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Review

Second line treatment options for pancreatic cancer

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Pages 1607-1617 | Received 18 May 2017, Accepted 17 Aug 2017, Published online: 06 Oct 2017

References

  • 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;15:2403–2413.
  • 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;25:1960–1966.
  • Saif MW. Revising you the staging for pancreatic cancer in 2012. JOP. 2012 Mar 10;13(2):128–130.
  • Howlader N, Noone AM, Krapcho M, et al. SEER Cancer statistics review, 1975-2014. Bethesda (MD): National Cancer Institute. Available from: https://seer.cancer.gov/csr/1975_2014/ based on November 2016 SEER data submission, posted to the SEER web site, April 2017.
  • Kindler HL, Niedzwiecki D, Hollis D, et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol. 2010 Aug 1;28(22):3617–3622.
  • Philip PA, Benedetti J, Corless CL, et al. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol. 2010 Aug 1;28(22):3605–3610.
  • Gonçalves A, Gilabert M, François E, et al. BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer. Ann Oncol. 2012 Nov;23(11):2799–2805.
  • Van Cutsem E, Vervenne WL, Bennouna J, et al. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol. 2009 May 1;27(13):2231–2237.
  • Heinemann V, Vehling-Kaiser U, Waldschmidt D, et al. Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the ‘Arbeitsgemeinschaft Internistische Onkologie’ (AIO-PK0104). Gut. 2013 May;62(5):751–759.
  • Cunningham D, Chau I, Stocken DD, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009 Nov 20;27(33):5513–5518.
  • Conroy T, Desseigne F, Ychou M, et al. Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817–1825.
  • Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–1703.
  • Pelzer U, Schwaner I, Stieler J, et al. Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer. 2011;47:1676–1681.
  • Teo MY, McDermott RS. Activity and survival benefit of second-line chemotherapy (2L-Ctx) in advanced pancreatic adenocarcinoma (APC): pooled analysis of the literature. J Clin Oncol. 2013;31. (suppl; abstr e15019).
  • Oettle H, Riess H, Stieler JM, et al. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the 540 CONKO-003 trial. J Clin Oncol. 2014 Aug 10;32(23):2423–2429.
  • Gill S, Ko YJ, Cripps C, et al. PANCREOX: A randomized phase III study of 5-fluorouracil/leucovorin with or without oxaliplatin for second-line advanced pancreatic cancer in patients who have received gemcitabine-based chemotherapy. J Clin Oncol. 2016 Sep 12.
  • NAPOLI-1 Study Group. Wang-Gillam A, Li CP, Bodoky G. et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016 Feb 6; 387(10018): 545–557.
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT02923921, Study of AM0010 with FOLFOX compared to FOLFOX alone second-line Tx in Pts with metastatic pancreatic cancer; 2016 Sep 30. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT02923921
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT01954992, glufosfamide versus 5-FU in second line metastatic pancreatic cancer; 2013 Sept 27. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT01954992
  • Jayavalsan SP, Schmidt SL, Durkal V, et al. Can response to treatment predict outcome in patients with metastatic pancreatic adenocarcinoma (MPAC)? J Clin Oncol 2016;34. (suppl 4S; abstr 443).
  • Vienot A, Beinse G, Louvet C, et al. Development and validation of a prognostic nomogram and score to predict overall survival and usefulness of second-line chemotherapy in advanced pancreatic adenocarcinoma. J Clin Oncol 2017;35. (suppl 4S; abstract 354).
  • Pokataev I, Popova A, Tryakin A, et al. Clinical predictors of second-line chemotherapy benefit in patients with pancreatic cancer. JOP J Pancreas (Online). 2017 May 30;18(3):277–282.
  • Ettrich TJ, Perkhofer L, Von Wichert G, et al. DocOx (AIO-PK0106): a phase II trial of docetaxel and oxaliplatin as a second line systemic therapy in patients with advanced pancreatic ductal adenocarcinoma. BMC Cancer. 2016 Jan 15;16:21.
  • Chiorean EG, Dragovich T, Hamm J, et al. A phase 2 trial of glufosfamide in combination with gemcitabine in chemotherapy-naive pancreatic adenocarcinoma. Am J Clin Oncol. 2010 Apr;33(2):111–116.
  • Ciuleanu TE, Pavlovsky AV, Bodoky G, et al. A randomised Phase III trial of glufosfamide compared with best supportive care in metastatic pancreatic adenocarcinoma previously treated with gemcitabine. Eur J Cancer. 2009 Jun;45(9):1589–1596.
  • Mawad R, Becker PS, Hendrie P, et al. Phase II study of tosedostat with cytarabine or decitabine in newly diagnosed older patients with acute myeloid leukaemia or high-risk MDS. Br J Haematol. 2016 Jan;172(2):238–245.
  • Wickström M, Larsson R, Nygren P, et al. Aminopeptidase N (CD13) as a target for cancer chemotherapy. Cancer Sci. 2011 Mar;102(3):501–508.
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT02352831, tosedostat with capecitabine in patients with metastatic pancreatic adenocarcinoma; 2015 Jan 28. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT02352831
  • Wang-Gillam A, Du L, Teague AS, et al. A phase I/II study combining tosedostat with capecitabine in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). J Clin Oncol 2017;35. (suppl 4S; abstract 410).
  • Fukuda A, Wang SC, Morris JP 4th, et al. Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression. Cancer Cell. 2011 Apr 12;19(4):441–455.
  • Hurwitz HI, Uppal N, Wagner SA, et al. Randomized, double-blind, phase II study of ruxolitinib or placebo in combination with capecitabine in patients with metastatic pancreatic cancer for whom therapy with gemcitabine has failed. J Clin Oncol. 2015 Dec 1;33(34):4039–4047.
  • Hurwitz H, Cutsem EV, Bendell JC, et al. Two randomized, placebo-controlled phase 3 studies of ruxolitinib (Rux) + capecitabine (C) in patients (pts) with advanced/metastatic pancreatic cancer (mPC) after failure/intolerance of first-line chemotherapy: JANUS 1 (J1) and JANUS 2 (J2). J Clin Oncol 2017;35. (suppl 4S; abstract 343).
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT02042378, a study of rucaparib in patients with pancreatic cancer and a known deleterious BRCA mutation 2014 Jan 20. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT02042378
  • Domchek SM, Hendifar AE, McWilliams RR, et al. RUCAPANC: an open-label, phase 2 trial of the PARP inhibitor rucaparib in patients (pts) with pancreatic cancer (PC) and a known deleterious germline or somatic BRCA mutation. J Clin Oncol 2016;34. (suppl; abstr 4110).
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT01489865, ABT-888 with modified FOLFOX6 in patients with metastatic pancreatic cancer; 2011 Dec 8. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT01489865
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT02890355. FOLFIRI or modified FOLFIRI and veliparib as second line therapy in treating patients with metastatic pancreatic cancer. 2016 Aug 21. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT02890355
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT01585805. Gemcitabine hydrochloride and cisplatin with or without veliparib or veliparib alone in treating patients with locally advanced or metastatic pancreatic cancer. 2012 Apr 25. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT01585805
  • Chung MJ, Park JY, Bang S, et al. Phase II clinical trial of ex vivo-expanded cytokine-induced killer cells therapy in advanced pancreatic cancer. Cancer Immunol Immunother. 2014 Sep;63(9):939–946.
  • 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 Apr 20;33(12):1325–1333.
  • Le DT, Ko AH, Wainberg ZA, et al. Results from a phase 2b, randomized, multicenter study of GVAX pancreas and CRS-207 compared to chemotherapy in adults with previously-treated metastatic pancreatic adenocarcinoma (ECLIPSE Study). J Clin Oncol 2017;35. (suppl 4S; abstract 345).
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT02243371, GVAX pancreas vaccine (With CY) and CRS-207 with or without nivolumab; 2014 Sept 15. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT02243371
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT00836407, ipilimumab ± vaccine therapy in treating patients with locally advanced, unresectable or metastatic pancreatic cancer; 2009 Feb 3. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT00836407
  • Hecht JR, Naing A, Falchook G, et al. Phase 1b study with PEGylated human IL-10 (AM0010) with 5-FU and oxaliplatin (FOLFOX) in metastatic pancreatic adenocarcinoma (PDAC). J Clin Oncol 2017;35. (suppl 4S; abstract 399).
  • 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 Oct;33(8):828–833.
  • Mohindra NA, Kircher SM, Nimeiri HS, et al. Results of the phase Ib study of ipilimumab and gemcitabine for advanced pancreas cancer. J Clin Oncol 2015;33. (suppl; abstr e15281).
  • Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455–2465.
  • O’Reilly ME, Oh D, Lee MA, et al. A phase 2, open-label, multicenter study of durvalumab (MEDI4736) ± tremelimumab in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC): ALPS. J Clin Oncol 2016;34. (suppl; abstr TPS4150).
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT02558894. phase II study of MEDI4736 monotherapy or in combinations with tremelimumab in metastatic pancreatic ductal carcinoma. 2015 Aug 27. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT02558894
  • Overman MJ, Lopez CD, Benson AB, et al. A randomized phase 2 study of the Bruton tyrosine kinase (Btk) inhibitor acalabrutinib alone or with pembrolizumab for metastatic pancreatic cancer (mPC). J Clin Oncol 2016;34. (suppl; abstr 4130).
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT02362048. ACP-196 alone and in combination with pembrolizumab in subjects with advanced or metastatic pancreatic cancer (KEYNOTE144). 2015 Jan 28. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT02362048
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT03193190, a study of multiple immunotherapy-based treatment combinations in participants with metastatic pancreatic ductal adenocarcinoma; 2017 June 9. Bethesda (MD): National Library of Medicine (US). [cited 2017 Jul 28. Available from: https://clinicaltrials.gov/ct2/show/NCT03193190
  • Blumenschein GR, Hassan R, Moore KN, et al. Phase I study of anti-mesothelin antibody drug conjugate anetumab ravtansine (AR). J Clin Oncol 2016;34. (suppl; abstr 2509).
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT03023722, phase II anetumab ravtansine as 2nd line treatment for pancreatic cancer; 2017 Jan 13. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT03023722
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT02810418, phase II mesothelin-targeted immunotoxin LMB-100 alone or in combination with nab-paclitaxel in people with previously treated metastatic and/or locally advanced pancreatic ductal adenocarcinoma and mesothelin expressing solid tumors; 2016 June 22. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT02810418
  • Beg MS, Morse M, Patel SP, et al. A phase I/II multicenter study of the chimeric monoclonal antibody NEO102 (NPC-1C) in adults with refractory pancreatic (PC) and colorectal cancer (CC). J Clin Oncol 2015;33. (suppl 3; abstr 240).
  • ClinicalTrials.gov [Internet]. 2000 Feb 29. Identifier NCT01834235, QUILT-3.010: a study of gemcitabine and Nab-paclitaxel with or without NPC-1C to treat patients with pancreatic cancer; 2013 Apr 12. Bethesda (MD): National Library of Medicine (US). [cited 2017 May 5]. Available from: https://clinicaltrials.gov/ct2/show/NCT01834235
  • Saif MW, Eloubeidi MA, Russo S, et al. Phase I study of capecitabine with concomitant radiotherapy for patients with locally advanced pancreatic cancer: expression analysis of genes related to outcome. J Clin Oncol. 2005 Dec 1;23(34):8679–8687.
  • Nishina T, Hyodo I, Miyaike J, et al. The ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase in tumour tissues of patients with metastatic gastric cancer is predictive of the clinical response to 5ʹ-deoxy-5-fluorouridine. Eur J Cancer. 2004 Jul;40(10):1566–1571.
  • Saif MW, Kang SP, Ledbetter L, et al. Long-term survival on capecitabine in two gemcitabine refractory pancreatic cancer patients. Is there a pharmacogenetic explanation? JOP. 2007 Nov 9;8(6):799–805.
  • Spratlin J, Sangha R, Glubrecht D, et al. The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma. Clin Cancer Res. 2004 Oct 15;10(20):6956–6961.
  • Neoptolemos JP, Greenhalf W, Ghaneh P, et al. HENT1 tumor levels to predict survival of pancreatic ductal adenocarcinoma patients who received adjuvant gemcitabine and adjuvant 5FU on the ESPAC trials. J Clin Oncol 2013;31. (suppl; abstr 4006).
  • Neoptolemos JP, Stocken DD, Friess H, et al. European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004 Mar 18;350(12):1200–1210.
  • Neoptolemos JP, Stocken DD, Bassi C, et al. European Study Group for Pancreatic Cancer. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010 Sep 8;304(10):1073–1081.
  • Li D, Pant S, Ryan DP, et al. A phase II, open-label, multicenter study to evaluate the antitumor efficacy of CO-1.01 as second-line therapy for gemcitabine-refractory patients with stage IV pancreatic adenocarcinoma and negative tumor hENT1 expression. Pancreatology. 2014 Sep-Oct;14(5):398–402.
  • Saif MW, Li J, Lamb L, et al. First-in-human phase II trial of the botanical formulation PHY906 with capecitabine as second-line therapy in patients with advanced pancreatic cancer. Cancer Chemother Pharmacol. 2014 Feb;73(2):373–380.
  • Heymach J, Tran HT, Nixon AB, et al. Circulating cytokines and angiogenic factors (CAF) as markers of clinical response in the study of trametinib (T) plus gemcitabine (G) versus placebo (P) plus gemcitabine for patients (pts) with untreated metastatic adenocarcinoma of the pancreas (MEK113487). J Clin Oncol 2013;31. (suppl; abstr 4042).
  • Gayral M, Jo S, Hanoun N, et al. MicroRNAs as emerging biomarkers and therapeutic targets for pancreatic cancer. World J Gastroenterol. 2014 Aug 28;20(32):11199–11209.
  • Negoi I, Hostiuc S, Sartelli M, et al. MicroRNA-21 as a prognostic biomarker in patients with pancreatic cancer - A systematic review and meta-analysis. Am J Surg. 2017;214(3):515–524.
  • Ramanathan RK, Lee P, Seng JE, et al. Phase II study of induction therapy with gemcitabine and nab-paclitaxel followed by consolidation with mFOLFIRINOX in patients with metastatic pancreatic cancer. J Clin Oncol 2014;32. (suppl 3; abstr 224).
  • Kazim S, Malafa MP, Coppola D, et al. Selective nuclear export inhibitor KPT-330 enhances the antitumor activity of gemcitabine in human pancreatic cancer. Mol Cancer Ther. 2015 Jul;14(7):1570–1581.
  • Mei L, Du W, Ma WW. Targeting stromal microenvironment in pancreatic ductal adenocarcinoma: controversies and promises. J Gastrointest Oncol. 2016 Jun;7(3):487–494.
  • Strand MS, Pan H, Krasnick B, et al. Precision delivery of RAS-inhibiting siRNA to pancreatic cancer via peptide-based nanoparticles. J Clin Oncol 2017;35. (suppl 4S; abstract 287).
  • Bournet B, Buscail C, Muscari F, et al. Targeting KRAS for diagnosis, prognosis, and treatment of pancreatic cancer: hopes and realities. Eur J Cancer. 2016 Feb;54:75–83.
  • Van Cutsem E, Van De Velde H, Karasek P, et al. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol. 2004 Apr 15;22(8):1430–1438.
  • Bailey P, Chang DK, Nones K, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016 Mar 3;531(7592):47–52.

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