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BRAF-mutated colorectal cancer confers poor prognosis regardless of other features
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BRAF-mutated advanced colorectal cancer confers a worse prognosis than BRAF wild-type disease, independent of other clinicopathological features known to be prognostic, according to an analysis of clinical trial data in the United Kingdom.
“The mechanism for the poor prognosis is poorly understood, and it is unclear at what point in the advanced colorectal cancer treatment pathway that BRAF-mutant outcomes diverge from wild-types; whilst OS is uniformly poor, less impact is seen with PFS compared with wild-types,” Jenny F. Seligmann, PhD, of the Leeds Institute of Cancer and Pathology, and colleagues wrote. “It has been hypothesized that poor outcomes are secondary to intrinsic chemoresistance but there is a paucity of data describing the outcomes of BRAF-mutant advanced colorectal cancer with chemotherapy alone, particularly beyond the first line.”
Seligmann and colleagues assessed patient data from three randomized trials (n = 2,530). Of these patients, 231 (9.1%) had BRAF-mutated cancer.
Patients with BRAF mutations who received first-line oxaliplatin/fluorouracil therapy had a similar disease control rate as those with wild-type tumors (59.2% vs. 72%; adjusted OR = 0.75; P = .24).
The two groups also had similar PFS (BRAF-mutated, 5.7 months vs. wild-type, 6.3 months; adjusted HR = 1.14; P = .26). However, patients with BRAF mutations had a significantly shorter postprogression survival (4.2 months vs. 9.2 months; adjusted HR = 1.69; P < .001).
Fewer patients with BRAF mutations than wild-type had second-line treatment (33% vs. 51%; P < .001). BRAF mutation was not associated with worse second-line outcomes.
Researchers noted “significant clinical heterogeneity” among patients with BRAF-mutated disease. Nearly a quarter (24.3%) had good PFS from first-line treatment and good postprogression survival (> 6 months for both; OS = 24 months). More than one-third (36.5%) progressed rapidly from first-line treatment and onward (OS = 4.7 months).
“This, the largest and most comprehensive analysis of chemotherapy outcomes in BRAF-mutant colorectal cancer patients, provides new and important information with clinical relevance,” the researchers wrote. “In summary, BRAF mutation confers a markedly worse prognosis independent of associated clinicopathological features. However, in some patients chemotherapy does provide meaningful improvements in outcome throughout treatment lines and translational efforts need to be made to identify them and those who appear to derive no benefit from chemotherapy. Postprogression survival is worse in BRAF-mutant patients and vigilance is required to ensure the appropriate delivery of treatment after first-line progression.” – by Andy Polhamus
Disclosure: The researchers report no relevant financial disclosures.
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