Dataset Information

Population-based Screening for BRAF ^V600E in Metastatic Colorectal Cancer Reveals Increased Prevalence and Poor Prognosis.

ABSTRACT:

Purpose

BRAF ^V600E mutations portend poor prognosis in metastatic colorectal cancer (mCRC); however, the true prevalence and prognosis are unknown, as unwell patients may not undergo BRAF sequencing.

Experimental design

We reviewed a population-based cohort of 1,898 patients with colorectal cancer that underwent reflexive IHC mismatch repair (MMR) and BRAF ^V600E testing. Outcomes among IHC-detected BRAF ^V600E mCRC (BRAF _IHC) were compared with patients with next-generation sequencing (NGS)-identified BRAF ^V600E-mutated mCRC from two institutions (BRAF _NGS) with patients spanning from 2004 to 2018.

Results

All-stage population prevalence of BRAF ^V600E was 12.5% (238/1,898) and did not differ between early and metastatic stages (P = 0.094). Prevalence among mCRC was 10.6% (61/575), of whom 51 (83.6%) were referred to oncology and 26 (42.6%) had NGS testing. BRAF _IHC had worse median overall survival (mOS) than BRAF _NGS [5.5 vs. 20.4 months; HR, 2.90; 95% confidence interval (CI), 1.89-4.45; P < 0.0001], which persisted in multivariate analysis (P < 0.0001). Across a combined NGS and IHC cohort, BRAF ^V600E tumors with deficient MMR showed worse mOS compared with MMR proficient tumors (8.9 vs. 17.2 months; HR, 1.46; 95% CI, 0.96-2.27; P = 0.043). In this combined cohort, first-line progression-free survival was 5.9 months, with minimal differences between regimens. Within the population-based cohort, attrition between treatment lines was high with only 60.7% receiving first-line chemotherapy and 26.2% receiving second line.

Conclusions

Patients with BRAF ^V600E-mutated mCRC have a worse prognosis than previously suggested, potentially arising from referral bias for testing. High attrition between lines of therapy suggests efficacious therapies need to be prioritized early for patients to benefit.

SUBMITTER: Chu JE

PROVIDER: S-EPMC7484131 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Population-based Screening for <i>BRAF</i> <sup>V600E</sup> in Metastatic Colorectal Cancer Reveals Increased Prevalence and Poor Prognosis.

Chu Jenny E JE Johnson Benny B Kugathasan Laveniya L Morris Van K VK Raghav Kanwal K Swanson Lucas L Lim Howard J HJ Renouf Daniel J DJ Gill Sharlene S Wolber Robert R Karsan Aly A Kopetz Scott S Schaeffer David F DF Loree Jonathan M JM

Clinical cancer research : an official journal of the American Association for Cancer Research 20200622 17

<h4>Purpose</h4><i>BRAF</i> <sup>V600E</sup> mutations portend poor prognosis in metastatic colorectal cancer (mCRC); however, the true prevalence and prognosis are unknown, as unwell patients may not undergo <i>BRAF</i> sequencing.<h4>Experimental design</h4>We reviewed a population-based cohort of 1,898 patients with colorectal cancer that underwent reflexive IHC mismatch repair (MMR) and <i>BRAF</i> <sup>V600E</sup> testing. Outcomes among IHC-detected <i>BRAF</i> <sup>V600E</sup> mCRC (<i>BR ...[more]

PMID: 32571791

Similar Datasets

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.

Dataset Information

Population-based Screening for BRAF ^V600E in Metastatic Colorectal Cancer Reveals Increased Prevalence and Poor Prognosis.

Purpose

Experimental design

Results

Conclusions

Publications

Population-based Screening for <i>BRAF</i> <sup>V600E</sup> in Metastatic Colorectal Cancer Reveals Increased Prevalence and Poor Prognosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Population-based Screening for BRAF V600E in Metastatic Colorectal Cancer Reveals Increased Prevalence and Poor Prognosis.

Purpose

Experimental design

Results

Conclusions

Publications

Population-based Screening for <i>BRAF</i> <sup>V600E</sup> in Metastatic Colorectal Cancer Reveals Increased Prevalence and Poor Prognosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Population-based Screening for BRAF ^V600E in Metastatic Colorectal Cancer Reveals Increased Prevalence and Poor Prognosis.