Dataset Information

Real-world treatment and outcomes of patients with metastatic BRAF mutant colorectal cancer.

ABSTRACT:

Background

BRAF mutation occurs in 5%-10% of metastatic colorectal cancers (mCRCs). Patients with BRAF mutant mCRC exhibit a specific metastatic pattern and poor prognosis. Survival outcomes are heterogeneous in cases of mCRC with a BRAF mutation. The optimal first-line therapy is still controversial.

Methods

We retrospectively reviewed the medical records of patients with mCRC between June 2010 and December 2021. Clinicopathologic characteristics, treatment and BRAF mutation testing results were collected. Patients with a BRAF mutation were included. Kaplan-Meier methods and log-rank tests were used to analyze and compare survival. Cox proportional hazards regression was used to establish the predictive nomogram model.

Results

Of the 4475 mCRC, 261 have a BRAF mutation, including 240 V600E and 21 non-V600E mutants. The median overall survival (OS) was 18.2 months in the BRAF V600E mutant group versus 38.0 months in the non-V600E mutant group (p = 0.022). ECOG score, tumor differentiation, liver metastasis, bone metastasis and primary tumor resection were independent prognostic factors for the OS of BRAF V600E mutant mCRC. A nomogram model was established using these factors. The median OS was 39.3 m, 18.2 m and 10.7 m for the low-risk, intermediate-risk and high-risk groups defined by this model, respectively (p < 0.0001). Patients who received first-line triplet chemotherapy ± bevacizumab had comparable progression free survival (PFS) and OS compared with those treated with doublets ± bevacizumab.

Conclusion

BRAF V600E mutant mCRCs exhibit unfavorable and heterogeneous prognosis. The first-line intensive chemotherapy did not confer a marked impact on the PFS and OS.

SUBMITTER: Xu T

PROVIDER: S-EPMC10225206 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

Real-world treatment and outcomes of patients with metastatic BRAF mutant colorectal cancer.

Xu Ting T Li Jian J Wang Zhenghang Z Zhang Xiaotian X Zhou Jun J Lu Zhihao Z Shen Lin L Wang Xicheng X

Cancer medicine 20230313 9

<h4>Background</h4>BRAF mutation occurs in 5%-10% of metastatic colorectal cancers (mCRCs). Patients with BRAF mutant mCRC exhibit a specific metastatic pattern and poor prognosis. Survival outcomes are heterogeneous in cases of mCRC with a BRAF mutation. The optimal first-line therapy is still controversial.<h4>Methods</h4>We retrospectively reviewed the medical records of patients with mCRC between June 2010 and December 2021. Clinicopathologic characteristics, treatment and BRAF mutation test ...[more]

PMID: 36912150

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Project description:BackgroundBRAFV600E mutations occur in 8%-12% of metastatic colorectal cancer (mCRC) cases and are associated with poor survival. European guidelines recommend combination (doublet or triplet) chemotherapy plus bevacizumab in first line. However, an unmet need remains for more effective treatments for these patients.Patients and methodsCAPSTAN CRC is a European, retrospective, multicenter, observational study evaluating real-world treatment practices for patients with BRAFV600E-mutant mCRC treated between 1 January 2016 and 31 January 2020. The primary objective was to describe first-line treatment patterns. Secondary objectives included describing baseline demographics, mutational testing procedures, treatment effectiveness, and safety.ResultsIn total, 255 patients (median age 66.0 years; 58.4% female) with BRAFV600E-mutant unresectable mCRC from seven countries were included. Most had right-sided tumors (52.5%) and presented with synchronous disease at diagnosis (66.4%). Chemotherapy plus targeted therapy (68.7%) was preferred at first line over chemotherapy alone (31.3%). The main first-line treatments were FOLFOX plus bevacizumab (27.1%) and FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan) with/without bevacizumab (27.1%/19.2%). Median duration of first-line treatment was 4.9 months. Overall, 52.5% received second-line treatment. Across all first-line regimens, progression-free survival (PFS) and overall survival were 6.0 [95% confidence interval (CI) 5.3-6.7] months and 12.9 (95% CI 11.6-14.1) months, respectively. Triplet plus targeted therapy was associated with more adverse events (75.0%) compared with triplet chemotherapy alone (50.0%) and doublet chemotherapy alone (36.1%). Multivariate analysis identified low body mass index and presence of three or more metastatic sites as significant prognostic factors for PFS.ConclusionsThis study is, to date, the largest real-world analysis of patients with BRAFV600E-mutant mCRC, providing valuable insights into routine first-line treatment practices for these patients. The data highlight the intrinsic aggressiveness of this disease subgroup, confirming results from previous real-world studies and clinical trials, and stressing the urgent need for more effective treatment options in this setting.

Project description:BackgroundPatients with BRAF 600E mutated mCRC are associated with specific clinicopathological features and poor prognosis. The relative efficacy of first-line FOLFOXIRI triplet chemotherapy or doublet chemotherapy combined with bevacizumab in patients with BRAF 600E mutated mCRC remains controversial.MethodsBRAF V600E-mutated mCRC patients from 3 institutions were included. The clinicopathological characteristics of the enrolled patients were analyzed. Overall survival (OS) of patients was divided into 4 fractions, including 0-25%, 25-50%, 50-75%,75-100% by quartile method. Patients with OS ranging from 0 to 25% were defined as the poor prognosis group, and patients with OS ranging from 75 to 100% were defined as the good prognosis group. A propensity score matching (PSM) analysis was performed to balance the baseline characteristics of patients treated with doublet chemotherapy and triplet chemotherapy combined with bevacizumab. Survival and tumor response of the two regimens were evaluated.ResultsA total of 125 patients with BRAF V600E-mutated mCRC were enrolled. The median OS of BRAF V600E-mutated mCRC was 14.9 months and the median PFS of first-line therapy was 6.1 months. According to the multivariate analysis and the difference in baseline characteristics between the poor prognosis group and the good prognosis group, poor differentiation and liver metastasis were negative independent prognostic factors for OS in patientsx with BRAF V600E-mutated mCRC. Patients treated with first-line triplets had a longer OS than those treated with doublets both before PSM (17.4 months vs. 13.4 months, p = 0.022) and after PSM (17.4 months vs. 10.4 months, p = 0.004). There was no significant benefit between triplet-drug group and doublet-drug group for PFS, ORR and DCR. Subgroup analysis showed that patients in the triplet-drug group had a better prognosis with the following favorable factors: age ≤ 60 years old, PS score of 0-1, liver metastases and multiple organ metastases.ConclusionThe overall prognosis of BRAF V600E mutant mCRC patients is poor. Poor differentiation and liver metastases were negative independent prognostic factors for OS. First-line triplet-drug therapy was associated with better OS, especially in patients with good physical condition and high tumor burden.

Project description:Background and Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality and morbidity worldwide. Bevacizumab was approved for the treatment of metastatic colorectal cancer (mCRC) based on favorable benefit-risk assessments from randomized controlled trials, but evidence on its use in the real-world setting is limited. The aim of the current study is to evaluate the outcomes and safety profile of bevacizumab in mCRC in a real-world setting in Romania. Patients and Methods: This was an observational, retrospective, multicentric, cohort study conducted in Romania that included patients with mCRC treated with bevacizumab as part of routine clinical practice. Study endpoints were progression-free survival, overall survival, adverse events, and patterns of bevacizumab use. Results: A total of 554 patients were included in the study between January 2008 and December 2018. A total of 392 patients (71%) received bevacizumab in the first line and 162 patients (29%) in the second line. Bevacizumab was mostly combined with a capecitabine/oxaliplatin chemotherapy regimen (31.6%). The median PFS for patients treated with bevacizumab was 8.4 months (interquartile range [IQR], 4.7-15.1 months) in the first line and 6.6 months (IQR, 3.8-12.3 months) in the second line. The median OS was 17.7 months (IQR, 9.3-30.6 months) in the first line and 13.5 months (IQR, 6.7-25.2 months) in the second line. Primary tumor resection was associated with a longer PFS and OS. The safety profile of bevacizumab combined with chemotherapy was similar to other observational studies in mCRC. Conclusions: The safety profile of bevacizumab was generally as expected. Although the PFS was generally similar to that reported in other studies, the OS was shorter, probably due to the less frequent use of bevacizumab after disease progression and the baseline patient characteristics. Patients with mCRC treated with bevacizumab who underwent resection of the primary tumor had a higher OS compared to patients with an unresected primary tumor.

Dataset Information

Real-world treatment and outcomes of patients with metastatic BRAF mutant colorectal cancer.

Background

Methods

Results

Conclusion

Publications

Real-world treatment and outcomes of patients with metastatic BRAF mutant colorectal cancer.

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