ONCOGRAM: study protocol for the evaluation of therapeutic response and survival of metastatic colorectal cancer patients treated according to the guidelines of a chemosensitivity assay, the Oncogramme®

Muriel Mathonnet, Mathieu Vanderstraete, Christophe Bounaix Morand du Puch, Stéphanie Giraud, Christophe Lautrette, Mehdi Ouaissi, Nicolas Tabchouri, Abdelkader Taïbi, Renaud Martin, Isabelle Herafa, Achille Tchalla, Niki Christou, ONCOGRAM trial investigators, B Marin, S Bouvier, S Durand-Fontanier, A Fabre, D Valleix, T Rivaille, F Fredon, S Derbal, P Carrier, R Daloko Lonfo, R Legros, S Lavau-Denes, V Lebrun-Ly, F Thuillier, P Engel, A Chaunavel, M Pradel, D Pezet, A Dubois, C Pétorin, O Antomarchi, A Aboukassem, A Vimal-Baguet, B Gillet, B Mathieu, J Joubert-Zakeyh, S Evrard, Y Becouarn, D Béchade, M Fonk, G Desolneux, N Dauriat, M Agbo, M Louty, F Borie, S Lyubimova, V Phoutthasang, B Brunaud-Gagniard, Y Benadjaoud, N Rolland, L Letournoux, P Roger, L Chen, Z Amadou, C Christopoulous, G Nakahl, Y Souliman, M N Cirt, D Ducoux, P A Boisseau, P Pardies, L Mesturoux, L Vayre, A Abdeh, F Teboul, R Landraud, M Ouaissi, E Salamé, N Tabchouri, T Lecomte, G Proutheau, S Guyetant, D Tougeron, A de Singly, A Ferru, R El Fadel, T Courvoisier, A Junca, E Frouin, L Rouleau, S Rafaert, A Rocher, J-M Regimbeau, C Sabbagh, E Dumange, E Chive, D Lignier, N Siembida, B Chauffert, V Hautefeuille, D Chatelain, E Rivkine, Muriel Mathonnet, Mathieu Vanderstraete, Christophe Bounaix Morand du Puch, Stéphanie Giraud, Christophe Lautrette, Mehdi Ouaissi, Nicolas Tabchouri, Abdelkader Taïbi, Renaud Martin, Isabelle Herafa, Achille Tchalla, Niki Christou, ONCOGRAM trial investigators, B Marin, S Bouvier, S Durand-Fontanier, A Fabre, D Valleix, T Rivaille, F Fredon, S Derbal, P Carrier, R Daloko Lonfo, R Legros, S Lavau-Denes, V Lebrun-Ly, F Thuillier, P Engel, A Chaunavel, M Pradel, D Pezet, A Dubois, C Pétorin, O Antomarchi, A Aboukassem, A Vimal-Baguet, B Gillet, B Mathieu, J Joubert-Zakeyh, S Evrard, Y Becouarn, D Béchade, M Fonk, G Desolneux, N Dauriat, M Agbo, M Louty, F Borie, S Lyubimova, V Phoutthasang, B Brunaud-Gagniard, Y Benadjaoud, N Rolland, L Letournoux, P Roger, L Chen, Z Amadou, C Christopoulous, G Nakahl, Y Souliman, M N Cirt, D Ducoux, P A Boisseau, P Pardies, L Mesturoux, L Vayre, A Abdeh, F Teboul, R Landraud, M Ouaissi, E Salamé, N Tabchouri, T Lecomte, G Proutheau, S Guyetant, D Tougeron, A de Singly, A Ferru, R El Fadel, T Courvoisier, A Junca, E Frouin, L Rouleau, S Rafaert, A Rocher, J-M Regimbeau, C Sabbagh, E Dumange, E Chive, D Lignier, N Siembida, B Chauffert, V Hautefeuille, D Chatelain, E Rivkine

Abstract

Background: Colorectal cancer is a major public concern, being the second deadliest cancer in the world. Whereas survival is high for localized forms, metastatic colorectal cancer has showed poor prognosis, with a 5-year survival barely surpassing 11%. Conventional chemotherapies against this disease proved their efficiency and remain essential in first-line treatment. However, the large number of authorized protocols complexifies treatment decision. In common practice, such decision is made on an empirical basis, by assessing benefits and risks for the patient. In other words, there is currently no efficient means of predicting the efficacy of any chemotherapy protocol for metastatic colorectal cancer.

Methods/design: The use of a chemosensitivity assay, the Oncogramme®, should help clinicians administer the best chemotherapy regimen to their patients. We hypothesize it would ultimately improve their survival. In this multicentred, prospective trial (ONCOGRAM), eligible patients with metastatic colorectal cancer are randomized to determine whether they will receive an Oncogramme®. For clinicians whose patients benefited from the assay (arm A), results are used as a decision support tool. Patients not undergoing the Oncogramme® procedure are treated according to current practice, without the assistance of the assay (arm B). Primary outcome is 1-year progression-free survival. Secondary outcomes include response rates, as well as 6-month and 1-year survival rates.

Discussion: This study aims at investigating the clinical utility of the Oncogramme® as a decision support tool for the treatment of patients with metastatic colorectal cancer. If the Oncogramme® positively influenced patient overall survival and/or progression-free survival, it would be of great value for clinicians to implement this assay within the current landscape of personalized medicine tools, which include genomics and biomarker assays.

Trial registration: ClinicalTrials.gov identifier NCT03133273 . Registered on April 28, 2017.

Keywords: CSRA; Chemosensitivity; Colorectal cancer; Functional assay; Metastatic; ONCOGRAM; Oncogramme®; Personalized medicine.

Conflict of interest statement

CL and SG are cofounders of Oncomedics SAS and have equity positions in the company. MV and CMBP are employees of Oncomedics SAS. MM, NC, MO, NT, AT, RM, IH and AT as well as the ONCOGRAM trial investigators declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
ONCOGRAM diagram for confirmed mCRC samples. When mCRC is already histologically diagnosed, inclusion and randomization occur before performing the Oncogramme®. Oncomedics only receives samples and realizes the assays for patients already randomized in the Oncogramme® arm
Fig. 2
Fig. 2
ONCOGRAM diagram for suspected mCRC samples. Oncomedics receives and starts the Oncogramme® procedure on all samples not histologically qualified yet. Randomization occurs if the sample is confirmed as mCRC. Realization of the Oncogramme® is pursued only if the patient is randomized in the Oncogramme® arm. In all other cases, the sample is eliminated

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi: 10.3322/caac.21492.
    1. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683–691. doi: 10.1136/gutjnl-2015-310912.
    1. Marley AR, Nan H. Epidemiology of colorectal cancer. Int J Mol Epidemiol Genet. 2016;7(3):105–114.
    1. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383(9927):1490–1502. doi: 10.1016/S0140-6736(13)61649-9.
    1. Lee JJ, Chu E. An update on treatment advances for the first-line therapy of metastatic colorectal cancer. Cancer J. 2007;13(5):276–281. doi: 10.1097/PPO.0b013e3181570062.
    1. Holch J, Stintzing S, Heinemann V. Treatment of metastatic colorectal cancer: Standard of care and future perspectives. Visc Med. 2016;32(3):178–183. doi: 10.1159/000446052.
    1. Ikoma N, Raghav K, Chang G. An Update on Randomized Clinical Trials in Metastatic Colorectal Carcinoma. Surg Oncol Clin N Am. 2017;26(4):667–687. doi: 10.1016/j.soc.2017.05.007.
    1. Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, Goldberg MV, Cao ZA, Ledeine JM, Maglinte GA, Kopetz S, André T. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18(9):1182–1191. doi: 10.1016/S1470-2045(17)30422-9.
    1. Marcus L, Lemery SJ, Keegan P, Pazdur R. FDA approval summary: Pembrolizumab for the treatment of microsatellite instability-high solid tumors. Clin Cancer Res. 2019;25(13):3753–3758. doi: 10.1158/1078-0432.CCR-18-4070.
    1. Neugut AI, Lin A, Raab GT, Hillyer GC, Keller D, O’Neil DS, Accordino MK, Kiran RP, Wright J, Hershman DL. FOLFOX and FOLFIRI Use in Stage IV Colon Cancer: Analysis of SEER-Medicare Data. Clin Colorectal Cancer. 2019;18(2):133–140. doi: 10.1016/j.clcc.2019.01.005.
    1. Ychou M, Rivoire M, Thezenas S, Quenet F, Delpero JR, Rebischung C, et al. A randomized phase II trial of three intensified chemotherapy regimens in first-line treatment of colorectal cancer patients with initially unresectable or not optimally resectable liver metastases. the METHEP trial. Ann Surg Oncol. 2013. 10.1245/s10434-013-3217-x.
    1. Deyme L, Barbolosi D, Gattacceca F. Population pharmacokinetics of FOLFIRINOX: a review of studies and parameters. Cancer Chemother Pharmacol. 2019;83(1):27–42. doi: 10.1007/s00280-018-3722-5.
    1. Blom K, Nygren P, Larsson R, Andersson CR. Predictive Value of Ex Vivo Chemosensitivity Assays for Individualized Cancer Chemotherapy: A Meta-Analysis. SLAS Technol. 2017;22(3):306–314. doi: 10.1177/2472630316686297.
    1. Burstein HJ, Mangu PB, Somerfield MR, Schrag D, Samson D, Holt L, Zelman D, Ajani JA, American Society of Clinical Oncology American Society of Clinical Oncology clinical practice guideline update on the Use of chemotherapy sensitivity and resistance assays. J Clin Oncol. 2011;29(24):3328–3330. doi: 10.1200/JCO.2011.36.0354.
    1. Hur H, Kim NK, Kim HG, Min BS, Lee KY, Shin SJ, Cheon JH, Choi SH. Adenosine triphosphate-based chemotherapy response assay-guided chemotherapy in unresectable colorectal liver metastasis. Br J Cancer. 2012;106(1):53–60. doi: 10.1038/bjc.2011.469.
    1. Cree IA, Kurbacher CM, Lamont A, Hindley AC, Love S, Cree IA, et al. A prospective randomized controlled trial of tumour chemosensitivity assay directed chemotherapy versus physician’s choice in patients with recurrent platinum-resistant ovarian cancer. Anticancer Drugs. 2007;18(9):1093–1101. doi: 10.1097/CAD.0b013e3281de727e.
    1. Loum E, Giraud S, Bessette B, Battu S, Mathonnet M, Lautrette C. Oncogramme, a new individualized tumor response testing method: Application to colon cancer. Cytotechnology. 2010;62(5):381–388. doi: 10.1007/s10616-010-9298-5.
    1. Giraud S, Loum E, Bessette B, Fermeaux V, Lautrette C. Oncogramme, a new promising method for individualized breast tumour response testing for cancer treatment. Anticancer Res. 2011;31(1):139–145.
    1. Giraud S. Oncogramme, an Adapted Method for Individualized Tumour Response Testing of Ovary Cancer Treatments. J Cancer Res Ther Oncol. 2014. 10.17303/jcrto.2014.2.303.
    1. Bounaix Morand du Puch C, Giraud S, Lautrette C, Nouaille M, Labrunie A, Luce S, et al. Chemotherapy outcome predictive effectiveness by the Oncogramme: Pilot trial on stage-IV colorectal cancer. J Transl Med. 2016. 10.1186/s12967-016-0765-4.
    1. Yoon YS, Kim JC. Recent applications of chemosensitivity tests for colorectal cancer treatment. World J Gastroenterol. 2014;20(44):16398–16408. doi: 10.3748/wjg.v20.i44.16398.
    1. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009. 10.1016/j.ejca.2008.10.026.
    1. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomized trials. BMJ. 2010;340(mar23 1):c332. doi: 10.1136/bmj.c332.
    1. Giraud S, Bounaix Morand du Puch C, Fermeaux V, Guillaudeau A, Lautrette C. Oncogramme responses of breast tumour cells treated with herceptin correlate with HER2/C-ERB B2 pathological status. Anticancer Res. 2012;32:1323–1325.

Source: PubMed

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