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Association details:
| Biomarker: | KRAS mutation |
|---|---|
| Cancer: | Non Small Cell Lung Cancer |
| Drug: | erlotinib (EGFR inhibitor) |
| Direction: | Resistant |
Evidence:
Source:
Title:
Phosphoinositide-3-Kinase Catalytic Alpha and KRAS Mutations are Important Predictors of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Advanced Non-small Cell Lung Cancer
Excerpt:
...we have investigated PIK3CA, EGFR, and KRAS gene mutations in patients with advanced NSCLC who had been treated with gefitinib or erlotinib...Median TTP was significantly shorter in the patients with mutated PIK3CA and KRAS (log-rank test, p=0.01, and p=0.003...PIK3CA and KRAS mutations seem to be indicators of resistance and poor survival in patients with NSCLC treated with EGFR-TKIs.
DOI:
https://doi.org/10.1097/JTO.0b013e31820a3a6b
Source:
Title:
Value of KRAS as prognostic or predictive marker in NSCLC: results from the TAILOR trial
Excerpt:
In the mutated KRAS population, 2/20 patients (10%) experienced objective response to docetaxel and none to erlotinib (N = 24). In the wild-type population, 13/76 patients (17.1%) achieved objective response with docetaxel compared with 3/76 (3.9%) with erlotinib....Our analysis also failed to recognize KRAS as significant negative predictor for erlotinib efficacy...In the meanwhile, and with a pragmatic intent, our results confirm the superiority of docetaxel over erlotinib independently from KRAS, essentially showing an even more favorable trend precisely in the double wild-type subgroup (EGFR and KRAS wild-type).
DOI:
10.1093/annonc/mdv318
Trial ID:
Source:
Title:
Randomized, Double-Blind Trial of Erlotinib/Pazopanib or Erlotinib/Placebo in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer
Excerpt:
......
Trial ID:
Source:
Title:
Study of Polyphenon E in Addition to Erlotinib in Advanced Non Small Cell Lung Cancer
Excerpt:
...Phase 2: Correlation of KRAS mutations (in exons 2 and 3) in the original tumor tissue with treatment response and outcome....
Trial ID:
More C2 evidence
Source:
Title:
PF-00299804 As A Single Agent, In Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed Chemotherapy And Erlotinib
Excerpt:
...Best Overall Response (BOR) in Participants With Non-Adenocarcinoma Histology`Duration of Response (DR)`Percent Probability of Progression-free Survival (PFS) at Month 6`Percent Probability of Overall Survival at Months 6 and 12`Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)]`Maximum Observed Plasma Concentration (Cmax)`Time to Reach Maximum Observed Plasma Concentration (Tmax)`Human Epidermal Growth Factor-2 (HER-2) and Epidermal Growth Factor Receptor (EGFR) Levels in Serum`Number of Participants With Human Epidermal Growth Factor Family (HER-Family) and Kirsten Rat Sarcoma (KRAS) Gene Mutation Status From Free Tumor Deoxy- Ribonucleic Acid (DNA) in Blood at Screening`European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score`European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Lung Cancer-13 (QLQ- LC13) Score`Dermatology Life Quality Index (DLQI) Score`Percentage of Participants With Progression-free Survival (PFS)...
Trial ID:
Source:
Title:
Erlotinib Therapy and Subsequent Development of Mechanisms of Secondary Resistance in Patients With NSCLC
Excerpt:
...Participants were classified into 4 potential resistant mechanism groups (4 genetic/ 1 histologic) based on evaluation of rebiopsy tissue: EGFR mutations (T790M mutation, exon 20 insertion), KRAS mutations, MET amplification or small-cell lung cancer (SCLC) transform using established methods.`...
Trial ID:
Source:
Title:
A Study of Erlotinib (Tarceva) in Participants With Non-Small Cell Lung Cancer (NSCLC)
Excerpt:
...Number of participants with KRAS gene mutation and who achieved clinical benefit status was reported. ...
Trial ID:
Source:
Title:
Erlotinib Hydrochloride and Cabozantinib-s-Malate Alone or in Combination as Second or Third Line Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer
Excerpt:
...- EGFR mutation status is unknown but tumor is positive for at least one alternative driver mutation, i.e: Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, v-raf murine sarcoma viral oncogene homolog B (BRAF) mutation, human epidermal growth factor receptor 2 (HER2) mutation, ret proto-oncogene (RET) rearrangement/fusion, or one...
Trial ID:
Source:
Title:
Tivantinib Plus Erlotinib Versus Placebo Plus Erlotinib for the Treatment of Non-squamous, Non-small-cell Lung Cancer
Excerpt:
...EGFR and KRAS mutation status prior to randomization, and MET status post randomization...
Trial ID:
Less C2 evidence
Source:
Title:
Impact of Systematic EGFR and KRAS Mutation Evaluation on Progression-Free Survival and Overall Survival in Patients with Advanced Non–Small-Cell Lung Cancer Treated by Erlotinib in a French Prospective Cohort (ERMETIC Project—Part 2)
Excerpt:
EGFR and KRAS mutations were significantly associated with PFS (HR = 0.5, CI 0.3-0.7 and HR = 1.2, CI 0.8-1.8, respectively, versus no mutation; LR p = 0.001). In the OS model, adjusted HR was 0.7 (0.4-1.0) for EGFR mutation and 1.7 (1.1-2.4) for KRAS (LR p = 0.004).
DOI:
https://doi.org/10.1097/JTO.0b013e318265b2b5
Source:
Title:
Non–Small-Cell Lung Cancer and Ba/F3 Transformed Cells Harboring the ERBB2 G776insV_G/C Mutation Are Sensitive to the Dual-Specific Epidermal Growth Factor Receptor and ERBB2 Inhibitor HKI-272
Excerpt:
As expected, A549 cells, expressing wild-type EGFR and mutant K-RAS, were resistant to both erlotinib and HKI-272 (IC50 >1 μmol/L),…
DOI:
10.1158/0008-5472.CAN-06-0971
