| General information |
| Database: | DB00821 |
| Objective: | Epidermal growth factor receptor (EGFR) mutations have been associated with tumor response to treatment with singleagent EGFR inhibitors in patients with relapsed non small cell lung cancer (non small cell lung cancer). The implications of EGFR mutations in patients treated with EGFR inhibitors plus firstline chemotherapy are unknown. KRAS is frequently activated in non small cell lung cancer. The relationship of KRAS mutations to outcome after EGFR inhibitor treatment has not been described. |
| Authors: | Eberhard DA, et al |
| Title: | 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. |
| Journal: | J Clin Oncol. |
| Year: | 2005 |
| PMID: | 16043828 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | chemotherapy + erlotinib |
| Study Type: | phase III TRIBUTE study |
| Key Patients Feature: | Previously untreated patients with advanced non small cell lung cancer in the phase III TRIBUTE study |
| Biomarker: | 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. |
| Biomark Analysis: | KRAS mutations (21% of tumors) were associated with significantly decreased TTP and survival in erlotinib plus chemotherapytreated patients. |
| Control Group Info: | chemotherapy alone verus and chemotherapy in combination with erlotinib |
| Treatment Info: | patients were randomly assigned to carboplatin and paclitaxel with erlotinib or placebo and were assessed for survival, response, and time to progression (TTP). |
| Primary End Point: | biomarker analyses |
| Secondary End Point: | NA |
| Patients Number: | 274 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Improved ORR to treatment with erlotinib plus CP was observed among patients with EGFRmutant tumors (53%) versus patients with wildtype tumors (18%; P < .01). In patients with KRASmutant tumors, ORR was 8% for those receiving erlotinib plus CP, compared with 23% in the subgroup receiving CP alone (P = .16; 95% CI for difference, 5% to 35%). |
| Disease Control Rate: | NA |
| Median Time to Progression: | 4.8 months for patients without sequence versus 5.4 months for patients with sequence (P = .12). |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 10.2 months (without sequence) versus 11.5 months (with sequence; P = .38) |
| Adverse Event(agent arm): | NA |
| Conclusions: | EGFR mutations may be a positive prognostic factor for survival in advanced non small cell lung cancer patients treated with chemotherapy with or without erlotinib, and may predict greater likelihood of response. Patients with KRASmutant non small cell lung cancer showed poorer clinical outcomes when treated with erlotinib and chemotherapy. Further studies are needed to confirm the findings of this retrospective subset analysis |