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BRAF^V600E Metastatic Colorectal Cancer: Perspective from a Patient, a Caregiver, and an Oncologist.

ABSTRACT: This article has been co-authored by a patient with right-sided BRAF^V600E metastatic colorectal cancer (mCRC), his caregiver, and an oncologist. Here the patient and caregiver discuss their personal experiences struggling with cancer, including their fears, expectations, and attitudes as the disease progresses. The oncologist describes how patients with BRAF^V600E mCRC are treated and how the management strategy can be balanced to mitigate any side effects. Improved diagnostic techniques and the availability of numerous treatment options, including various chemotherapy schemes and molecular-targeted drugs, can aid rapid implementation of treatment algorithms. The pivotal roles of patients' associations in the general support of patients and those close to them, and in facilitating the link with healthcare professionals, are highlighted in this perspective piece.

SUBMITTER: Gourdin G

PROVIDER: S-EPMC10329954 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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BRAFV600E Metastatic Colorectal Cancer: Perspective from a Patient, a Caregiver, and an Oncologist.

Gourdin Guillaume G Chotel Laure L de la Fouchardière Christelle C

Advances in therapy 20230614 8

This article has been co-authored by a patient with right-sided BRAFV600E metastatic colorectal cancer (mCRC), his caregiver, and an oncologist. Here the patient and caregiver discuss their personal experiences struggling with cancer, including their fears, expectations, and attitudes as the disease progresses. The oncologist describes how patients with BRAFV600E mCRC are treated and how the management strategy can be balanced to mitigate any side effects. Improved diagnost ...[more]

PMID: 37316651

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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:BackgroundCombinatorial inhibition of epidermal growth factor receptor (EGFR) and BRAF shows remarkable clinical benefits in patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC). However, the tumor may inevitably develop resistance to the targeted therapy, thereby limiting the response rate and durability. This study aimed to determine the genetic alterations associated with intrinsic and acquired resistance to EGFR/BRAF inhibitors in BRAF V600E-mutant mCRC.MethodsTargeted sequencing of 520 cancer-related genes was performed in tumor tissues and in plasma samples collected from patients with BRAF V600E-mutant mCRC, who were treated with EGFR/BRAF ± MEK inhibitors, before and after the targeted treatment. Clinical benefit was defined as an objective response or a stable disease lasting longer than the median progression-free survival (PFS).ResultsIn all, 25 patients with BRAF V600E-mutant mCRC were included in this study. Those with RNF43 mutations (n = 8) were more likely to achieve clinical benefit from EGFR/BRAF inhibitors than those with wild-type RNF43 (87.5% versus 37.5%, p = 0.034). Genetic alterations in receptor tyrosine kinase genes (n = 6) were associated with worse PFS (p = 0.005). Among the 23 patients whose disease progressed after the EGFR/BRAF-targeted therapy, at least one acquired resistance-related mutation was detected in 12 patients. Acquired mutations were most frequently observed in the mitogen-activated protein kinase pathway-related genes (n = 9), including KRAS (G12D and Q61H/R), NRAS (Q61L/R/K and amplification), BRAF (amplification), and MEK1 (K57T). MET amplification and PIK3R1 Q579fs mutation emerged in three patients and one patient, respectively, after disease progression.ConclusionMultiple genetic alterations are associated with clinical benefits and resistance to EGFR/BRAF inhibitors in BRAF V600E-mutant mCRC. Our findings provide novel insights into strategies for overcoming resistance to EGFR/BRAF inhibitors in patients with BRAF V600E-mutant mCRC.

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BRAF^V600E Metastatic Colorectal Cancer: Perspective from a Patient, a Caregiver, and an Oncologist.

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BRAF<sup>V600E</sup> Metastatic Colorectal Cancer: Perspective from a Patient, a Caregiver, and an Oncologist.

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