Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib
Phase 2 or 3 results paper on KRAS in Non-small-cell lung cancer, in Journal of Clinical Oncology (2005), one of the most cited Europe PMC records with KRAS in its title.
Overview
Purpose: Epidermal growth factor receptor (EGFR) mutations have been associated with tumor response to treatment with single-agent EGFR inhibitors in patients with relapsed non-small-cell lung cancer (NSCLC). The implications of EGFR mutations in patients treated with EGFR inhibitors plus first-line chemotherapy are unknown. KRAS is frequently activated in NSCLC. The relationship of KRAS mutations to outcome after EGFR inhibitor treatment has not been described.
Patients and methods: Previously untreated patients with advanced NSCLC in the phase III TRIBUTE study who were randomly assigned to carboplatin and paclitaxel with erlotinib or placebo were assessed for survival, response, and time to progression (TTP). EGFR exons 18 through 21 and KRAS exon 2 were sequenced in tumors from 274 patients. Outcomes were correlated with EGFR and KRAS mutations in retrospective subset analyses.
Results: EGFR mutations were detected in 13% of tumors and were associated with longer survival, irrespective of treatment (P <.001). Among erlotinib-treated patients, EGFR mutations were associated with improved response rate (P <.05) and there was a trend toward an erlotinib benefit on TTP (P =.092), but not improved survival (P =.96). KRAS mutations (21% of tumors) were associated with significantly decreased TTP and survival in erlotinib plus chemotherapy-treated patients.
Conclusion: EGFR mutations may be a positive prognostic factor for survival in advanced NSCLC patients treated with chemotherapy with or without erlotinib, and may predict greater likelihood of response. Patients with KRAS-mutant NSCLC showed poorer clinical outcomes when treated with erlotinib and chemotherapy. Further studies are needed to confirm the findings of this retrospective subset analysis.
Indexed on Europe PMC as PubMed record 16043828 (DOI 10.1200/jco.2005.02.857). Its title names KRAS and its text names Non-small-cell lung cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Clinical Trial, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea "Turn a brake back on: drugs that reactivate the PP2A phosphatase" and no figure has been checked by an editor.
One of the most cited trial reports Europe PMC returns for KRAS in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
- Matched by KRAS in the title and Non-small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.
- Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper.