubMed
18.
go back to reference Ajani JA, Rodriguez W, Bodoky G, et al. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010;28:1547–53.CrossRefPubMed Ajani JA, Rodriguez W, Bodoky G, et al. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010;28:1547–53.CrossRefPubMed
23.
go back to reference Katz MHG, Ou FS, Herman JM, et al. Alliance for clinical trials in oncology (ALLIANCE) trial A021501: preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas. BMC Cancer. 2017;17:505. Katz MHG, Ou FS, Herman JM, et al. Alliance for clinical trials in oncology (ALLIANCE) trial A021501: preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas. BMC Cancer. 2017;17:505.
24.
go back to reference Gao S, Zhu X, Shi X, et al. Comparisons of different neoadjuvant chemotherapy regimens with or without stereotactic body radiation therapy for borderline resectable pancreatic cancer: study protocol of a prospective, randomized phase II trial (BRPCNCC-1). Radiat Oncol. 2019;14:52.CrossRefPubMedPubMedCentral Gao S, Zhu X, Shi X, et al. Comparisons of different neoadjuvant chemotherapy regimens with or without stereotactic body radiation therapy for borderline resectable pancreatic cancer: study protocol of a prospective, randomized phase II trial (BRPCNCC-1). Radiat Oncol. 2019;14:52.CrossRefPubMedPubMedCentral
28.
go back to reference Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297:267–77.CrossRefPubMed Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297:267–77.CrossRefPubMed
29.
go back to reference Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310:1473–81.CrossRefPubMed Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310:1473–81.CrossRefPubMed
30.
go back to reference Ueno H, Kosuge T, Matsuyama Y, et al. A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer. Br J Cancer. 2009;101:908–15.CrossRefPubMedPubMedCentral Ueno H, Kosuge T, Matsuyama Y, et al. A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer. Br J Cancer. 2009;101:908–15.CrossRefPubMedPubMedCentral
31.
go back to reference Neoptolemos JP, Moore MJ, Cox TF, et al. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA. 2012;308:147–56.CrossRefPubMed Neoptolemos JP, Moore MJ, Cox TF, et al. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA. 2012;308:147–56.CrossRefPubMed
32.
go back to reference Uesaka K, Boku N, Fukutomi A, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016;388:248–57.CrossRefPubMed Uesaka K, Boku N, Fukutomi A, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016;388:248–57.CrossRefPubMed
33.
go back to reference Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389:1011–24.CrossRefPubMed Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389:1011–24.CrossRefPubMed
34.
go back to reference Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379:2395–406.CrossRefPubMed Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379:2395–406.CrossRefPubMed
35.
go back to reference Tempero MA, Reni M, Riess H, et al. APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma. J Clin Oncol. 2019;37 (abstract 4000). Tempero MA, Reni M, Riess H, et al. APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma. J Clin Oncol. 2019;37 (abstract 4000).
36.
go back to reference Ioka T, Fukutomi A, Mizusawa J, et al. Randomized phase II study of S-1 and concurrent radiotherapy with versus without induction chemotherapy of gemcitabine for locally advanced pancreatic cancer (LAPC): final analysis of JCOG1106. Ann Oncol. 2016;27 (abstract 621PD). Ioka T, Fukutomi A, Mizusawa J, et al. Randomized phase II study of S-1 and concurrent radiotherapy with versus without induction chemotherapy of gemcitabine for locally advanced pancreatic cancer (LAPC): final analysis of JCOG1106. Ann Oncol. 2016;27 (abstract 621PD).
37.
go back to reference Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.CrossRefPubMed Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.CrossRefPubMed
38.
go back to reference Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703.CrossRef Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703.CrossRef
39.
go back to reference Mizusawa J, Fukutomi A, Katayama H, et al. Protocol digest of randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan clinical oncology group study (JCOG1407). Pancreatology. 2018;18:841–5.CrossRefPubMed Mizusawa J, Fukutomi A, Katayama H, et al. Protocol digest of randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan clinical oncology group study (JCOG1407). Pancreatology. 2018;18:841–5.CrossRefPubMed
40.
go back to reference Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.CrossRefPubMed Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.CrossRefPubMed
41.
go back to reference Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25:1960–6.CrossRefPubMed Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25:1960–6.CrossRefPubMed
42.
go back to reference Okada S, Ueno H, Okusaka T, et al. Phase I trial of gemcitabine in patients with advanced pancreatic cancer. Jpn J Clin Oncol. 2001;31:7–12.CrossRefPubMed Okada S, Ueno H, Okusaka T, et al. Phase I trial of gemcitabine in patients with advanced pancreatic cancer. Jpn J Clin Oncol. 2001;31:7–12.CrossRefPubMed
43.
go back to reference Okusaka T, Furuse J, Funakoshi A, et al. Phase II study of erlotinib plus gemcitabine in Japanese patients with unresectable pancreatic cancer. Cancer Sci. 2011;102:425–31.CrossRefPubMed Okusaka T, Furuse J, Funakoshi A, et al. Phase II study of erlotinib plus gemcitabine in Japanese patients with unresectable pancreatic cancer. Cancer Sci. 2011;102:425–31.CrossRefPubMed
44.
go back to reference Okusaka T, Ikeda M, Fukutomi A, et al. Phase II study of FOLFIRINOX for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. Cancer Sci. 2014;105:1321–6.CrossRefPubMedPubMedCentral Okusaka T, Ikeda M, Fukutomi A, et al. Phase II study of FOLFIRINOX for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. Cancer Sci. 2014;105:1321–6.CrossRefPubMedPubMedCentral
45.
go back to reference Ueno H, Ikeda M, Ueno M, et al. Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. Cancer Chemother Pharmacol. 2016;77:595–603.CrossRefPubMed Ueno H, Ikeda M, Ueno M, et al. Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. Cancer Chemother Pharmacol. 2016;77:595–603.CrossRefPubMed
46.
go back to reference Ueno H, Ioka T, Ikeda M, et al. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013;31:1640–8.CrossRefPubMed Ueno H, Ioka T, Ikeda M, et al. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013;31:1640–8.CrossRefPubMed
47.
go back to reference Okusaka T, Miyakawa H, Fujii H, et al. Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer. J Cancer Res Clin Oncol. 2017;143:1053–9.CrossRefPubMedPubMedCentral Okusaka T, Miyakawa H, Fujii H, et al. Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer. J Cancer Res Clin Oncol. 2017;143:1053–9.CrossRefPubMedPubMedCentral
48.
go back to reference Schultheis B, Strumberg D, Bergmann L, et al. Results of a phase II trial of S-1 as first-line treatment of metastatic pancreatic cancer (CESAR-study group). Invest New Drugs. 2012;30:1184–92.CrossRefPubMed Schultheis B, Strumberg D, Bergmann L, et al. Results of a phase II trial of S-1 as first-line treatment of metastatic pancreatic cancer (CESAR-study group). Invest New Drugs. 2012;30:1184–92.CrossRefPubMed
49.
go back to reference Demetri GD, Paz-Ares L, Farago AF, et al. Efficacy and safety of entrectinib in patients with NTRK fusion-positive tumours: Pooled analysis of STARTRK-2, STARTRK-1, and ALKA-372-001. Ann Oncol. 2018;29 (abstract LBA4). Demetri GD, Paz-Ares L, Farago AF, et al. Efficacy and safety of entrectinib in patients with NTRK fusion-positive tumours: Pooled analysis of STARTRK-2, STARTRK-1, and ALKA-372-001. Ann Oncol. 2018;29 (abstract LBA4).
51.
go back to reference Royal RE, Levy C, Turner K, et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010;33:828–33.CrossRefPubMedPubMedCentral Royal RE, Levy C, Turner K, et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010;33:828–33.CrossRefPubMedPubMedCentral
52.
53.
go back to reference O'Reilly EM, Oh DY, Dhani N, et al. Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: a phase 2 randomized clinical Trial. JAMA Oncol. 2019. [Epub ahead of print] O'Reilly EM, Oh DY, Dhani N, et al. Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: a phase 2 randomized clinical Trial. JAMA Oncol. 2019.  [Epub ahead of print]
54.
go back to reference Wainberg ZA, Hochster HS, Edward Jae-Hoon Kim, et al. Phase I study of nivolumab (Nivo) + nab-paclitaxel (nab-P) + gemcitabine (Gem) in advanced pancreatic cancer (APC). J Clin Oncol. 2019;37 (abstract 298). Wainberg ZA, Hochster HS, Edward Jae-Hoon Kim, et al. Phase I study of nivolumab (Nivo) + nab-paclitaxel (nab-P) + gemcitabine (Gem) in advanced pancreatic cancer (APC). J Clin Oncol. 2019;37 (abstract 298).
55.
go back to reference Weiss GJ, Blaydorn L, Beck J, et al. Phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma. Invest New Drugs. 2018;36:96–102.CrossRefPubMed Weiss GJ, Blaydorn L, Beck J, et al. Phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma. Invest New Drugs. 2018;36:96–102.CrossRefPubMed
57.
go back to reference Chung HC, Ros W, Delord JP, et al. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2019;37:1470–8.CrossRefPubMed Chung HC, Ros W, Delord JP, et al. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2019;37:1470–8.CrossRefPubMed
59.
go back to reference Doi T, Muro K, Ishii H, et al. 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. 2019;25:6614–22. Doi T, Muro K, Ishii H, et al. 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. 2019;25:6614–22.
60.
go back to reference Carleton M, Powers J, Phillips P, et al. Pharmacodynamics (PD) and genomic profiling of pts treated with cabiralizumab (cabira) + nivolumab (NIVO) provide evidence of on-target tumor immune modulations and support future clinical applications. J Clin Oncol 2018;36 (abstract 3020). Carleton M, Powers J, Phillips P, et al. Pharmacodynamics (PD) and genomic profiling of pts treated with cabiralizumab (cabira) + nivolumab (NIVO) provide evidence of on-target tumor immune modulations and support future clinical applications. J Clin Oncol 2018;36 (abstract 3020).
61.
go back to reference Wainberg ZA, Piha-Paul SA, Luke J, et al. First-in-human phase 1 dose escalation and expansion of a novel combination, anti–CSF-1 receptor (cabiralizumab) plus anti-PD-1 (nivolumab), in patients with advanced solid tumors. J Immunother Cancer. 2017;5 (abstract O42) Wainberg ZA, Piha-Paul SA, Luke J, et al. First-in-human phase 1 dose escalation and expansion of a novel combination, anti–CSF-1 receptor (cabiralizumab) plus anti-PD-1 (nivolumab), in patients with advanced solid tumors. J Immunother Cancer. 2017;5 (abstract O42)
62.
go back to reference Wang-Gillam A, O'Reilly EM, Bendell JC, et al. A randomized phase II study of cabiralizumab (cabira) + nivolumab (nivo) ± chemotherapy (chemo) in advanced pancreatic ductal adenocarcinoma (PDAC). J Clin Oncol 2019;37 (abstract TPS465). Wang-Gillam A, O'Reilly EM, Bendell JC, et al. A randomized phase II study of cabiralizumab (cabira) + nivolumab (nivo) ± chemotherapy (chemo) in advanced pancreatic ductal adenocarcinoma (PDAC). J Clin Oncol 2019;37 (abstract TPS465).
63.
go back to reference Strauss J, Heery CR, Schlom J, et al. Phase I trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGFbeta, in advanced solid tumors. Clin Cancer Res. 2018;24:1287–95.CrossRefPubMedPubMedCentral Strauss J, Heery CR, Schlom J, et al. Phase I trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGFbeta, in advanced solid tumors. Clin Cancer Res. 2018;24:1287–95.CrossRefPubMedPubMedCentral
64.
go back to reference Reiss KA, Mick R, O'Hara MH, et al. A randomized phase II trial of niraparib plus either nivolumab or ipilimumab in patients with advanced pancreatic cancer whose cancer has not progressed on platinum-based therapy. J Clin Oncol 2019;37 (abstract TPS4161). Reiss KA, Mick R, O'Hara MH, et al. A randomized phase II trial of niraparib plus either nivolumab or ipilimumab in patients with advanced pancreatic cancer whose cancer has not progressed on platinum-based therapy. J Clin Oncol 2019;37 (abstract TPS4161).
65.
go back to reference Desai J, Kortmansky JS, Segal NH, et al. MORPHEUS: A phase Ib/II study platform evaluating the safety and clinical efficacy of cancer immunotherapy (CIT)—based combinations in gastrointestinal (GI) cancers. J Clin Oncol 2019;37 (abstract TPS467). Desai J, Kortmansky JS, Segal NH, et al. MORPHEUS: A phase Ib/II study platform evaluating the safety and clinical efficacy of cancer immunotherapy (CIT)—based combinations in gastrointestinal (GI) cancers. J Clin Oncol 2019;37 (abstract TPS467).
66.
go back to reference Wang-Gillam A, Lockhart AC, Tan BR, et al. Phase I study of defactinib combined with pembrolizumab and gemcitabine in patients with advanced cancer. J Clin Oncol 2018;36 (abstract 2561). Wang-Gillam A, Lockhart AC, Tan BR, et al. Phase I study of defactinib combined with pembrolizumab and gemcitabine in patients with advanced cancer. J Clin Oncol 2018;36 (abstract 2561).
67.
go back to reference Shima H, Tsurita G, Wada S, et al. Randomized phase II trial of survivin 2B peptide vaccination for patients with HLA-A24-positive pancreatic adenocarcinoma. Cancer Sci. 2019;110:2378–85.PubMedPubMedCentral Shima H, Tsurita G, Wada S, et al. Randomized phase II trial of survivin 2B peptide vaccination for patients with HLA-A24-positive pancreatic adenocarcinoma. Cancer Sci. 2019;110:2378–85.PubMedPubMedCentral
68.
go back to reference Yamaue H, Tsunoda T, Tani M, et al. Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer: PEGASUS-PC Study. Cancer Sci. 2015;106:883–90.CrossRefPubMedPubMedCentral Yamaue H, Tsunoda T, Tani M, et al. Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer: PEGASUS-PC Study. Cancer Sci. 2015;106:883–90.CrossRefPubMedPubMedCentral
69.
go back to reference Nishida S, Ishikawa T, Egawa S, et al. Combination gemcitabine and WT1 peptide vaccination improves progression-free survival in advanced pancreatic ductal adenocarcinoma: a phase II randomized study. Cancer Immunol Res. 2018;6:320–31.CrossRefPubMed Nishida S, Ishikawa T, Egawa S, et al. Combination gemcitabine and WT1 peptide vaccination improves progression-free survival in advanced pancreatic ductal adenocarcinoma: a phase II randomized study. Cancer Immunol Res. 2018;6:320–31.CrossRefPubMed
70.
go back to reference Cheever MA, Allison JP, Ferris AS, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009;15:5323–37.CrossRefPubMedPubMedCentral Cheever MA, Allison JP, Ferris AS, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009;15:5323–37.CrossRefPubMedPubMedCentral
71.
go back to reference Katsuda M, Miyazawa M, Kawai M, et al. A phase III, double-blind, randomized clinical trial comparing S-1 in combination with DC vaccine loaded with WT1 peptides (TLP0-001) or placebo for the patients with advanced pancreatic cancer refractory to standard chemotherapy. J Clin Oncol. 2017;35 (abstract TPS4153). Katsuda M, Miyazawa M, Kawai M, et al. A phase III, double-blind, randomized clinical trial comparing S-1 in combination with DC vaccine loaded with WT1 peptides (TLP0-001) or placebo for the patients with advanced pancreatic cancer refractory to standard chemotherapy. J Clin Oncol. 2017;35 (abstract TPS4153).
72.
go back to reference Katsuda M, Miyazawa M, Ojima T, et al. A double-blind randomized comparative clinical trial to evaluate the safety and efficacy of dendritic cell vaccine loaded with WT1 peptides (TLP0-001) in combination with S-1 in patients with advanced pancreatic cancer refractory to standard chemotherapy. Trials. 2019;20:242.CrossRefPubMedPubMedCentral Katsuda M, Miyazawa M, Ojima T, et al. A double-blind randomized comparative clinical trial to evaluate the safety and efficacy of dendritic cell vaccine loaded with WT1 peptides (TLP0-001) in combination with S-1 in patients with advanced pancreatic cancer refractory to standard chemotherapy. Trials. 2019;20:242.CrossRefPubMedPubMedCentral
73.
go back to reference Kimura Y, Tsukada J, Tomoda T, et al. Clinical and immunologic evaluation of dendritic cell-based immunotherapy in combination with gemcitabine and/or S-1 in patients with advanced pancreatic carcinoma. Pancreas. 2012;41:195–205.CrossRefPubMed Kimura Y, Tsukada J, Tomoda T, et al. Clinical and immunologic evaluation of dendritic cell-based immunotherapy in combination with gemcitabine and/or S-1 in patients with advanced pancreatic carcinoma. Pancreas. 2012;41:195–205.CrossRefPubMed
74.
go back to reference Le DT, Wang-Gillam A, Picozzi V, et al. Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol. 2015;33:1325–33.CrossRefPubMedPubMedCentral Le DT, Wang-Gillam A, Picozzi V, et al. Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol. 2015;33:1325–33.CrossRefPubMedPubMedCentral
75.
go back to reference Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–48.CrossRefPubMedPubMedCentral Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–48.CrossRefPubMedPubMedCentral
76.
go back to reference Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B cell lymphoma. N Engl J Med. 2019;380:45–56.CrossRefPubMed Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B cell lymphoma. N Engl J Med. 2019;380:45–56.CrossRefPubMed
77.
go back to reference Beatty GL, O'Hara MH, Lacey SF, et al. Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial. Gastroenterology. 2018;155:29–322.CrossRefPubMed Beatty GL, O'Hara MH, Lacey SF, et al. Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial. Gastroenterology. 2018;155:29–322.CrossRefPubMed
78.
79.
go back to reference Lowery MA, Kelsen DP, Capanu M, et al. Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma. Eur J Cancer. 2018;89:19–26.CrossRefPubMed Lowery MA, Kelsen DP, Capanu M, et al. Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma. Eur J Cancer. 2018;89:19–26.CrossRefPubMed
80.
go back to reference O'Reilly EM, Lee JW, Lowery MA, et al. Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib in 2 patient cohorts: Germline BRCA mutation carriers and wild-type BRCA pancreatic ductal adenocarcinoma. Cancer. 2018;124:1374–82.CrossRefPubMed O'Reilly EM, Lee JW, Lowery MA, et al. Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib in 2 patient cohorts: Germline BRCA mutation carriers and wild-type BRCA pancreatic ductal adenocarcinoma. Cancer. 2018;124:1374–82.CrossRefPubMed
81.
go back to reference Shroff RT, Hendifar A, McWilliams RR, et al. Rucaparib monotherapy in patients with pancreatic cancer and a known deleterious BRCA mutation. JCO Precis Oncol. 2018;2018. Shroff RT, Hendifar A, McWilliams RR, et al. Rucaparib monotherapy in patients with pancreatic cancer and a known deleterious BRCA mutation. JCO Precis Oncol. 2018;2018.
82.
go back to reference Fakih M, O'Neil B, Price TJ, et al. Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRASG12C inhibitor, in advanced solid tumors. J Clin Oncol. 2019;37 (abstract 3003). Fakih M, O'Neil B, Price TJ, et al. Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRASG12C inhibitor, in advanced solid tumors. J Clin Oncol. 2019;37 (abstract 3003).
83.
go back to reference Aung KL, Fischer SE, Denroche RE, et al. Genomics-driven precision medicine for advanced pancreatic cancer: early results from the COMPASS trial. Clin Cancer Res. 2018;24:1344–54.CrossRefPubMed Aung KL, Fischer SE, Denroche RE, et al. Genomics-driven precision medicine for advanced pancreatic cancer: early results from the COMPASS trial. Clin Cancer Res. 2018;24:1344–54.CrossRefPubMed
84.
go back to reference Pishvaian MJ, Bender RJ, Halverson D, et al. Molecular profiling of patients with pancreatic cancer: initial results from the know your tumor initiative. Clin Cancer Res. 2018;24:5018–27.CrossRefPubMed Pishvaian MJ, Bender RJ, Halverson D, et al. Molecular profiling of patients with pancreatic cancer: initial results from the know your tumor initiative. Clin Cancer Res. 2018;24:5018–27.CrossRefPubMed
85.
go back to reference Hingorani SR, Zheng L, Bullock AJ, et al. HALO 202: randomized phase II study of PEGPH20 plus nab-paclitaxel/gemcitabine versus nab-paclitaxel/gemcitabine in patients with untreated, metastatic pancreatic ductal adenocarcinoma. J Clin Oncol. 2018;36:359–66.CrossRefPubMed Hingorani SR, Zheng L, Bullock AJ, et al. HALO 202: randomized phase II study of PEGPH20 plus nab-paclitaxel/gemcitabine versus nab-paclitaxel/gemcitabine in patients with untreated, metastatic pancreatic ductal adenocarcinoma. J Clin Oncol. 2018;36:359–66.CrossRefPubMed
86.
go back to reference Ramanathan RK, McDonough SL, Philip PA, et al. Phase IB/II randomized study of FOLFIRINOX plus pegylated recombinant human hyaluronidase versus FOLFIRINOX alone in patients with metastatic pancreatic adenocarcinoma: SWOG S1313. J Clin Oncol. 2019;37:1062–9.CrossRefPubMedPubMedCentral Ramanathan RK, McDonough SL, Philip PA, et al. Phase IB/II randomized study of FOLFIRINOX plus pegylated recombinant human hyaluronidase versus FOLFIRINOX alone in patients with metastatic pancreatic adenocarcinoma: SWOG S1313. J Clin Oncol. 2019;37:1062–9.CrossRefPubMedPubMedCentral
87.
go back to reference Doherty GJ, Tempero M, Corrie PG. HALO-109-301: a Phase III trial of PEGPH20 (with gemcitabine and nab-paclitaxel) in hyaluronic acid-high stage IV pancreatic cancer. Future Oncol. 2018;14:13–22.CrossRefPubMed Doherty GJ, Tempero M, Corrie PG. HALO-109-301: a Phase III trial of PEGPH20 (with gemcitabine and nab-paclitaxel) in hyaluronic acid-high stage IV pancreatic cancer. Future Oncol. 2018;14:13–22.CrossRefPubMed
89.
go back to reference Ignatiadis M, Lee M, Jeffrey SS. Circulating tumor cells and circulating tumor DNA: challenges and opportunities on the path to clinical utility. Clin Cancer Res. 2015;21:4786–800.CrossRefPubMed Ignatiadis M, Lee M, Jeffrey SS. Circulating tumor cells and circulating tumor DNA: challenges and opportunities on the path to clinical utility. Clin Cancer Res. 2015;21:4786–800.CrossRefPubMed
90.
go back to reference Lee JS, Park SS, Lee YK, et al. Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA. Mol Oncol. 2019;13:1623–50.CrossRefPubMedPubMedCentral Lee JS, Park SS, Lee YK, et al. Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA. Mol Oncol. 2019;13:1623–50.CrossRefPubMedPubMedCentral
91.
go back to reference Takai E, Totoki Y, Nakamura H, et al. Clinical utility of circulating tumor DNA for molecular assessment and precision medicine in pancreatic cancer. Adv Exp Med Biol. 2016;924:13–7.CrossRefPubMed Takai E, Totoki Y, Nakamura H, et al. Clinical utility of circulating tumor DNA for molecular assessment and precision medicine in pancreatic cancer. Adv Exp Med Biol. 2016;924:13–7.CrossRefPubMed
92.
go back to reference Mader S, Pantel K. Liquid biopsy: current status and future perspectives. Oncol Res Treat. 2017;40:404–8.CrossRefPubMed Mader S, Pantel K. Liquid biopsy: current status and future perspectives. Oncol Res Treat. 2017;40:404–8.CrossRefPubMed
Metadata
Title
Recent advances in chemotherapy for pancreatic cancer: evidence from Japan and recommendations in guidelines
Authors
Takuji Okusaka
Junji Furuse
Publication date
01-04-2020
Publisher
Springer Singapore
Published in
Journal of Gastroenterology / Issue 4/2020
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-020-01666-y

Other articles of this Issue 4/2020

Journal of Gastroenterology 4/2020 Go to the issue

Original Article—Liver, Pancreas, and Biliary Tract

Nationwide epidemiological survey of autoimmune pancreatitis in Japan in 2016

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.