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)

• Published in: Journal of cancer research and clinical oncology Vol. 146; no. 10; pp. 2681 - 2691
• Main Authors: Kurreck, A., Geissler, M., Martens, U. M., Riera-Knorrenschild, J., Greeve, J., Florschütz, A., Wessendorf, S., Ettrich, T., Kanzler, S., Nörenberg, D., Seidensticker, M., Held, S., Buechner-Steudel, P., Atzpodien, J., Heinemann, V., Stintzing, S., Seufferlein, T., Tannapfel, A., Reinacher-Schick, A. C., Modest, D. P.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2020; Springer Nature B.V
• Subjects: Cancer Research; Colorectal cancer; Colorectal carcinoma; Disease control; Hematology; Immunotherapy; Internal Medicine; Medicine; Medicine & Public Health; Metastases; Monoclonal antibodies; Oncology; Original Article – Clinical Oncology; Original – Clinical Oncology; Survival; Targeted cancer therapy; Tumors; Early tumor shrinkage; Disease dynamics; Combination chemotherapy; Depth of response; Primary tumor site; BRAF; Metastatic colorectal cancer
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-020-03257-z

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.