Survival outcomes in patients with RAS wild type metastatic colorectal cancer classified according to Kohne prognostic category and BRAF mutation status
There is a need to identify patients who may benefit from particular treatments. We investigated prognosis in 915 patients with mCRC from 2 phase III trials of panitumumab plus chemotherapy, based on Kohne category and BRAF status. Both Kohne category and BRAF status predicted outcomes in terms of PFS and OS, and panitumumab provided benefits over chemotherapy alone. Background: Kohne prognostic score is used to classify patients with metastatic colorectal cancer (mCRC) as high, intermediate, or low risk. Using data from 2 phase III trials, we analyzed survival in patients categorized according to Kohne prognostic category and virus-induced rapidly accelerated fibrosarcoma murine sarcoma viral oncogene homolog B (BRAF) mutation. Patients and Methods: PRIME (Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy) (first-line) and 20050181 (second-line) were studies of chemotherapy with or without panitumumab. Progression-free survival (PFS) and overall survival (OS) were analyzed retrospectively in rat sarcoma viral oncogene homolog (RAS) wild type (WT) and RAS WT+BRAF WT mCRC in each Kohne category, and in BRAF mutant (MT) mCRC. Results: In PRIME (n = 495) and 20050181 (n = 420), 53 (11%) and 44 (10%) patients, respectively, had BRAF MT mCRC. Of the RAS WT+BRAF WT/unknown populations, 85/267/90 and 82/211/83 were categorized as high/medium/low risk, respectively. PFS and OS hazard ratios (HRs), adjusted for Kohne group, for patients with RAS WT + BRAF WT/unknown mCRC favored panitumumab with chemotherapy versus chemotherapy alone in both studies. In PRIME, the PFS HR was 0.74 (95% confidence interval [CI], 0.61-0.90) and OS HR was 0.78 (95% CI, 0.64-0.95). In 20050181, PFS and OS HRs were 0.80 (95% CI, 0.65-0.99) and 0.78 (95% CI, 0.62-0.99), respectively. Median PFS and OS were lower in patients with BRAF MT mCRC than in any of the 3 risk categories for patients with RAS WT+BRAF WT/unknown mCRC. Conclusion: During first- and second-line treatment, Kohne prognostic score allows accurate risk classification in RAS WT mCRC. BRAF MT mCRC should be classified as high risk regardless of other parameters. Panitumumab with chemotherapy might provide survival benefits versus chemotherapy alone in RAS WT and RAS WT+BRAF WT/unknown mCRC, overall and across risk categories. (C) 2017 The Authors. Published by Elsevier Inc.
Source (journal)
Clinical colorectal cancer
17:1(2018), p. 50-57
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Full text (open access)
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Publications with a UAntwerp address
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Web of Science
Creation 29.03.2018
Last edited 15.07.2021
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