Dynamics in treatment response and disease progression of metastatic colorectal cancer (mCRC) patients with focus on BRAF status and primary tumor location: analysis of untreated RAS-wild-type mCRC patients receiving FOLFOXIRI either with or without panitumumab in the VOLFI trial (AIO KRK0109)

  1. Kurreck, A.
  2. Geissler, M.
  3. Martens, U. M.
  4. Riera-Knorrenschild, J.
  5. Greeve, J.
  6. Florschütz, A.
  7. Wessendorf, S.
  8. Ettrich, T.
  9. Kanzler, S.
  10. Nörenberg, D.
  11. Seidensticker, M.
  12. Held, S.
  13. Buechner-Steudel, P.
  14. Atzpodien, J.
  15. Heinemann, V.
  16. Stintzing, S.
  17. Seufferlein, T.
  18. Tannapfel, A.
  19. Reinacher-Schick, A. C.
  20. Modest, Dominik Paul ORCID logo

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1000 Titel
  • Dynamics in treatment response and disease progression of metastatic colorectal cancer (mCRC) patients with focus on BRAF status and primary tumor location: analysis of untreated RAS-wild-type mCRC patients receiving FOLFOXIRI either with or without panitumumab in the VOLFI trial (AIO KRK0109)
1000 Autor/in
  1. Kurreck, A. |
  2. Geissler, M. |
  3. Martens, U. M. |
  4. Riera-Knorrenschild, J. |
  5. Greeve, J. |
  6. Florschütz, A. |
  7. Wessendorf, S. |
  8. Ettrich, T. |
  9. Kanzler, S. |
  10. Nörenberg, D. |
  11. Seidensticker, M. |
  12. Held, S. |
  13. Buechner-Steudel, P. |
  14. Atzpodien, J. |
  15. Heinemann, V. |
  16. Stintzing, S. |
  17. Seufferlein, T. |
  18. Tannapfel, A. |
  19. Reinacher-Schick, A. C. |
  20. Modest, Dominik Paul |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-05-24
1000 Erschienen in
1000 Quellenangabe
  • 146(10):2681-2691
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00432-020-03257-z |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467910/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Purpose!#!In mCRC, disease dynamics may play a critical role in the understanding of long-term outcome. We evaluated depth of response (DpR), time to DpR, and post-DpR survival as relevant endpoints.!##!Methods!#!We analyzed DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), early tumor shrinkage (≥ 20% reduction in tumor diameter at first reassessment), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR-image to tumor progression or death), and post-DpR overall survival (pOS = DpR-image to death) with special focus on BRAF status in 66 patients and primary tumor site in 86 patients treated within the VOLFI-trial, respectively.!##!Results!#!BRAF wild-type (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (- 57.6% vs. - 40.8%, p = 0.013) with a comparable time to DpR [4.0 (95% CI 3.1-4.4) vs. 3.9 (95% CI 2.5-5.5) months; p = 0.8852]. pPFS was 6.5 (95% CI 4.9-8.0) versus 2.6 (95% CI 1.2-4.0) months in favor of BRAF-WT patients (HR 0.24 (95% CI 0.11-0.53); p < 0.001). This transferred into a significant difference in pOS [33.6 (95% CI 26.0-41.3) vs. 5.4 (95% CI 5.0-5.9) months; HR 0.27 (95% CI 0.13-0.55); p < 0.001]. Similar observations were made for patients stratified for primary tumor site.!##!Conclusions!#!BRAF-MT patients derive a less profound treatment response compared to BRAF-WT patients. The difference in outcome according to BRAF status is evident after achievement of DpR with BRAF-MT patients hardly deriving any further disease control beyond DpR. Our observations hint towards an aggressive tumor evolution in BRAF-MT tumors, which may already be molecularly detectable at the time of DpR.
1000 Sacherschließung
lokal Leucovorin/administration
lokal Disease Progression [MeSH]
lokal Aged [MeSH]
lokal Proto-Oncogene Proteins B-raf/genetics [MeSH]
lokal Original Article – Clinical Oncology
lokal ras Proteins/genetics [MeSH]
lokal Combination chemotherapy
lokal Early tumor shrinkage
lokal Camptothecin/analogs
lokal Disease dynamics
lokal Depth of response
lokal Male [MeSH]
lokal Metastatic colorectal cancer
lokal Camptothecin/administration
lokal Fluorouracil/administration
lokal Female [MeSH]
lokal Panitumumab/administration
lokal Mutation [MeSH]
lokal Adult [MeSH]
lokal Humans [MeSH]
lokal Neoplasm Metastasis [MeSH]
lokal Treatment Outcome [MeSH]
lokal Colorectal Neoplasms/drug therapy [MeSH]
lokal BRAF
lokal Middle Aged [MeSH]
lokal Antineoplastic Combined Chemotherapy Protocols/administration
lokal Antineoplastic Combined Chemotherapy Protocols/therapeutic use [MeSH]
lokal Organoplatinum Compounds/administration
lokal Primary tumor site
lokal Colorectal Neoplasms/enzymology [MeSH]
lokal Colorectal Neoplasms/pathology [MeSH]
lokal Colorectal Neoplasms/genetics [MeSH]
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/S3VycmVjaywgQS4=|https://frl.publisso.de/adhoc/uri/R2Vpc3NsZXIsIE0u|https://frl.publisso.de/adhoc/uri/TWFydGVucywgVS4gTS4=|https://frl.publisso.de/adhoc/uri/UmllcmEtS25vcnJlbnNjaGlsZCwgSi4=|https://frl.publisso.de/adhoc/uri/R3JlZXZlLCBKLg==|https://frl.publisso.de/adhoc/uri/RmxvcnNjaMO8dHosIEEu|https://frl.publisso.de/adhoc/uri/V2Vzc2VuZG9yZiwgUy4=|https://frl.publisso.de/adhoc/uri/RXR0cmljaCwgVC4=|https://frl.publisso.de/adhoc/uri/S2FuemxlciwgUy4=|https://frl.publisso.de/adhoc/uri/TsO2cmVuYmVyZywgRC4=|https://frl.publisso.de/adhoc/uri/U2VpZGVuc3RpY2tlciwgTS4=|https://frl.publisso.de/adhoc/uri/SGVsZCwgUy4=|https://frl.publisso.de/adhoc/uri/QnVlY2huZXItU3RldWRlbCwgUC4=|https://frl.publisso.de/adhoc/uri/QXR6cG9kaWVuLCBKLg==|https://frl.publisso.de/adhoc/uri/SGVpbmVtYW5uLCBWLg==|https://frl.publisso.de/adhoc/uri/U3RpbnR6aW5nLCBTLg==|https://frl.publisso.de/adhoc/uri/U2V1ZmZlcmxlaW4sIFQu|https://frl.publisso.de/adhoc/uri/VGFubmFwZmVsLCBBLg==|https://frl.publisso.de/adhoc/uri/UmVpbmFjaGVyLVNjaGljaywgQS4gQy4=|https://orcid.org/0000-0002-6853-0599
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1000 Erstellt am 2023-11-17T11:42:00.664+0100
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