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Journal of Cancer Research and Clinical Oncology

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06.11.2019 | Original Article – Clinical Oncology

Clinical impact of first-line bevacizumab plus chemotherapy in metastatic colorectal cancer of mucinous histology: a multicenter, retrospective analysis on 685 patients

verfasst von: Vincenzo Catalano, Francesca Bergamo, Chiara Cremolini, Bruno Vincenzi, Francesca Negri, Paolo Giordani, Paolo Alessandroni, Rossana Intini, Silvia Stragliotto, Daniele Rossini, Beatrice Borelli, Daniele Santini, Donatella Sarti, Marco B. L. Rocchi, Sara Lonardi, Alfredo Falcone, Vittorina Zagonel, Rodolfo Mattioli, Francesco Graziano

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2020

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Abstract

Purpose

In metastatic colorectal cancer (MCRC), mucinous histology has been associated with poor response rate and prognosis. We investigated whether bevacizumab combined with different chemotherapy regimens may have an impact on clinical outcomes of MCRC patients with mucinous histology.

Methods

685 MCRC patients were classified in mucinous adenocarcinoma (MC) and non-mucinous adenocarcinoma (NMC) and were treated with first-line bevacizumab plus fluoropyrimidine (FP)-based, oxaliplatin (OXA)-based, irinotecan (IRI)-based, or FOLFOXIRI.

Results

Ninety-four (13.7%) patients had MC. With a median follow-up of 50 months, MC patients had a median overall survival (OS) of 28.2 months compared with 27.7 months for the NMC group [hazard ratio (HR) = 0.92; 95% confidence interval (CI) 0.70–1.19, P = 0.530]. The overall response rates for MC and NMC were 41.5% (95% CI 31.5–51.4) and 62.4% (95% CI 58.4–66.3), respectively (Chi-square test, P <0.003). After correcting for significant prognostic factors by multivariate Cox regression analysis, age, resection of the primary tumour, and number of metastatic sites were found to be associated with poorer OS, but not mucinous histology.

Conclusion

Compared with NMC, MCRC patients with mucinous histology treated with bevacizumab plus chemotherapy had comparable OS despite lower overall response rate.

Catalano V, Loupakis F, Graziano F, Torresi U, Bisonni R, Mari D et al (2009) Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy. Br J Cancer 100:881–887CrossRef

Consorti F, Lorenzotti A, Midiri G, Di Paola M (2000) Prognostic significance of mucinous carcinoma of colon and rectum: a prospective case–control study. J Surg Oncol 73:70–74CrossRef

Del Rio M, Mollevi C, Bibeau F, Vie N, Selves J, Emile JF, Roger P, Gongora C, Robert J, Tubiana-Mathieu N, Ychou M, Martineau P (2017) Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies. Eur J Cancer 76:68–75CrossRef

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRef

Ferrara N, Hillan KJ, Gerber HP, Novotny W (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3:391–400CrossRef

Glasgow SC, Yu J, Carvalho LP, Shannon WD, Fleshman JW, McLeod HL (2005) Unfavourable expression of pharmacologic markers in mucinous colorectal cancer. Br J Cancer 92:259–264CrossRef

Green JB, Timmcke AE, Mitchell WT, Hicks TC, Gathright JB Jr, Ray JE (1993) Mucinous carcinoma—just another colon cancer? Dis Colon Rectum 36:49–54CrossRef

Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C et al (2015) The consensus molecular subtypes of colorectal cancer. Nat Med 21:350–356CrossRef

Hamilton SR, Bosman FT, Boffetta P et al (2010) Carcinoma of the colon and rectum. In: Bosman FT, Carneiro F, Hruban RH, Theise ND (eds) WHO Classification of tumours of the digestive system, 4th edn. International Agency for Research on Cancer Press, Lyon, pp 134–146

Hugen N, Simons M, Halilović A, van der Post RS, Bogers AJ, Marijnissen-van Zanten MA, de Wilt JH, Nagtegaal ID (2014) The molecular background of mucinous carcinoma beyond MUC2. J Pathol Clin Res 1:3–17CrossRef

Hugen N, Brown G, Glynne-Jones R, de Wilt JH, Nagtegaal ID (2016) Advances in the care of patients with mucinous colorectal cancer. Nat Rev Clin Oncol 13:361–369CrossRef

Hyngstrom JR, Hu CY, Xing Y, You YN, Feig BW, Skibber JM, Rodriguez-Bigas MA, Cormier JN, Chang GJ (2012) Clinicopathology and outcomes for mucinous and signet ring colorectal adenocarcinoma: analysis from the National Cancer Data Base. Ann Surg Oncol 19:2814–2821CrossRef

Jung YS, Wang W, Jun S, Zhang J, Srivastava M, Kim MJ, Lien EM, Shang J, Chen J, McCrea PD, Zhang S, Park JI (2018) Deregulation of CRAD-controlled cytoskeleton initiates mucinous colorectal cancer via β-catenin. Nat Cell Biol 20:1303–1314CrossRef

Kanemitsu Y, Kato T, Hirai T, Yasui K, Morimoto T, Shimizu Y, Kodera Y, Yamamura Y (2003) Survival after curative resection for mucinous adenocarcinoma of the colorectum. Dis Colon Rectum 46:160–167CrossRef

Kang H, O’Connell JB, Maggard MA, Sack J, Ko CY (2005) A 10-year outcomes evaluation of mucinous and signet-ring cell carcinoma of the colon and rectum. Dis Colon Rectum 48:1161–1168CrossRef

Khan M, Loree JM, Advani SM, Ning J, Li W, Pereira AAL et al (2018) Prognostic Implications of mucinous differentiation in metastatic colorectal carcinoma can be explained by distinct molecular and clinicopathologic characteristics. Clin Colorectal Cancer 17:e699–e709CrossRef

Komatsu M, Jepson S, Arango ME, Carothers Carraway CA, Carraway KL (2001) Muc4/sialomucin complex, an intramembrane modulator of ErbB2/HER2/Neu, potentiates primary tumour growth and suppresses apoptosis in a xenotransplanted tumour. Oncogene 20:461–470CrossRef

Koopman M, Antonini NF, Douma J, Wals J, Honkoop AH, Erdkamp FL et al (2007) Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet 370:135–142CrossRef

Maisano R, Azzarello D, Maisano M, Mafodda A, Bottari M, Egitto G, Nardi M (2012) Mucinous histology of colon cancer predicts poor outcomes with FOLFOX regimen in metastatic colon cancer. J Chemother 24:212–216CrossRef

Marisa L, de Reyniès A, Duval A, Selves J, Gaub MP, Vescovo L et al (2013) Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 10:e1001453CrossRef

Mekenkamp LJ, Heesterbeek KJ, Koopman M, Tol J, Teerenstra S, Venderbosch S, Punt CJ, Nagtegaal ID (2012) Mucinous adenocarcinomas: poor prognosis in metastatic colorectal cancer. Eur J Cancer 48:501–509CrossRef

Mooi JK, Wirapati P, Asher R, Lee CK, Savas P, Price TJ et al (2018) The prognostic impact of consensus molecular subtypes (CMS) and its predictive effects for bevacizumab benefit in metastatic colorectal cancer: molecular analysis of the AGITG MAX clinical trial. Ann Oncol 29:2240–2246CrossRef

Negri FV, Wotherspoon A, Cunningham D, Norman AR, Chong G, Ross PJ (2005) Mucinous histology predicts for reduced fluorouracil responsiveness and survival in advanced colorectal cancer. Ann Oncol 16:1305–1310CrossRef

Okita A, Takahashi S, Ouchi K, Inoue M, Watanabe M, Endo M, Honda H, Yamada Y, Ishioka C (2018) Consensus molecular subtypes classification of colorectal cancer as a predictive factor for chemotherapeutic efficacy against metastatic colorectal cancer. Oncotarget 9:18698–18711PubMedPubMedCentral

Sadanandam A, Lyssiotis CA, Homicsko K, Collisson EA, Gibb WJ, Wullschleger S et al (2013) A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 19:619–625CrossRef

Smeets D, Miller IS, O’Connor DP, Das S, Moran B, Boeckx B et al (2018) Copy number load predicts outcome of metastatic colorectal cancer patients receiving bevacizumab combination therapy. Nat Commun 9:4112CrossRef

Stylianopoulos T, Jain RK (2013) Combining two strategies to improve perfusion and drug delivery in solid tumors. Proc Natl Acad Sci USA 110:18632–18637CrossRef

Tol J, Koopman M, Cats A, Rodenburg CJ, Creemers GJ, Schrama JG et al (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360:563–572CrossRef

Verhulst J, Ferdinande L, Demetter P, Ceelen W (2012) Mucinous subtype as prognostic factor in colorectal cancer: a systematic review and metaanalysis. J Clin Pathol 65:381–388CrossRef

Weiss AA, Babyatsky MW, Ogata S, Chen A, Itzkowitz SH (1996) Expression of MUC2 and MUC3 mRNA in human normal, malignant, and inflammatory intestinal tissues. J Histochem Cytochem 44:1161–1166CrossRef

Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT et al (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10:145–147CrossRef

Titel: Clinical impact of first-line bevacizumab plus chemotherapy in metastatic colorectal cancer of mucinous histology: a multicenter, retrospective analysis on 685 patients
verfasst von: Vincenzo Catalano
Francesca Bergamo
Chiara Cremolini
Bruno Vincenzi
Francesca Negri
Paolo Giordani
Paolo Alessandroni
Rossana Intini
Silvia Stragliotto
Daniele Rossini
Beatrice Borelli
Daniele Santini
Donatella Sarti
Marco B. L. Rocchi
Sara Lonardi
Alfredo Falcone
Vittorina Zagonel
Rodolfo Mattioli
Francesco Graziano
Publikationsdatum: 06.11.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2020
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-03077-w

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Clinical impact of first-line bevacizumab plus chemotherapy in metastatic colorectal cancer of mucinous histology: a multicenter, retrospective analysis on 685 patients