nach oben

Erschienen in:

24.10.2017 | Original Research Article

CEA Response and Depth of Response (DpR) to Predict Clinical Outcomes of First-Line Cetuximab Treatment for Metastatic Colorectal Cancer

verfasst von: Yu Sunakawa, Akihito Tsuji, Tadamichi Denda, Yoshihiko Segawa, Yuji Negoro, Ken Shimada, Mitsugu Kochi, Masato Nakamura, Masahito Kotaka, Hiroaki Tanioka, Akinori Takagane, Satoshi Tani, Tatsuro Yamaguchi, Takanori Watanabe, Masahiro Takeuchi, Masashi Fujii, Wataru Ichikawa

Erschienen in: Targeted Oncology | Ausgabe 6/2017

Einloggen, um Zugang zu erhalten

Abstract

Background

The decrease in carcinoembryonic antigen (CEA) level is faster and greater during cetuximab treatment than bevacizumab treatment and correlates with prolonged survival in patients with metastatic colorectal cancer (mCRC) who receive cetuximab.

Objective

We investigated if the degree of change in the CEA value can serve as a diagnostic tool for predicting survival, as well as tumor regression in mCRC patients treated with cetuximab combined regimen as first-line treatment.

Patients and Methods

Associations among the CEA decrease, depth of response (DpR), and clinical outcomes were evaluated in 113 patients with mCRC from two phase II trials of first-line therapy: the JACCRO CC-05 trial of cetuximab plus FOLFOX and the CC-06 trial of cetuximab plus SOX. Analysis was performed using Spearman’s rank correlation coefficient. A 75% decrease in the CEA was used as the cut-off value to define the CEA response and discriminate CEA responders on the basis of the results of a previous study.

Results

Ninety-two patients were eligible for analyses of both CEA and DpR. The median CEA decrease was 67.4%, and the median time to CEA nadir was 2.8 months, which was similar to the median time to DpR of 3.0 months. The DpR was associated with PFS and OS (r_s = 0.56, P < 0.0001; r_s = 0.39, P = 0.0090, respectively); moreover, the CEA decrease correlated with PFS (r_s = 0.56, P < 0.0001), as well as OS (r_s = 0.35, P = 0.019). CEA responders had significantly longer PFS (11.8 vs. 5.5 months, hazard ratio [HR] 0.46, P = 0.0009) and slightly, but not significantly longer OS (36.2 vs. 23.5 months; HR 0.57; P = 0.072) than CEA non-responders. The CEA decrease was statistically significantly associated with the DpR (r_s = 0.44, P < 0.0001).

Conclusions

Our study demonstrates that both DpR and CEA response correlate with clinical outcomes of first-line treatment with cetuximab. The CEA decrease may serve as a surrogate for DpR in patients who receive first-line cetuximab treatment (UMIN000004197, UMIN000007022).

Nur mit Berechtigung zugänglich

De Roock W, Jonker DJ, Di Nicolantonio F, Sartore-Bianchi A, Tu D, Siena S, et al. Association of KRAS p.G13D Mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA. 2010;304:1812–20.CrossRefPubMed

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;369:1023–34.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;15:1065–75.CrossRefPubMed

Compton CC, Fielding LP, Burgart LJ, Conley B, Cooper HS, Hamilton SR, et al. Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000;124:979–94.PubMed

Carriquiry LA, Pineyro A. Should carcinoembryonic antigen be used in the management of patients with colorectal cancer? Dis Colon Rectum. 1999;42:921–9.CrossRefPubMed

Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. 1965;122:467–81.CrossRefPubMedPubMedCentral

Duffy MJ, van Dalen A, Haglund C, Hansson L, Holinski-Feder E, Klapdor R, et al. Tumour markers in colorectal cancer: European group on tumour markers (EGTM) guidelines for clinical use. Eur J Cancer. 2007;43:1348–60.CrossRefPubMed

Fortner JG, Silva JS, Golbey RB, Cox EB, Maclean BJ. Multivariate analysis of a personal series of 247 consecutive patients with liver metastases from colorectal cancer. I. Treatment by hepatic resection. Ann Surg. 1984;199:306–16.CrossRefPubMedPubMedCentral

Dhar P, Moore T, Zamcheck N, Kupchik HZ. Carcinoembryonic antigen (CEA) in colonic cancer. Use in preoperative and postoperative diagnosis and prognosis. JAMA. 1972;221:31–5.CrossRefPubMed

10.

Duffy MJ, van Dalen A, Haglund C, Hansson L, Klapdor R, Lamerz R, et al. Clinical utility of biochemical markers in colorectal cancer: European group on tumour markers (EGTM) guidelines. Eur J Cancer. 2003;39:718–27.CrossRefPubMed

11.

Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006;24:5313–27.CrossRefPubMed

12.

Sepulveda AR, Hamilton SR, Allegra CJ, Grody W, Cushman-Vokoun AM, Funkhouser WK, et al. Molecular biomarkers for the evaluation of colorectal cancer: guideline from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017;35:1453–86.

13.

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;27:1386–422.CrossRefPubMed

14.

Engstrom PF, Arnoletti JP, Benson AB 3rd, Chen YJ, Choti MA, Cooper HS, et al. NCCN clinical practice guidelines in oncology: colon cancer. J Natl Compr Cancer Netw. 2009;7:778–831.CrossRef

15.

Preketes AP, King J, Caplehorn JR, Clingan PR, Ross WB, Morris DL. CEA reduction after cryotherapy for liver metastases from colon cancer predicts survival. Aust N Z J Surg. 1994;64:612–4.CrossRefPubMed

16.

Ward U, Primrose JN, Finan PJ, Perren TJ, Selby P, Purves DA, et al. The use of tumour markers CEA, CA-195 and CA-242 in evaluating the response to chemotherapy in patients with advanced colorectal cancer. Br J Cancer. 1993;67:1132–5.CrossRefPubMedPubMedCentral

17.

Iwanicki-Caron I, Di Fiore F, Roque I, Astruc E, Stetiu M, Duclos A, et al. Usefulness of the serum carcinoembryonic antigen kinetic for chemotherapy monitoring in patients with unresectable metastasis of colorectal cancer. J Clin Oncol. 2008;26:3681–6.CrossRefPubMed

18.

Michl M, Koch J, Laubender RP, Modest DP, Giessen C, Schulz C, et al. Tumor markers CEA and CA 19-9 correlate with radiological imaging in metastatic colorectal cancer patients receiving first-line chemotherapy. Tumour Biol. 2014;35:10121–7.CrossRefPubMed

19.

Huang SC, Lin JK, Lin TC, Chen WS, Yang SH, Wang HS, et al. Concordance of Carcinoembryonic antigen ratio and response evaluation criteria in solid tumors as prognostic surrogate indicators of metastatic colorectal cancer patients treated with chemotherapy. Ann Surg Oncol. 2015;22:2262–8.CrossRefPubMed

20.

Michl M, Stintzing S, Fischer von Weikersthal L, Decker T, Kiani A, Vehling-Kaiser U, et al. CEA response is associated with tumor response and survival in patients with KRAS exon 2 wild-type and extended RAS wild-type metastatic colorectal cancer receiving first-line FOLFIRI plus cetuximab or bevacizumab (FIRE-3 trial). Ann Oncol. 2016;27:1565–72.CrossRefPubMed

21.

Heinemann V, Stintzing S, Modest DP, Giessen-Jung C, Michl M, Mansmann UR. Early tumour shrinkage (ETS) and depth of response (DpR) in the treatment of patients with metastatic colorectal cancer (mCRC). Eur J Cancer. 2015;51:1927–36.CrossRefPubMed

22.

Cremolini C, Loupakis F, Antoniotti C, Lonardi S, Masi G, Salvatore L, et al. Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest. Ann Oncol. 2015;26:1188–94.CrossRefPubMed

23.

Mansmann UR, Laubender RP. Methodologic diligence is needed to define and validate tumor-size response metrics to predict overall survival in first-line metastatic colorectal cancer. J Clin Oncol. 2013;31:4373–4.CrossRefPubMed

24.

Mayer RJ, Garnick MB, Steele GD Jr, Zamcheck N. Carcinoembryonic antigen (CEA) as a monitor of chemotherapy in disseminated colorectal cancer. Cancer. 1978;42:1428–33.CrossRefPubMed

25.

Fakih MG, Padmanabhan A. CEA monitoring in colorectal cancer. What you should know. Oncology (Williston Park). 2006;20:579–87.

26.

Missiaglia E, Jacobs B, D’Ario G, Di Narzo AF, Soneson C, Budinska E, et al. Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol. 2014;25:1995–2001.CrossRefPubMed

27.

Heinemann V, Modest DP, Fischer von Weikersthal L, Decker T, Kiani A, Vehling-Kaiser U, et al. Gender and tumor location as predictors for efficacy: influence on endpoints in first-line treatment with FOLFIRI in combination with cetuximab or bevacizumab in the AIO KRK 0306 (FIRE3) trial. J Clin Oncol. 2014;32(5 suppl; abstr 3600).

28.

von Einem JC, Heinemann V, von Weikersthal LF, Vehling-Kaiser U, Stauch M, Hass HG, et al. Left-sided primary tumors are associated with favorable prognosis in patients with KRAS codon 12/13 wild-type metastatic colorectal cancer treated with cetuximab plus chemotherapy: an analysis of the AIO KRK-0104 trial. J Cancer Res Clin Oncol. 2014;140:1607–14.CrossRef

29.

Sunakawa Y, Ichikawa W, Tsuji A, Denda T, Segawa Y, Negoro Y, et al. Prognostic impact of primary tumor location on clinical outcomes of metastatic colorectal cancer treated with Cetuximab plus Oxaliplatin-based chemotherapy: a subgroup analysis of the JACCRO CC-05/06 trials. Clin Colorectal Cancer. 2017;16:e171–e180.

Titel: CEA Response and Depth of Response (DpR) to Predict Clinical Outcomes of First-Line Cetuximab Treatment for Metastatic Colorectal Cancer
verfasst von: Yu Sunakawa
Akihito Tsuji
Tadamichi Denda
Yoshihiko Segawa
Yuji Negoro
Ken Shimada
Mitsugu Kochi
Masato Nakamura
Masahito Kotaka
Hiroaki Tanioka
Akinori Takagane
Satoshi Tani
Tatsuro Yamaguchi
Takanori Watanabe
Masahiro Takeuchi
Masashi Fujii
Wataru Ichikawa
Publikationsdatum: 24.10.2017
Verlag: Springer International Publishing
Erschienen in: Targeted Oncology / Ausgabe 6/2017
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-017-0527-0

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

CEA Response and Depth of Response (DpR) to Predict Clinical Outcomes of First-Line Cetuximab Treatment for Metastatic Colorectal Cancer

Abstract

Background

Objective

Patients and Methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Background

Objective

Patients and Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2017

Author’s Reply to Arnaud Uguen: “Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical Characteristics and Management in a Real-Life Setting: a French Retrospective Analysis (GFPC 02–14 Study)”

Validation of a Simple Scoring System to Predict Sorafenib Effectiveness in Patients with Hepatocellular Carcinoma

Targeting Anaplastic Lymphoma Kinase (ALK) in Rhabdomyosarcoma (RMS) with the Second-Generation ALK Inhibitor Ceritinib

Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical Characteristics and Management in a Real-Life Setting: a French Retrospective Analysis (GFPC 02–14 Study)

Comment on: “Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical Characteristics and Management in a Real-Life Setting: a French Retrospective Analysis (GFPC 02–14 Study)”

Antibody–Drug Conjugates for the Treatment of Solid Tumors: Clinical Experience and Latest Developments

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie