Universität zu Köln

Modest, Dominik Paul, Heinemann, Volker, Folprecht, Gunnar, Denecke, Timm, Pratschke, Johann, Lang, Hauke, Bemelmans, Marc, Becker, Thomas, Rentsch, Markus, Seehofer, Daniel, Bruns, Christiane J., Gebauer, Bernhard, Held, Swantje, Stahler, Arndt, Heinrich, Kathrin, von Einem, Jobst C., Stintzing, Sebastian, Neumann, Ulf P. and Ricard, Ingrid (2020). Factors That Influence Conversion to Resectability and Survival After Resection of Metastases in RAS WT Metastatic Colorectal Cancer (mCRC): Analysis of FIRE-3-AIOKRK0306. Ann. Surg. Oncol., 27 (7). S. 2389 - 2402. NEW YORK: SPRINGER. ISSN 1534-4681

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Abstract

Background Tumor assessments after first-line therapy ofRASwild-type mCRC with cetuximab (cet) versus bevacizumab (bev) in combination with FOLFIRI were evaluated for factors influencing resectability, conversion to resectability, and survival after best response. Methods Conversion to resectability was defined as conversion of initially unresectable to resectable disease at best response as determined by retrospective assessment. Univariate and multivariate logistic models were fitted with resectability at best response as response variable. A Cox model comparing the survival from best response was used to measure the influence of treatment, resectability at best response, and resection. Interaction of resection and treatment arm on survival was tested by likelihood ratio test. Results Overall, 270 patients were evaluable (127 cet-arm, 143 bev-arm). Lung metastases (odds ratio [OR] 0.35, 95% confidence response [CI] 0.19-0.63),BRAFmutation (OR 0.33, 95% CI 0.12-0.82), and elevated alkaline phosphatase (OR 0.42, 95% CI 0.18-0.9) before randomization were associated with less chance of successful conversion and were integrated into a nomogram. Early tumor shrinkage (OR 1.86, 95% CI 1.06-3.3;p 0.034) and depth of response (OR 1.02, 95% CI 1.01-1.03;p < 0.001) were associated with successful conversion therapy. Resection of metastases improved post-best-response survival (hazard ratio 0.53, 95% CI 0.29-0.97;p = 0.039), predominantely in cet-treated patients (interaction test,p = 0.02). Conclusions Conversion to resectability is significantly associated with baseline characteristics that can be used in a nomogram to predict conversion. Moreover, early efficacy parameters (ETS and DpR) are associated with successful conversion therapy. In FIRE-3, resection of metastases was associated with improved post-best response survival, this effect originated predominantly from the cetuximab-based study arm.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Modest, Dominik Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinemann, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Folprecht, Gunnar UNSPECIFIED UNSPECIFIED UNSPECIFIED Denecke, Timm UNSPECIFIED UNSPECIFIED UNSPECIFIED Pratschke, Johann UNSPECIFIED UNSPECIFIED UNSPECIFIED Lang, Hauke UNSPECIFIED UNSPECIFIED UNSPECIFIED Bemelmans, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Rentsch, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Seehofer, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gebauer, Bernhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Held, Swantje UNSPECIFIED UNSPECIFIED UNSPECIFIED Stahler, Arndt UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinrich, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED von Einem, Jobst C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stintzing, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumann, Ulf P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ricard, Ingrid UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-328310
DOI:	10.1245/s10434-020-08219-w
Journal or Publication Title:	Ann. Surg. Oncol.
Volume:	27
Number:	7
Page Range:	S. 2389 - 2402
Date:	2020
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1534-4681
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FOLFIRI PLUS CETUXIMAB; LIVER METASTASES; OPEN-LABEL; 1ST-LINE TREATMENT; RANDOMIZED-TRIALS; BEVACIZUMAB; CHEMOTHERAPY; KRAS; SUBGROUP; THERAPY Multiple languages Oncology; Surgery Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32831