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

Autor: Sebastian Stintzing, Michael Geissler, J. Greeve, Volker Heinemann, Petra Buechner-Steudel, Annika Kurreck, Jens Atzpodien, Nörenberg Dominik, Swen Wessendorf, Anke Reinacher, Swantje Held, Axel Florschütz, Thomas J. Ettrich, Dominik Paul Modest, Thomas Seufferlein, Stephan Kanzler, Uwe M. Martens, Andrea Tannapfel, Max Seidensticker, Jorge Riera-Knorrenschild
Rok vydání: 2020
Předmět:
Zdroj: Journal of Clinical Oncology. 38:e16055-e16055
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2020.38.15_suppl.e16055
Popis: e16055 Background: In patients with mCRC, dynamics of response and disease progression may play a critical role in the understanding of long-term outcome. Depth of response (DpR), time to DpR and post-DpR survival represent innovative endpoints to evaluate response and disease dynamics. Methods: We evaluated DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), 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 mutational status in 66 patients. Results: BRAF wildtype (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 (BRAF-WT 4.0 (95% CI 3.1-4.4) months vs. BRAF-MT 3.9 months (95% CI 2.5-5.5), p = 0.8852). pPFS was 6.5 (95% CI 4.7-8.4) versus 2.6 (95% CI 1.0-3.9) months in favor of BRAF-WT patients (HR: 0.24 (95% CI 0.11-0.53; p < 0.001). This also transferred into a significant difference in pOS (33.6 (95% CI 30.0-42.1) versus 5.4 (95% CI 4.7-16.1) months, HR: 0.27 (95% CI 0.13- 0.55); p < 0.001). Further data including primary tumor site will be presented at the meeting. Conclusions: BRAF-MT patients treated within the VOLFI-trial derive a less profound response to treatment as compared to BRAF-WT patients. The substantial difference in outcome according to BRAF status is evident after achievement of deepest response with BRAF-MT patients hardly deriving any further disease control beyond DpR. This is reflected by pPFS and pOS. Our observations hint towards aggressive tumor evolution in patients with BRAF-MT-tumors which may already be molecularly detectable at time of DpR. These findings somehow challenge the currently practiced aggressive treatment strategy of FOLFOXIRI-based 1st-line regimens as they may stimulate treatment resistance and suggest that close monitoring of BRAF-MT patients may include the continuous monitoring of clonal evolution.
Databáze: OpenAIRE
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