Dataset Information

Impact of encorafenib on survival of patients with BRAF^V600E-mutant metastatic colorectal cancer in a real-world setting.

ABSTRACT:

Purpose

Patients with BRAF^V600E-mutant metastatic colorectal cancer (mCRC) have a dismal prognosis. The best strategies in these patients remain elusive. Against this background, we report the clinical course of patients with BRAF^V600E-mutant mCRC to retrieve the best treatment strategy.

Patients and methods

Clinico-pathological data were extracted from the electronic health records. Kaplan-Meier method was used to estimate overall (OS) and progression-free survival (PFS). Objective response rate (ORR) was assessed according to RECIST 1.1.

Results

In total, 51 patients were enrolled. FOLFOXIRI was administered to 12 patients; 29 patients received FOLFOX or FOLFIRI as first-line treatment. Median OS was 17.6 months. Median PFS with FOLFOXIRI (13.0 months) was significantly prolonged (HR 0.325) as compared to FOLFOX/FOLFIRI (4.3 months). However, this failed to translate into an OS benefit (p = 0.433). Interestingly, addition of a monoclonal antibody to chemotherapy associated with superior OS (HR 0.523). A total of 64.7% patients received further-line therapy, which included a BRAF inhibitor in 17 patients. Targeted therapy associated with very favourable OS (25.1 months).

Conclusion

Patients with BRAF^V600E-mutated mCRC benefit from the addition of an antibody to first-line chemotherapy. Further-line treatment including a BRAF inhibitor has a dramatic impact on survival.

SUBMITTER: Zurloh M

PROVIDER: S-EPMC10587317 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Impact of encorafenib on survival of patients with BRAF<sup>V600E</sup>-mutant metastatic colorectal cancer in a real-world setting.

Zurloh M M Goetz M M Herold T T Treckmann J J Markus P P Schumacher B B Albers D D Rink A A Rosery V V Zaun G G Kostbade K K Pogorzelski M M Ting S S Schmidt H H Stiens R R Wiesweg M M Schuler M M Kasper Stefan S Virchow I I

Journal of cancer research and clinical oncology 20230719 14

<h4>Purpose</h4>Patients with BRAF<sup>V600E</sup>-mutant metastatic colorectal cancer (mCRC) have a dismal prognosis. The best strategies in these patients remain elusive. Against this background, we report the clinical course of patients with BRAF<sup>V600E</sup>-mutant mCRC to retrieve the best treatment strategy.<h4>Patients and methods</h4>Clinico-pathological data were extracted from the electronic health records. Kaplan-Meier method was used to estimate overall (OS) and progression-free s ...[more]

PMID: 37466791

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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:BackgroundThe combination of encorafenib with cetuximab has become the standard of care in patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC) after a prior systemic therapy. This study aims to describe the efficacy and safety of encorafenib/cetuximab +/- binimetinib in patients with BRAF V600E-mutated mCRC in a real-world setting.Patients and methodsThis retrospective study included patients with BRAF V600E-mutated mCRC who received this combination from January 2020 to June 2022 in 30 centers.ResultsA total of 201 patients were included, with 55% of women, a median age of 62 years, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) >1 in 20% of cases. The main tumor characteristics were 60% of right-sided primary tumor, 11% of microsatellite instability/mismatch repair deficient phenotype, and liver and peritoneum being the two main metastatic sites (57% and 51%). Encorafenib/cetuximab +/- binimetinib was prescribed in the first, second, third, and beyond third line in 4%, 56%, 29%, and 11%, respectively, of cases, with the encorafenib/cetuximab/binimetinib combination for 21 patients (10%). With encorafenib/cetuximab treatment, 21% of patients experienced grade ≥3 adverse events (AEs), with each type of grade ≥3 AE observed in <5% of patients. The objective response rate was 32.2% and the disease control rate (DCR) was 71.2%. The median progression-free survival (PFS) was 4.5 months [95% confidence interval (CI) 3.9-5.4 months] and the median overall survival (OS) was 9.2 months (95% CI 7.8-10.8 months). In multivariable analysis, factors associated with a shorter PFS were synchronous metastases [hazard ratio (HR) 1.66, P = 0.04] and ECOG-PS >1 (HR 1.88, P = 0.007), and those associated with a shorter OS were the same factors (HR 1.71, P = 0.03 and HR 2.36, P < 0.001, respectively) in addition to treatment beyond the second line (HR 1.74, P = 0.003) and high carcinoembryonic antigen level (HR 1.72, P = 0.003).ConclusionThis real-world study showed that in patients with BRAF V600E-mutated mCRC treated with encorafenib/cetuximab +/- binimetinib, efficacy and safety data confirm those reported in the BEACON registration trial. The main poor prognostic factors for this treatment are synchronous metastases and ECOG-PS >1.

Dataset Information

Impact of encorafenib on survival of patients with BRAF^V600E-mutant metastatic colorectal cancer in a real-world setting.

Purpose

Patients and methods

Results

Conclusion

Publications

Impact of encorafenib on survival of patients with BRAF<sup>V600E</sup>-mutant metastatic colorectal cancer in a real-world setting.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Impact of encorafenib on survival of patients with BRAFV600E-mutant metastatic colorectal cancer in a real-world setting.

Purpose

Patients and methods

Results

Conclusion

Publications

Impact of encorafenib on survival of patients with BRAF<sup>V600E</sup>-mutant metastatic colorectal cancer in a real-world setting.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Impact of encorafenib on survival of patients with BRAF^V600E-mutant metastatic colorectal cancer in a real-world setting.