Progression-Free Survival Remains Poor Over Sequential Lines of Systemic Therapy in Patients With BRAF-Mutated Colorectal Cancer

Abstract

Background BRAF mutations occur in 5–10% of metastatic colorectal cancers and are biomarkers associated with a poor prognosis. However, the outcomes with standard chemotherapy over sequential lines of therapy in a large cohort of patients with BRAF-mutant tumors have not been described. Methods We searched the MD Anderson Cancer Center databases for patients with colorectal cancer patients and identified BRAF mutations between December 2003 and May 2012. Patients were analyzed for clinical characteristics, progression-free survival (PFS), overall survival (OS), and chemotherapeutic agents used. Survival was estimated according to the Kaplan-Meier method. Results Among the 1567 patients tested for BRAF mutations at our institution, 127 (8.1%) had tumors with BRAF mutations. The 71 patients who presented with metastatic disease received a median of 2 lines of chemotherapy. For the first three lines of chemotherapy, median progression-free survivals were 6.3 months (n=69 patients, 95% confidence interval (CI) of 4.9–7.7 months), 2.5 months (n=58, 95% CI of 1.8–3.0 months), and 2.6 months (n=31, 95% CI of 1.0–4.2 months), respectively. Median PFS was not affected by the backbone chemotherapeutic agent in the first-line setting, whether oxaliplatin-based or irinotecan-based (6.4 months vs. 5.4 months, respectively, p-value = 0.99). Conclusions Progression-free survival is expectedly poor for patients with BRAF-mutated metastatic colorectal cancer. Despite the ascertainment bias present (with testing preferentially performed in patients suitable for clinical trials in refractory disease), these data provide historic controls suitable for future study design and support the idea that novel therapeutic options are essential in this population.

Prevalence of RAS mutations and individual variation patterns among patients with metastatic colorectal cancer: A pooled analysis of randomised controlled trials

“…Other studies have reported similar BRAF mutation prevalence in mCRC patients to those we report [10,12,[21][22][23][24][25][26][27]. Our exploratory analysis of BRAF mutation prevalence by demographic and clinical factors found increased prevalence in females versus males, colon versus rectal cancer and in ECOG PS 0 versus 1/2.…”

“…Our exploratory analysis of BRAF mutation prevalence by demographic and clinical factors found increased prevalence in females versus males, colon versus rectal cancer and in ECOG PS 0 versus 1/2. Other studies have reported increased BRAF mutation prevalence in older versus younger patients, females versus males, right-sided versus left-sided and mucinous versus tumours [25,26].…”

“…There are limited data evaluating RAS mutation prevalence by demographic and clinical factors. A single centre longitudinal analysis (484 patients) found no difference in RAS mutation prevalence between genders [25]. Another single centre analysis (1691 tumour samples) did not find a significant association between KRAS mutation rate and gender, although significant differences were observed for tumour sample site, neoplastic cell percentage and tumour stage [29].…”

“…The prevalence of BRAF ranges between 5% and 15% in larger analyses (more than 450 patients) [10,12,16,[21][22][23][24][25][26][27].…”

Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials

“…B mutant aCRC is consistently associated with poor overall survival (OS) and progression free survival (PFS) in case series [1] and randomised controlled trials (RCTs). [2] In a recent RCT of previously untreated aCRC, median OS was 13.4 months in Bmutant patients compared with 37.1 months in and wildBtypes.…”