Top

Current Colorectal Cancer Reports

Published in:

01-06-2017 | Personalized Medicine in Colorectal Cancer (D Cunningham and EC Smyth, Section Editors)

Personalizing Maintenance Therapy in Metastatic Colorectal Cancer

Authors: Julia Quidde, Alexander Stein

Published in: Current Colorectal Cancer Reports | Issue 3/2017

Abstract

Purpose of Review

Current systemic management of MCRC should include periods of intensive and less intensive treatment or even complete stop. Different systemic post-induction strategies have been evaluated in many trials. The aim of this article is to review the available data on maintenance strategies in MCRC and potential options to personalize choice of the respective strategy.

Recent Findings

Despite the large variability of clinical trials conducted in this setting, it can be concluded that intermittent chemotherapy does not seem to be inferior to continuous chemotherapy if at least 3 months of intensive induction treatment is applied, and active maintenance seem to be superior to complete stop after at least 3 months of induction treatment in terms of PFS and may add some benefit in terms of OS. The choice of the respective maintenance strategy may be personalized taking into account disease and patient characteristic, choice of induction treatment and response, treatment tolerability and quality of life.

Summary

Patients with metastatic colorectal cancer and no options of secondary resection or local ablation should be considered for a personalized maintenance approach.

Global Burden of Disease Cancer C, Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, et al. The global burden of cancer 2013. JAMA oncology. 2015;1(4):505–27. doi:10.1001/jamaoncol.2015.0735.CrossRef

Malvezzi M, Carioli G, Bertuccio P, Rosso T, Boffetta P, Levi F, et al. European cancer mortality predictions for the year 2016 with focus on leukaemias. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2016;27(4):725–31. doi:10.1093/annonc/mdw022.CrossRef

Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin. 2014;64(2):104–17. doi:10.3322/caac.21220.CrossRefPubMed

• Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386–422. doi:10.1093/annonc/mdw235. The ESMO consensus guidelines have been developed based on the current available evidence to provide a series of expert recommendations to assist in the treatment and management of patients with metastatic colorectal cancer in this rapidly evolving treatment setting. CrossRefPubMed

Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015; doi:10.1016/S1470-2045(15)00122-9.

Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369(11):1023–34. doi:10.1056/NEJMoa1305275.CrossRefPubMed

Van Cutsem E, Lenz HJ, Kohne CH, Heinemann V, Tejpar S, Melezinek I, et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol. 2015;33(7):692–700. doi:10.1200/JCO.2014.59.4812.CrossRefPubMed

Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065–75. doi:10.1016/S1470-2045(14)70330-4.CrossRefPubMed

Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26(12):2013–9.CrossRefPubMed

10.

Maughan TS, James RD, Kerr DJ, Ledermann JA, Seymour MT, Topham C, et al. Comparison of intermittent and continuous palliative chemotherapy for advanced colorectal cancer: a multicentre randomised trial. Lancet. 2003;361(9356):457–64.CrossRefPubMed

11.

Adams RA, Meade AM, Seymour MT, Wilson RH, Madi A, Fisher D, et al. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. The Lancet Oncology. 2011;12(7):642–53. doi:10.1016/S1470-2045(11)70102-4.CrossRefPubMedPubMedCentral

12.

Tournigand C, Cervantes A, Figer A, Lledo G, Flesch M, Buyse M, et al. OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer—a GERCOR study. J Clin Oncol. 2006;24(3):394–400. doi:10.1200/JCO.2005.03.0106.CrossRefPubMed

13.

Labianca R, Sobrero A, Isa L, Cortesi E, Barni S, Nicolella D, et al. Intermittent versus continuous chemotherapy in advanced colorectal cancer: a randomised ‘GISCAD’ trial. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2011;22(5):1236–42. doi:10.1093/annonc/mdq580.CrossRef

14.

Diaz-Rubio E, Gomez-Espana A, Massuti B, Sastre J, Abad A, Valladares M, et al. First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study. Oncologist. 2012;17(1):15–25. doi:10.1634/theoncologist.2011-0249.CrossRefPubMedPubMedCentral

15.

Yalcin S, Uslu R, Dane F, Yilmaz U, Zengin N, Buyukunal E, et al. Bevacizumab + capecitabine as maintenance therapy after initial bevacizumab + XELOX treatment in previously untreated patients with metastatic colorectal cancer: phase III ‘Stop and Go’ study results—a Turkish oncology group trial. Oncology. 2013;85(6):328–35. doi:10.1159/000355914.CrossRefPubMed

16.

Hochster HS, Grothey A, Hart L, Rowland K, Ansari R, Alberts S, et al. Improved time to treatment failure with an intermittent oxaliplatin strategy: results of CONcePT. Ann Oncol. 2014;25(6):1172–8. doi:10.1093/annonc/mdu107.CrossRefPubMedPubMedCentral

17.

Pfeiffer P, Sorbye H, Qvortrup C, Karlberg M, Kersten C, Vistisen K, et al. Maintenance therapy with cetuximab every second week in the first-line treatment of metastatic colorectal cancer: the NORDIC-7.5 study by the nordic colorectal cancer biomodulation group. Clin Colorectal Cancer. 2015;14(3):170–6. doi:10.1016/j.clcc.2015.03.002.CrossRefPubMed

18.

Tveit KM, Guren T, Glimelius B, Pfeiffer P, Sorbye H, Pyrhonen S, et al. Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol. 2012;30(15):1755–62. doi:10.1200/JCO.2011.38.0915.CrossRefPubMed

19.

Chibaudel B, Maindrault-Goebel F, Lledo G, Mineur L, Andre T, Bennamoun M, et al. Can chemotherapy be discontinued in unresectable metastatic colorectal cancer? The GERCOR OPTIMOX2 study. J Clin Oncol. 2009;27(34):5727–33. doi:10.1200/JCO.2009.23.4344.CrossRefPubMed

20.

• Simkens LH, van Tinteren H, May A, Ten Tije AJ, Creemers GJ, Loosveld OJ, et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch colorectal cancer group. Lancet. 2015;385(9980):1843–52. doi:10.1016/S0140-6736(14)62004-3. The CAIRO3 study was designed to determine the efficacy of maintenance treatment with capecitabine plus bevacizumab versus observation. It showed that maintenance treatment with capecitabine plus bevacizumab after six cycles of CAPOX-B in patients with metastatic colorectal cancer prolongs progression free survival and does not compromise quality of life. CrossRefPubMed

21.

Koeberle D, Betticher DC, von Moos R, Dietrich D, Brauchli P, Baertschi D, et al. Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06). Ann Oncol. 2015;26(4):709–14. doi:10.1093/annonc/mdv011.CrossRefPubMed

22.

• Hegewisch-Becker S, Graeven U, Lerchenmuller CA, Killing B, Depenbusch R, Steffens CC, et al. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol. 2015; doi:10.1016/S1470-2045(15)00042-X. Randomized trial investigating different maintenance strategies after first-line induction treatment with fluoropyrimidine, oxaliplatin and bevacizumab. An active maintenance treatment, either with a fluoropyrimidine plus bevacizumab or with bevacizumab alone, is associated with a longer progression free survival, but choice of maintenance or post-induction strategy does not affect overall survival.

23.

Stein A, Schwenke C, Folprecht G, Arnold D. Effect of application and intensity of Bevacizumab-based maintenance after induction chemotherapy with Bevacizumab for metastatic colorectal cancer: a meta-analysis. Clin Colorectal Cancer. 2016;15(2):e29–39. doi:10.1016/j.clcc.2015.12.005.CrossRefPubMed

24.

Wasan H, Meade AM, Adams R, Wilson R, Pugh C, Fisher D, et al. Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial. Lancet Oncol. 2014;15(6):631–9. doi:10.1016/S1470-2045(14)70106-8.CrossRefPubMedPubMedCentral

25.

Tournigand C, Chibaudel B, Samson B, Scheithauer W, Vernerey D, Mesange P, et al. Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2015;16(15):1493–505. doi:10.1016/S1470-2045(15)00216-8.CrossRefPubMed

26.

Johnsson A, Hagman H, Frodin JE, Berglund A, Keldsen N, Fernebro E, et al. A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer: the Nordic ACT trial. Ann Oncol. 2013;24(9):2335–41. doi:10.1093/annonc/mdt236.CrossRefPubMed

27.

Goey KKH, Elias SG, Van Tinteren H. Predictive value of KRAS mutation status in metastatic colorectal cancer (mCRC) patients treated with capecitabine and bevacizumab (CAP-B) maintenance treatment vs observation in the phase III CAIRO3 study. J Clin Oncol. 2016;34(suppl):abstr 3525.

28.

• Quidde J, Hegewisch-Becker S, Graeven U, Lerchenmuller CA, Killing B, Depenbusch R, et al. Quality of life assessment in patients with metastatic colorectal cancer receiving maintenance therapy after first-line induction treatment: a preplanned analysis of the phase III AIO KRK 0207 trial. Ann Oncol. 2016;27(12):2203–10. doi:10.1093/annonc/mdw425. This was one of the first studies analysing quality of life during maintenance treatment. The study showed that continuation of an active maintenance treatment with fluoropyrimidine and bevacizumab after induction treatment was neither associated with a detrimental effect on health related quality of life when compared to bevacizumab alone or no active treatment. CrossRefPubMed

Title: Personalizing Maintenance Therapy in Metastatic Colorectal Cancer
Authors: Julia Quidde
Alexander Stein
Publication date: 01-06-2017
Publisher: Springer US
Published in: Current Colorectal Cancer Reports / Issue 3/2017
Print ISSN: 1556-3790
Electronic ISSN: 1556-3804
DOI: https://doi.org/10.1007/s11888-017-0365-6

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

Other articles of this Issue 3/2017

Current Views on the Interval Between Neoadjuvant Chemoradiation and Surgery for Rectal Cancer

Anti-EGFR and Anti-VEGF Agents in First-Line Therapy for Advanced Colorectal Cancer

Using 3D Organoid Cultures to Model Intestinal Physiology and Colorectal Cancer

Current Trends in the Use of Bowel Preparation for Colorectal Surgery

Radiotherapy for the Primary Tumor in Patients with Metastatic Rectal Cancer

Radiation Therapy for Colorectal Liver Metastases

Keynote webinar | Spotlight on antibody–drug conjugates in cancer