title: Relation of early tumor shrinkage (ETS) observed in first-line treatment to efficacy parameters of subsequent treatment in FIRE-3 (AIOKRK0306).
abstract: We explored the association of early tumor shrinkage (ETS) and non-ETS with efficacy of first-line and consecutive second-line treatment in patients with KRAS wild-type metastatic colorectal cancer treated in FIRE-3. Assessment of tumor shrinkage was based on the sum of longest diameters of target lesions, evaluated after 6 weeks of treatment. Shrinkage was classified as ETS (shrinkage by ≥ 20%), mETS (shrinkage by 0 to <20%), mPD (minor progression >0 to <20%) and PD (progression ≥20%). Overall survival (OS) was 33.2 (95% CI 28.0-38.4) months in ETS patients, while non-ETS was associated with less favorable outcome (mETS 24.0 (95% CI 21.2-26.9) months, mPD 19.0 (95% CI 13.0-25.0) months, PD 12.8 (95% CI 11.1-14.5) months). Differences in PFS of first-line therapy were less pronounced. ETS subgroups defined in first-line therapy also correlated with efficacy of second-line therapy. Progression-free survival in second-line (PFS2nd) was 6.5 months (5.8-7.2) for ETS, and was 5.6 (95% CI 4.7-6.5) months for mETS, 4.9 (95% CI 3.7-6.1) months for mPD and 3.3 (95% CI 2.3-4.3) months for PD. PFS of first-line and PFS2nd showed a linear correlation (Bravais-Pearson coefficient: 0.16, p = 0.006). While ETS is associated with the most favorable outcome, non-ETS represents a heterogeneous subgroup with distinct characteristics of less favorable initial tumor response to treatment. This is the first analysis to demonstrate that early tumor response observed during first-line FOLFIRI-based therapy may also relate to efficacy of second-line treatment. Early response parameters may serve as stratification factors in trials recruiting pretreated patients.
authors.affiliation: Department of Medical Oncology and Comprehensive Cancer Center, University Hospital Grosshadern, Munich, Germany.|German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Dominik P
authors.initials: DP
authors.lastname: Modest
authors.affiliation: Department of Medical Oncology and Comprehensive Cancer Center, University Hospital Grosshadern, Munich, Germany.|German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stintzing
authors.affiliation: Gesundheitszentrum St. Marien, Amberg, Germany.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Fischer von Weikersthal
authors.affiliation: Oncological Practice, Ravensburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
authors.affiliation: Klinikum Bayreuth, Medizinische Klinik IV, Bayreuth, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kiani
authors.affiliation: Oncological Practice, Landshut, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Vehling-Kaiser
authors.affiliation: Department of Hematology and Oncology, Krankenhaus Nordwest, Frankfurt/Main, Germany.
authors.forename: Salah-Eddin
authors.initials: SE
authors.lastname: Al-Batran
authors.affiliation: Department of Medicine II, Städtisches Klinikum Neuss, Neuss, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Heintges
authors.affiliation: Oncological Practice, Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Lerchenmüller
authors.affiliation: Haematology and Oncology, Staedtisches Klinikum Magdeburg, Magdeburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kahl
authors.affiliation: Oncological Practice, Bad Soden, Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Seipelt
authors.affiliation: Department of Medicine I, Klinikum Weiden, Weiden in der Oberpfalz, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Kullmann
authors.affiliation: Department of Internal Medicine I & Comprehensive Cancer Center, Medical University Vienna, Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Scheithauer
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany.|Institute of Pathology University of Munich, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.affiliation: German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany.|Institute of Pathology University of Munich, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.affiliation: Oncological Practice, Kronach, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Stauch
authors.affiliation: Department of Medical Oncology and Comprehensive Cancer Center, University Hospital Grosshadern, Munich, Germany.
authors.forename: Jobst Christian
authors.initials: JC
authors.lastname: von Einem
authors.affiliation: Medical Department 1, Johannes-Gutenberg Universität Mainz, Mainz; University Cancer Center Frankfurt/Mainz, Frankfurt/Mainz, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Moehler
authors.affiliation: ClinAssess GmbH, Leverkusen, Germany.
authors.forename: Swantje
authors.initials: S
authors.lastname: Held
authors.affiliation: Department of Medical Oncology and Comprehensive Cancer Center, University Hospital Grosshadern, Munich, Germany.|German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068818:Cetuximab / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: C117307:KRAS protein, human; D000068258:Bevacizumab; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: KRAS; RAS; bevacizumab; cetuximab; colorectal cancer; early tumor shrinkage; sequence