Skip to main content
Top
Published in: Clinical and Translational Oncology 11/2019

01-11-2019 | Panitumumab | Research Article

Skeletal muscle loss during anti-EGFR combined chemotherapy regimens predicts poor prognosis in patients with RAS wild metastatic colorectal cancer

Authors: O. Köstek, N. C. Demircan, A. Gökyer, A. Küçükarda, B. S. Sunal, M. B. Hacıoğlu, H. Eslame, S. Solak, E. Yılmaz, S. Uzunoğlu, N. Tunçbilek, İ. Çiçin, B. Erdoğan

Published in: Clinical and Translational Oncology | Issue 11/2019

Login to get access

Abstract

Purpose

We aimed to assess whether anti-EGFR combined chemotherapy regimens are related with loss of skeletal muscle mass and to compare cetuximab and panitumumab therapies in the aspect of skeletal muscle area change as well as to assess whether skeletal muscle mass loss has prognostic significance in the RAS wild mCRC patients.

Materials and methods

A total of 56 patients (30 patients in cetuximab arm and 26 patients in panitumumab) who had computed tomography images were retrospectively evaluated at the diagnosis and follow up during the treatment period before progression.

Results

During treatment period 24 patients (42.8%) had muscle loss. Of these, 7 (29.2%) patients were treated at first-line and 17 (70.8%) patients were treated at second-line setting. There was no significant difference in the aspect of skeletal muscle loss among cetuximab and panitumumab combined treatment regimens. Median PFS was 9.1 (8.6–9.6) months in muscle loss group and 13.9 (7.2–20.6) months in muscle stable group (p = 0.001). Median OS was 23.4 (95% CI 15.8–31.0) months in muscle stable group and 19.1 (95% CI 17.0–21.3) months in muscle loss group (p = 0.57) at first-line setting. For second-line, median OS was 21.2 (14.7–27.7) months in muscle stable group and 14.4 (6.0-22.4) months in muscle loss group (p = 0.003).

Conclusions

Decrease in skeletal muscle mass before progression on CT imaging is an independent indicator for shorter PFS value in RAS WT mCRC patients who received anti-EGFR combined chemotherapy regimens at both the first and second-line settings. Beside that shorter overall survival values also were significantly seen in patients who had muscle loss during anti-EGFR therapy in the second-line setting.
Literature
1.
go back to reference Noone A, Howlader N, Krapcho M et al. SEER Cancer Statistics Review, 1975-2015, based on November 2017 SEER data submission, posted to the SEER web site, April 2018. Bethesda, MD: National Cancer Institute; 2018. In. 2018. Noone A, Howlader N, Krapcho M et al. SEER Cancer Statistics Review, 1975-2015, based on November 2017 SEER data submission, posted to the SEER web site, April 2018. Bethesda, MD: National Cancer Institute; 2018. In. 2018.
2.
go back to reference Herbst RS, Shin DM. Monoclonal antibodies to target epidermal growth factor receptor-positive tumors: a new paradigm for cancer therapy. Cancer. 2002;94:1593–611.CrossRef Herbst RS, Shin DM. Monoclonal antibodies to target epidermal growth factor receptor-positive tumors: a new paradigm for cancer therapy. Cancer. 2002;94:1593–611.CrossRef
3.
go back to reference Ottaiano A, De Stefano A, Capozzi M, et al. First Biologic Drug in the Treatment of RAS Wild-Type Metastatic Colorectal Cancer: Anti-EGFR or Bevacizumab? Results From a Meta-Analysis. Front Pharmacol. 2018;9:441.PubMed Ottaiano A, De Stefano A, Capozzi M, et al. First Biologic Drug in the Treatment of RAS Wild-Type Metastatic Colorectal Cancer: Anti-EGFR or Bevacizumab? Results From a Meta-Analysis. Front Pharmacol. 2018;9:441.PubMed
4.
go back to reference Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17.CrossRef Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17.CrossRef
5.
go back to reference Peeters M, Price TJ, Cervantes A, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28:4706–13.CrossRef Peeters M, Price TJ, Cervantes A, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28:4706–13.CrossRef
6.
go back to reference Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010;28:4697–705.CrossRef Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010;28:4697–705.CrossRef
7.
go back to reference Bokemeyer C, Bondarenko I, Makhson A, et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009;27:663–71.CrossRef Bokemeyer C, Bondarenko I, Makhson A, et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009;27:663–71.CrossRef
8.
go back to reference Fukushima H, Takemura K, Suzuki H, Koga F. Impact of Sarcopenia as a Prognostic Biomarker of Bladder Cancer. 2018; 19. Fukushima H, Takemura K, Suzuki H, Koga F. Impact of Sarcopenia as a Prognostic Biomarker of Bladder Cancer. 2018; 19.
9.
go back to reference Argiles JM, Busquets S, Stemmler B, Lopez-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14:754–62.CrossRef Argiles JM, Busquets S, Stemmler B, Lopez-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14:754–62.CrossRef
10.
go back to reference Antoun S, Baracos VE, Birdsell L, et al. Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma. Ann Oncol. 2010;21:1594–8.CrossRef Antoun S, Baracos VE, Birdsell L, et al. Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma. Ann Oncol. 2010;21:1594–8.CrossRef
11.
go back to reference Mitsiopoulos N, Baumgartner RN, Heymsfield SB, et al. Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol. 1985;1998(85):115–22. Mitsiopoulos N, Baumgartner RN, Heymsfield SB, et al. Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol. 1985;1998(85):115–22.
12.
go back to reference Kurk SA, Peeters PHM, Dorresteijn B, et al. Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients. J Cachexia Sarcopenia Muscle. 2018;9:909–19.CrossRef Kurk SA, Peeters PHM, Dorresteijn B, et al. Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients. J Cachexia Sarcopenia Muscle. 2018;9:909–19.CrossRef
13.
go back to reference Hecht JR, Douillard JY, Schwartzberg L, et al. Extended RAS analysis for anti-epidermal growth factor therapy in patients with metastatic colorectal cancer. Cancer Treat Rev. 2015;41:653–9.CrossRef Hecht JR, Douillard JY, Schwartzberg L, et al. Extended RAS analysis for anti-epidermal growth factor therapy in patients with metastatic colorectal cancer. Cancer Treat Rev. 2015;41:653–9.CrossRef
14.
go back to reference Douillard JY, Siena S, Cassidy J, et al. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014;25:1346–55.CrossRef Douillard JY, Siena S, Cassidy J, et al. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014;25:1346–55.CrossRef
15.
go back to reference Heinemann V, von Weikersthal LF, Decker T, 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;15:1065–75.CrossRef Heinemann V, von Weikersthal LF, Decker T, 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;15:1065–75.CrossRef
16.
go back to reference Ciardiello F, Lenz H-J, Kohne C-H et al. Treatment outcome according to tumor RAS mutation status in CRYSTAL study patients with metastatic colorectal cancer (mCRC) randomized to FOLFIRI with/without cetuximab. In. American Society of Clinical Oncology 2014. Ciardiello F, Lenz H-J, Kohne C-H et al. Treatment outcome according to tumor RAS mutation status in CRYSTAL study patients with metastatic colorectal cancer (mCRC) randomized to FOLFIRI with/without cetuximab. In. American Society of Clinical Oncology 2014.
17.
go back to reference Price TJ, Peeters M, Kim TW, et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014;15:569–79.CrossRef Price TJ, Peeters M, Kim TW, et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014;15:569–79.CrossRef
18.
go back to reference Miyake M, Morizawa Y, Hori S, et al. Clinical impact of postoperative loss in psoas major muscle and nutrition index after radical cystectomy for patients with urothelial carcinoma of the bladder. BMC Cancer. 2017;17:237.CrossRef Miyake M, Morizawa Y, Hori S, et al. Clinical impact of postoperative loss in psoas major muscle and nutrition index after radical cystectomy for patients with urothelial carcinoma of the bladder. BMC Cancer. 2017;17:237.CrossRef
19.
go back to reference Zargar H, Almassi N, Kovac E, et al. Change in Psoas Muscle Volume as a Predictor of Outcomes in Patients Treated with Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer. Bladder Cancer. 2017;3:57–63.CrossRef Zargar H, Almassi N, Kovac E, et al. Change in Psoas Muscle Volume as a Predictor of Outcomes in Patients Treated with Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer. Bladder Cancer. 2017;3:57–63.CrossRef
20.
go back to reference Fukushima H, Kataoka M, Nakanishi Y, et al. Posttherapeutic skeletal muscle mass recovery predicts favorable prognosis in patients with advanced urothelial carcinoma receiving first-line platinum-based chemotherapy. Urol Oncol. 2018;36(156):e159–156.e116. Fukushima H, Kataoka M, Nakanishi Y, et al. Posttherapeutic skeletal muscle mass recovery predicts favorable prognosis in patients with advanced urothelial carcinoma receiving first-line platinum-based chemotherapy. Urol Oncol. 2018;36(156):e159–156.e116.
21.
go back to reference Levolger S, van Vugt JL, de Bruin RW, JN IJ. Systematic review of sarcopenia in patients operated on for gastrointestinal and hepatopancreatobiliary malignancies. Br J Surg 2015; 102: 1448-1458.CrossRef Levolger S, van Vugt JL, de Bruin RW, JN IJ. Systematic review of sarcopenia in patients operated on for gastrointestinal and hepatopancreatobiliary malignancies. Br J Surg 2015; 102: 1448-1458.CrossRef
22.
go back to reference Kamarajah SK, Bundred J, Tan BH. Body composition assessment and sarcopenia in patients with gastric cancer: a systematic review and meta-analysis. Gastric Cancer 2018; 1-13. Kamarajah SK, Bundred J, Tan BH. Body composition assessment and sarcopenia in patients with gastric cancer: a systematic review and meta-analysis. Gastric Cancer 2018; 1-13.
23.
go back to reference Fukushima H, Takemura K, Suzuki H, Koga F. Impact of Sarcopenia as a Prognostic Biomarker of Bladder Cancer. Int J Mol Sci. 2018;19:2999.CrossRef Fukushima H, Takemura K, Suzuki H, Koga F. Impact of Sarcopenia as a Prognostic Biomarker of Bladder Cancer. Int J Mol Sci. 2018;19:2999.CrossRef
24.
go back to reference Chang K-V, Chen J-D, Wu W-T, et al. Association between Loss of Skeletal Muscle Mass and Mortality and Tumor Recurrence in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Liver cancer. 2018;7:90–103.CrossRef Chang K-V, Chen J-D, Wu W-T, et al. Association between Loss of Skeletal Muscle Mass and Mortality and Tumor Recurrence in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Liver cancer. 2018;7:90–103.CrossRef
25.
go back to reference Ozola Zalite I, Zykus R, Francisco Gonzalez M, et al. Influence of cachexia and sarcopenia on survival in pancreatic ductal adenocarcinoma: a systematic review. Pancreatology. 2015;15:19–24.CrossRef Ozola Zalite I, Zykus R, Francisco Gonzalez M, et al. Influence of cachexia and sarcopenia on survival in pancreatic ductal adenocarcinoma: a systematic review. Pancreatology. 2015;15:19–24.CrossRef
26.
go back to reference Deng HY, Hou L, Zha P et al. Sarcopenia is an independent unfavorable prognostic factor of non-small cell lung cancer after surgical resection: A comprehensive systematic review and meta-analysis. Eur J Surg Oncol 2018. Deng HY, Hou L, Zha P et al. Sarcopenia is an independent unfavorable prognostic factor of non-small cell lung cancer after surgical resection: A comprehensive systematic review and meta-analysis. Eur J Surg Oncol 2018.
27.
go back to reference van Vledder MG, Levolger S, Ayez N, et al. Body composition and outcome in patients undergoing resection of colorectal liver metastases. Br J Surg. 2012;99:550–7.CrossRef van Vledder MG, Levolger S, Ayez N, et al. Body composition and outcome in patients undergoing resection of colorectal liver metastases. Br J Surg. 2012;99:550–7.CrossRef
28.
go back to reference Miyamoto Y, Suyama K, Baba H. Recent Advances in Targeting the EGFR Signaling Pathway for the Treatment of Metastatic Colorectal Cancer. Int J Mol Sci 2017; 18. Miyamoto Y, Suyama K, Baba H. Recent Advances in Targeting the EGFR Signaling Pathway for the Treatment of Metastatic Colorectal Cancer. Int J Mol Sci 2017; 18.
29.
go back to reference Hodson N, Philp A. The Importance of mTOR Trafficking for Human Skeletal Muscle Translational Control. Exerc Sport Sci Rev. 2019;47:46–53.CrossRef Hodson N, Philp A. The Importance of mTOR Trafficking for Human Skeletal Muscle Translational Control. Exerc Sport Sci Rev. 2019;47:46–53.CrossRef
30.
go back to reference Zhang Q, Duplany A, Moncollin V et al. Lack of muscle mTOR kinase activity causes early onset myopathy and compromises whole-body homeostasis. 2018. Zhang Q, Duplany A, Moncollin V et al. Lack of muscle mTOR kinase activity causes early onset myopathy and compromises whole-body homeostasis. 2018.
31.
go back to reference Yoon MS. mTOR as a Key Regulator in Maintaining Skeletal Muscle Mass. Front Physiol. 2017;8:788.CrossRef Yoon MS. mTOR as a Key Regulator in Maintaining Skeletal Muscle Mass. Front Physiol. 2017;8:788.CrossRef
32.
go back to reference Gyawali B, Shimokata T, Honda K, et al. Muscle wasting associated with the long-term use of mTOR inhibitors. Mol Clin Oncol. 2016;5:641–6.CrossRef Gyawali B, Shimokata T, Honda K, et al. Muscle wasting associated with the long-term use of mTOR inhibitors. Mol Clin Oncol. 2016;5:641–6.CrossRef
33.
go back to reference Blauwhoff-Buskermolen S, Versteeg KS, de van der Schueren MA et al. Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer. J Clin Oncol 2016; 34: 1339-1344.CrossRef Blauwhoff-Buskermolen S, Versteeg KS, de van der Schueren MA et al. Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer. J Clin Oncol 2016; 34: 1339-1344.CrossRef
Metadata
Title
Skeletal muscle loss during anti-EGFR combined chemotherapy regimens predicts poor prognosis in patients with RAS wild metastatic colorectal cancer
Authors
O. Köstek
N. C. Demircan
A. Gökyer
A. Küçükarda
B. S. Sunal
M. B. Hacıoğlu
H. Eslame
S. Solak
E. Yılmaz
S. Uzunoğlu
N. Tunçbilek
İ. Çiçin
B. Erdoğan
Publication date
01-11-2019
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 11/2019
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-019-02079-x

Other articles of this Issue 11/2019

Clinical and Translational Oncology 11/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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