Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study

Abstract

BackgroundIn the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates.Methodology/Principal FindingsKRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI:1.12–1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23–1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18–2.64).Conclusions/SignificanceThis analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

S3-Leitlinie – Kolorektales Karzinom

“…In der MACRO-sowie auch der CAIRO3-Studie wurden vor Beginn der Erhaltungstherapie 6 Zyklen CAPOX (4,5 Monate) gegeben [1146,1147]. In der AIO KRK-0207-Studie folgte die Erhaltungstherapie einer über 6 Monate durchgeführ-ten Induktionstherapie [1148].…”

The prevalent KRAS exon 2 c.35 G>A mutation in metastatic colorectal cancer patients: A biomarker of worse prognosis and potential benefit of bevacizumab-containing intensive regimens?

“…Recently KRAS exon 2 genotype was reported as significantly affecting PFS and OS in patients treated with XelOx/BEV [55].…”

Relevance of CEA and LDH in relation to KRAS status in patients with unresectable colorectal liver metastases.

“…Studies have found that patients with KRAS mutated tumors have a lower recurrence free survival and lower overall survival (OS) rate compared to patients with wild-type tumors [3,[5][6][7]. LDH is a metabolic enzyme that catalyzes the conversion of pyruvate to lactate under anaerobic conditions and is overproduced in cancer cells [8].…”