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Association details:
| Biomarker: | KRAS mutation |
|---|---|
| Cancer: | Colorectal Cancer |
| Drug: | Avastin (bevacizumab) (VEGF-A inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
The Oncology Biomarker Discovery framework reveals cetuximab and bevacizumab response patterns in metastatic colorectal cancer
Published date:
09/04/2023
Excerpt:
Here, we utilise the open-label, randomised phase III trial (FIRE-3, AIO KRK-0306) in metastatic colorectal carcinoma patients, who received either cetuximab or bevacizumab in combination with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI)....KRAS mutated tumours classified as CMS1 tended to show a longer OS compared to wild-type tumours when treated with bevacizumab...In particular, treatment response differed for tumours classified as CMS4 by KRAS status, showing better response for cetuximab in KRAS wild-type and for bevacizumab in KRAS mutated tumours, respectively.
Secondary therapy:
FOLFIRI
DOI:
https://doi.org/10.1038/s41467-023-41011-4
Trial ID:
Source:
Title:
Avastin and chemotherapy followed by a KRAS stratified randomization to maintenance treatment for first line treatment of metastatic colorectal cancer Avastin (en antikropp) och kemoterapi följt av KRAS stratifierad randomisering till underhållsbehandling för behandling av metastatisk kolorektalcancer.
Excerpt:
...Tumor tissue available for determination of KRAS mutational status. ...
Trial ID:
Source:
Title:
Avastin and Chemotherapy Followed by a KRAS Stratified Randomization to Maintenance Treatment for First Line Treatment of Metastatic Colorectal Cancer.
Excerpt:
...- Tumor tissue available for determination of KRAS mutational status...
Trial ID:
More C2 evidence
Source:
Title:
Bevacizumab + Folfox4 or Xelox2 as first- line treatment in colorectal cancer. Randomized phase II study.
Excerpt:
...-Histologically proven diagnosis of colorectal cancer -Mutation Status KRAS -No previous first line chemoterapy treatment - Written informed consent....
Trial ID:
Source:
Title:
Refractory advanced colorectal cancer in the treatment with integrated traditional Chinese and western medicine: a multi-center clinical study
Excerpt:
...RAS mutation (including KRAS, NRAS and HRAS); 5. ...
Trial ID:
Source:
Title:
Neoadjuvant Bevacizumab + Chemotherapy Combined With Short-course Radiotherapy
Excerpt:
...An ARMS-PCR proven KRAS, NRAS mutation, excluding BRAF mutation or microsatellite instablility-High; 3....
Trial ID:
Source:
Title:
A Real World Study to Evaluate Effectiveness of Avastin (Bevacizumab) for First Line Treatment of Patients With Metastatic Colorectal Cancer and Known KRAS Status
Excerpt:
...Overall Survival (OS) in Participants With mCRC and a Documented KRAS Mutation who Received Bevacizumab-Containing Treatment or Chemotherapy Alone in Routine Clinical Practice...
Trial ID:
Source:
Title:
Study of Bevacizumab Alone or Combined With Capecitabine and Oxaliplatin as Support Therapy in Metastatic Colorectal Cancer Patients
Excerpt:
...Overall survival`Overall response rate`Time to onset of response`Duration of response`Treatment cycles number`Number of patients who need medicine dose reduction`adverse events`Prognostic and predictive factor of Circulating endothelial cells (CEC) and circulating tumors cells (CTC) baseline and after 3 cycle`Prognostic factor of the K-Ras gene mutation...
Trial ID:
Source:
Title:
Study of Vitamin D in Untreated Metastatic Colorectal Cancer
Excerpt:
...- KRAS wild-type and KRAS mutant patients are eligible...
Trial ID:
Source:
Title:
Study Comparing Pathological Responses Observed on Colorectal Cancer Metastases Resected After Preoperative Bevacizumab With FOLFOX or FOLFIRI.
Excerpt:
...Wild-type or mutated KRAS tumor status....
Trial ID:
Source:
Title:
Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
Excerpt:
...Examine the influence of a potential predictive and prognostic tumour biomarker -mutations in K-RAS- after start of therapy on overall objective response`Examine the influence of a potential predictive and prognostic tumour biomarker -mutations in K-RAS- after start of therapy on surgical resection rate`Examine the influence of a potential predictive and prognostic tumour biomarker -mutations in K-RAS- after start of therapy on survival`Examine the influence of a potential predictive and prognostic tumour biomarker -mutations in K-RAS- after start of therapy on progression free survival...
Trial ID:
Source:
Title:
A Study of Avastin (Bevacizumab) in Combination With mFOLFOX6 in Treatment-Naïve Patients With Metastatic Colorectal Cancer With or Without K-RAS Mutations, and Comparison to Cetuximab
Excerpt:
...Progression-free survival: native versus mutated K-RAS; tumour assessments according to RECIST criteria...
Trial ID:
Less C2 evidence
Source:
Title:
Safety and efficacy of trifluridine/tipiracil plus bevacizumab in RAS mutated patients with metastatic colorectal cancer
Published date:
05/25/2023
Excerpt:
Forty-two patients were enrolled. Median age was 67 years (range 41–79 years), 44% were male, 100% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1, 85% were KRAS and 15% NRAS mutant...DCR was 57.1% (90% CI, 44.6 %-69.3%, P = 0.0690), respectively. The median progression-free survival (PFS) was 4.6 months...FTD/TPI is an important therapeutic resource in refractory RAS mutated metastatic colorectal cancer that combines manageability and safety.
Secondary therapy:
trifluridine/tipiracil
DOI:
10.1200/JCO.2023.41.16_suppl.e15605
Source:
Title:
Dynamic changes in RAS gene status in circulating tumour DNA: a phase II trial of first-line FOLFOXIRI plus bevacizumab for RAS-mutant metastatic colorectal cancer (JACCRO CC-11)
Published date:
06/07/2022
Excerpt:
Therefore, this study aimed to carry out a biomarker analysis by liquid biopsy using updated data of the phase II trial of FOLFOXIRI plus bevacizumab as first-line chemotherapy for RAS-mutant mCRC. The levels of circulating tumour DNA (ctDNA) and specific KRAS and NRAS variants were evaluated using real-time PCR assays. ORR was 75.8% (95% confidence interval 65.1% to 86.5%). The median progression-free survival was 12.1 months, and the median overall survival (OS) was 30.2 months. Survival analysis indicated that the median OS from progression was significantly longer in patients with RAS mutation clearance than in those with RAS mutation in the ctDNA at disease progression (15.1 versus 7.3 months, hazard ratio: 0.21, P = 0.0046).
Secondary therapy:
FOLFOXIRI
DOI:
10.1016/j.esmoop.2022.100512
Source:
Title:
Efficacy and safety analysis of bevacizumab combined with capecitabine in the maintenance treatment of RAS-mutant metastatic colorectal cancer
Published date:
02/25/2022
Excerpt:
We aimed to investigate the differences in efficacy and safety between bevacizumab combined with capecitabine maintenance therapy and capecitabine monotherapy for RAS-mutant mCRC（as defined by mutations in KRAS and NRAS exons 2-4）controlled by bevacizumab plus FOLFIRI chemotherapy for at least 12 weeks. All patients were first treated with bevacizumab combined with FOLFIRI for at least 12 weeks of induction therapy. 78 patients were in the observation group (bevacizumab plus capecitabine) and 76 patients were in the control group (capecitabine alone). The median progression-free survival (mPFS)of patients was 9.0 months (95% CI 8.0-10.0) in the observation group and 7.2 months (95% CI 6.0-8.4) in the control group, with a statistically significant difference (p < 0.05). Bevacizumab combined with capecitabine was well tolerated and contributed to a longer PFS time than capecitabine alone...
Secondary therapy:
FOLFIRI + capecitabine
DOI:
10.1111/jcpt.13576
Source:
Title:
A multicenter phase II trial evaluating the efficacy of bevacizumab plus mFOLFOX6 for R0 surgical resection in advanced colorectal liver metastases harboring mutant-type KRAS: NEXTO-mt trial
Published date:
02/09/2022
Excerpt:
This multicenter phase II trial aimed to examine the efficacy and safety of bevacizumab plus mFOLFOX6 for advanced CRLMs harboring mutant-type KRAS….The rates of complete and partial responses were 0% and 62.1%, respectively….During the median follow-up of 30.7 months, the 3-year OS rate for all the patients was 64.4% with the median survival of 49.1 months....For advanced CRLMs harboring mutant-type KRAS, bevacizumab plus mFOLFOX6 achieved a high R0 resection rate, leading to favorable survival.
Secondary therapy:
Modified FOLFOX6
DOI:
10.1016/j.hpb.2022.02.001
Source:
Title:
Metastatic colorectal cancer in both sides of Aegean Sea: practice patterns and outcome
Published date:
02/03/2022
Excerpt:
RAS and BRAF mutation rates were found to be 36% and 39%, respectively. As first-line therapy, 196 (54%) patients received bevacizumab and Anti-EGFR treatments in combination with chemotherapy….Objective response rate was 42% (n = 152) and 32% (n = 78) for 1st line and 2nd line treatments, respectively. While the median progression free survival (PFS) with the 1st line treatment was 10 months, it was 7 months with the 2nd line treatments. In the total study population median PFS and overall survival (OS) were 10 (95% CI, 8.3 - 11.6) and 35 (95% CI, 30.7 - 39.2) months, respectively.... it was found that wild RAS and BRAF mutations and second metastasectomy contributed to overall survival (p = 0.047 and p < 0.001).
Secondary therapy:
Chemotherapy + THE-349
DOI:
https://doi.org/10.1080/03007995.2022.2037848
Source:
Title:
A multicenter phase II trial to assess the efficacy and safety of bevacizumab plus mFOLFOX6 as induction chemotherapy toward R0 surgical resection in advanced colorectal liver metastases with mutant-type KRAS: NEXTO-mt trial
Published date:
01/18/2022
Excerpt:
Patients who had advanced CRLMs (tumor number of ≥5 and/or technically unresectable) harboring mutant-type KRAS were included in this study. The induction chemotherapy of bevacizumab plus mFOLFOX6 was administered and assessed for resectability every 4 cycles. The rates of complete and partial responses were 0% and 62.1%, respectively. R0 and R1 resections were performed in 19 and 1 patient, respectively (R0 resection rate: 65.5%). The 3-year PFS and OS rates were 7.4%, and 64.4%, respectively. The 3-year RFS rate was 10.0% in 20 patients who achieved R0 or R1 resections. Bevacizumab plus mFOLFOX6 achieved a high R0 resection rate with a favorable survival for patients with advanced CRLMs harboring mutant-type KRAS.
Secondary therapy:
Modified FOLFOX6
DOI:
10.1200/JCO.2022.40.4_suppl.450
Source:
Title:
Chemotherapy (doublet or triplet) plus targeted therapy by RAS status as conversion therapy in colorectal cancer patients with initially unresectable liver-only metastases. The UNICANCER PRODIGE-14 randomised clinical trial
Published date:
01/06/2022
Excerpt:
PRODIGE 14 was an open-label, multicenter, randomised Phase 2 trial. CRC patients with initially defined unresectable liver-only metastases received either, 2-CTx (FOLFOX or FOLFIRI) or 3-CTx (FOLFIRINOX), plus bevacizumab/cetuximab by RAS status. We failed to increase from 50 to 70% the R0/R1 liver-resection rate with the use of 3-CTx combined with bevacizumab or cetuximab by RAS status in CRC patients with initially unresectable liver metastases.
Secondary therapy:
FOLFIRINOX
DOI:
10.1038/s41416-021-01644-y
Source:
Title:
Bevacizumab Plus mFOLFOX6 Versus mFOLFOX6 Alone as First-Line Treatment for RAS Mutant Unresectable Colorectal Liver-Limited Metastases: The BECOME Randomized Controlled Trial
Published date:
08/04/2020
Excerpt:
For patients with initially unresectable RAS mutant colorectal liver metastases, bevacizumab combined with mFOLFOX6 increased the resectability of liver metastases and improved response rates and survival compared with mFOLFOX6 alone.
Secondary therapy:
Modified FOLFOX6
DOI:
10.1200/JCO.20.00174
Source:
Title:
Phase II randomised study of maintenance treatment with bevacizumab or bevacizumab plus metronomic chemotherapy after first-line induction with FOLFOXIRI plus Bevacizumab for metastatic colorectal cancer patients: the MOMA trial
Excerpt:
Between May 2012 and March 2015, 232 patients, mostly with RAS (65%) or BRAF (9%) mutant tumours, were randomised in 16 Italian centres....The activity of FOLFOXIRI plus bevacizumab is confirmed in a population with high prevalence of RAS/BRAF mutations treated with a 4-months induction.
Secondary therapy:
FOLFOXIRI
DOI:
10.1016/j.ejca.2018.12.028
Trial ID:
Source:
Title:
KRAS as prognostic biomarker in metastatic colorectal cancer patients treated with bevacizumab: a pooled analysis of 12 published trials
Excerpt:
CONTRADICTING EVIDENCE: Median PFS was significantly longer in KRAS wt patients compared with that in KRAS mut patients (HR = 0.85; 95 % confidence interval (CI) 0.74-0.98; P = 0.02). Similarly, median OS was significantly better in wt KRAS patients compared with that in mut KRAS patients (HR = 0.65; 95 % CI 0.46-0.92; P = 0.01).
