2,727
Views
9
CrossRef citations to date
0
Altmetric
Original Research

Adjuvant MUC vaccination with tecemotide after resection of colorectal liver metastases: a randomized, double-blind, placebo-controlled, multicenter AIO phase II trial (LICC)

ORCID Icon, , , , , , , , , , , , , , , , , ORCID Icon, & show all
Article: 1806680 | Received 09 Mar 2020, Accepted 31 Jul 2020, Published online: 23 Aug 2020

References

  • Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol Off J Eur Soc Med Oncol. 2016;27(8):1386–10. doi:10.1093/annonc/mdw235.
  • National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Colon cancer (Version 4). (2018). https://www.nccn.org. Accessed August 1st, 2020.
  • National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Rectal cancer (Version 3). (2018). https://www.nccn.org. Accessed August 1st, 2020.
  • de Jong MC, Pulitano C, Ribero D, Strub J, Mentha G, Schulick RD, Choti MA, Aldrighetti L, Capussotti L, Pawlik TM. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009;250(3):440–448. doi:10.1097/SLA.0b013e3181b4539b.
  • Nordlinger B, Guiguet M, Vaillant JC, Balladur P, Boudjema K, Bachellier P, Jaeck D, Française de Chirurgie A. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association française de Chirurgie. Cancer. 1996;77(7):1254–1262. doi:10.1002/(SICI)1097-0142(19960401)77:7<1254::AID-CNCR5>3.0.CO;2-I.
  • Fong Y, Cohen AM, Fortner JG, Enker WE, Turnbull AD, Coit DG, Marrero AM, Prasad M, Blumgart LH, Brennan MF. Liver resection for colorectal metastases. J Clin Oncol Off J Am Soc Clin Oncol. 1997;15(3):938–946. doi:10.1200/JCO.1997.15.3.938.
  • Kato T, Yasui K, Hirai T, Kanemitsu Y, Mori T, Sugihara K, Mochizuki H, Yamamoto J. Therapeutic results for hepatic metastasis of colorectal cancer with special reference to effectiveness of hepatectomy: analysis of prognostic factors for 763 cases recorded at 18 institutions. Dis Colon Rectum. 2003;46(10Suppl):S22–31. doi:10.1097/01.DCR.0000089106.71914.00.
  • Pawlik TM, Scoggins CR, Zorzi D, Abdalla EK, Andres A, Eng C, Curley SA, Loyer EM, Muratore A, Mentha G, et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg. 2005;241(5):715–722. discussion 722-724. doi:10.1097/01.sla.0000160703.75808.7d.
  • Rees M, Tekkis PP, Welsh FKS, O’Rourke T, John TG. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg. 2008;247(1):125–135. doi:10.1097/SLA.0b013e31815aa2c2.
  • Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14(12):1208–1215. doi:10.1016/S1470-2045(13)70447-9.
  • Portier G, Elias D, Bouche O, Rougier P, Bosset J-F, Saric J, Belghiti J, Piedbois P, Guimbaud R, Nordlinger B, et al. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol Off J Am Soc Clin Oncol. 2006;24(31):4976–4982. doi:10.1200/JCO.2006.06.8353.
  • Folprecht G, Gruenberger T, Bechstein W, Raab H-R, Weitz J, Lordick F, Hartmann JT, Stoehlmacher-Williams J, Lang H, Trarbach T, et al. Survival of patients with initially unresectable colorectal liver metastases treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept (CELIM study). Ann Oncol. 2014;25(5):1018–1025. doi:10.1093/annonc/mdu088.
  • Holch JW, Ricard I, Stintzing S, Fischer von Weikersthal L, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran S-E, Heintges T, Lerchenmüller C, et al. Relevance of liver-limited disease in metastatic colorectal cancer: subgroup findings of the FIRE-3/AIO KRK0306 trial. Int J Cancer. 2018;142(5):1047–1055. doi:10.1002/ijc.31114.
  • Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet Lond Engl. 2008;371(9617):1007–1016. doi:10.1016/S0140-6736(08)60455-9.
  • Folprecht G, Gruenberger T, Bechstein WO, Raab H-R, Lordick F, Hartmann JT, Lang H, Frilling A, Stoehlmacher J, Weitz J, et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol. 2010;11(1):38–47. doi:10.1016/S1470-2045(09)70330-4.
  • Suzuki H, Shoda J, Kawamoto T, Shinozaki E, Miyahara N, Hotta S, Iizuka Y, Nakahara A, Tanaka N, Yanaka A, et al. Expression of MUC1 recognized by monoclonal antibody MY.1E12 is a useful biomarker for tumor aggressiveness of advanced colon carcinoma. Clin Exp Metastasis. 2004;21(4):321–329. doi:10.1023/B:CLIN.0000046133.35133.cc.
  • Zhang K, Tang W, Qu X, Guo Q, Inagaki Y, Seyama Y, Abe H, Gai R, Kokudo N, Sugawara Y, et al. KL-6 mucin in metastatic liver cancer tissues from primary colorectal carcinoma. Hepatogastroenterology. 2009;56(93):960–963.
  • Sangha R, Butts C. L-BLP25: a peptide vaccine strategy in non-small cell lung cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2007;13(15 Pt 2):s4652–4654. doi:10.1158/1078-0432.CCR-07-0213.
  • Zeng Y, Zhang Q, Zhang Y, Lu M, Liu Y, Zheng T, Feng S, Hao M, Shi H, Singh PK. MUC1 predicts colorectal cancer metastasis: a systematic review and meta-analysis of case controlled studies. PloS One. 2015;10(9):e0138049. doi:10.1371/journal.pone.0138049.
  • Butts C, Murray N, Maksymiuk A, Goss G, Marshall E, Soulières D, Cormier Y, Ellis P, Price A, Sawhney R, et al. Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23(27):6674–6681. doi:10.1200/JCO.2005.13.011.
  • Butts C, Socinski MA, Mitchell PL, Thatcher N, Havel L, Krzakowski M, Nawrocki S, Ciuleanu T-E, Bosquée L, Trigo JM, et al. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15(1):59–68. doi:10.1016/S1470-2045(13)70510-2.
  • Schimanski CC, Mohler M, Schon M, van Cutsem E, Greil R, Bechstein WO, Hegewisch-Becker S, von Wichert G, Vohringer M, Heike M, et al. LICC: L-BLP25 in patients with colorectal carcinoma after curative resection of hepatic metastases–a randomized, placebo-controlled, multicenter, multinational, double-blinded phase II trial. BMC Cancer. 2012;12(1):144. doi:10.1186/1471-2407-12-144.
  • Moehler M, Maderer A, Ehrlich A, Foerster F, Schad A, Nickolay T, Ruckes C, Weinmann A, Sivanathan V, Marquardt JU, et al. Safety and efficacy of afatinib as add-on to standard therapy of gemcitabine/cisplatin in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, phase I trial with an extensive biomarker program. BMC Cancer. 2019;19(1):55. doi:10.1186/s12885-018-5223-7.
  • Remmele W, Stegner HE. [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]. Pathol. 1987;8:138–140.
  • Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230(3):309–318. discussion 318-321. doi:10.1097/00000658-199909000-00004.
  • Scurr M, Pembroke T, Bloom A, Roberts D, Thomson A, Smart K, Bridgeman H, Adams R, Brewster A, Jones R, et al. Low-dose cyclophosphamide induces antitumor T-cell responses, which associate with survival in metastatic colorectal cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2017;23(22):6771–6780. doi:10.1158/1078-0432.CCR-17-0895.
  • Wang Y-J, Fletcher R, Yu J, Zhang L. Immunogenic effects of chemotherapy-induced tumor cell death. Genes Dis. 2018;5(3):194–203. doi:10.1016/j.gendis.2018.05.003.
  • Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother CII. 2007;56(5):641–648. doi:10.1007/s00262-006-0225-8.
  • Kan S, Hazama S, Maeda K, Inoue Y, Homma S, Koido S, Okamoto M, Oka M. Suppressive effects of cyclophosphamide and gemcitabine on regulatory T-cell induction in vitro. Anticancer Res. 2012;32:5363–5369.
  • Allard MA, Adam R, Giuliante F, Lapointe R, Hubert C, Ijzermans JNM, Mirza DF, Elias D, Laurent C, Gruenberger T, et al. Long-term outcomes of patients with 10 or more colorectal liver metastases. Br J Cancer. 2017;117(5):604–611. doi:10.1038/bjc.2017.218.
  • Tranchart H, Chirica M, Faron M, Balladur P, Lefevre LB, Svrcek M, de Gramont A, Tiret E, Paye F. Prognostic impact of positive surgical margins after resection of colorectal cancer liver metastases: reappraisal in the era of modern chemotherapy. World J Surg. 2013;37(11):2647–2654. doi:10.1007/s00268-013-2186-3.
  • Wang Y, Liu YF, Cheng Y, Yi DH, Li P, Song WQ, Fu DZ, Wang X. Prognosis of colorectal cancer with liver metastasis: value of a prognostic index. Braz J Med Biol Res. 2010;43(11):1116–1122. doi:10.1590/S0100-879X2010007500103.
  • Choti MA, Sitzmann JV, Tiburi MF, Sumetchotimetha W, Rangsin R, Schulick RD, Lillemoe KD, Yeo CJ, Cameron JL. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg. 2002;235(6):759–766. doi:10.1097/00000658-200206000-00002.
  • Duncan TJ, Watson NFS, Al-Attar AH, Scholefield JH, Durrant LG. The role of MUC1 and MUC3 in the biology and prognosis of colorectal cancer. World J Surg Oncol. 2007;5(1):31. doi:10.1186/1477-7819-5-31.
  • Baldus SE, Mönig SP, Huxel S, Landsberg S, Hanisch F-G, Engelmann K, Schneider PM, Thiele J, Hölscher AH, Dienes HP. MUC1 and nuclear beta-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis. Clin Cancer Res Off J Am Assoc Cancer Res. 2004;10(8):2790–2796. doi:10.1158/1078-0432.CCR-03-0163.
  • Baldus SE, Mönig SP, Hanisch F-G, Zirbes TK, Flucke U, Oelert S, Zilkens G, Madejczik B, Thiele J, Schneider PM, et al. Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl-Lewis(a) and sialyl-Lewis(x) antigens in colorectal adenocarcinoma. Histopathology. 2002;40(5):440–449. doi:10.1046/j.1365-2559.2002.01389.x.
  • Khanh DT, Mekata E, Mukaisho K, Sugihara H, Shimizu T, Shiomi H, Murata S, Naka S, Yamamoto H, Endo Y, et al. Transmembrane mucin MUC1 overexpression and its association with CD10+ myeloid cells, transforming growth factor-β1 expression, and tumor budding grade in colorectal cancer. Cancer Sci. 2013;104(7):958–964. doi:10.1111/cas.12170.
  • Lillehoj EP, Lu W, Kiser T, Goldblum SE, Kim KC. MUC1 inhibits cell proliferation by a beta-catenin-dependent mechanism. Biochim Biophys Acta. 2007;1773(7):1028–1038. doi:10.1016/j.bbamcr.2007.04.009.
  • Díaz Del Arco C, Garré P, Molina Roldán E, Lorca V, Cerón Nieto MÁ, Fernández Aceñero MJ. MUC1 expression in colorectal carcinoma: clinicopathological correlation and prognostic significance. Rev Espanola Patol Publicacion Of Soc Espanola Anat Patol Soc Espanola Citol. 2018;51(4):204–209. doi:10.1016/j.patol.2018.03.002.
  • Betge J, Schneider NI, Harbaum L, Pollheimer MJ, Lindtner RA, Kornprat P, Ebert MP, Langner C. MUC1, MUC2, MUC5AC, and MUC6 in colorectal cancer: expression profiles and clinical significance. Virchows Arch Int J Pathol. 2016;469(3):255–265. doi:10.1007/s00428-016-1970-5.
  • Butts C, Murray RN, Smith CJ, Ellis PM, Jasas K, Maksymiuk A, Goss G, Ely G, Beier F, Soulières D. A multicenter open-label study to assess the safety of a new formulation of BLP25 liposome vaccine in patients with unresectable stage III non-small-cell lung cancer. Clin Lung Cancer. 2010;11(6):391–395. doi:10.3816/CLC.2010.n.101.
  • Butts C, Anderson H, Maksymiuk A, Vergidis D, Soulières D, Cormier Y, Davis M, Marshall E, Falk M, Goss G. Long-term safety of BLP25 liposome vaccine (L-BLP25) in patients (pts) with stage IIIB/IV non-small cell lung cancer (NSCLC). J Clin Oncol. 2009;27(15_suppl):3055. doi:10.1200/jco.2009.27.15_suppl.3055.
  • Cunningham D, Salazar R, Sobrero A, Ducreux MP, Van Cutsem E, Scheithauer W, Tournigand C, Molnar V, Starke M, Baumann M, et al. LBA33Lefitolimod vs standard of care (SOC) for patients with metastatic colorectal cancer (mCRC) responding to first-line standard treatment: results from the randomized phase III IMPALA trial. Ann Oncol. 2019;30(Supplement_5):v868–v869. doi:10.1093/annonc/mdz394.022.
  • Grothey A, Tabernero J, Arnold D, De Gramont A, Ducreux MP, O’Dwyer PJ, Van Cutsem E, Bosanac I, Srock S, Mancao C, et al. LBA19Fluoropyrimidine (FP) + bevacizumab (BEV) + atezolizumab vs FP/BEV in BRAFwt metastatic colorectal cancer (mCRC): findings from Cohort 2 of MODUL – a multicentre, randomized trial of biomarker-driven maintenance treatment following first-line induction therapy. Ann Oncol. 2018;29(suppl_8): doi:10.1093/annonc/mdy424.020