| General information |
| Database: | DB00780 |
| Objective: | cMET (MET) receptor activation is associated with poor prognosis and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non small cell lung cancer (non small cell lung cancer). This global, randomizedphase II trial examined erlotinib plus tivantinib (ARQ 197; ArQule, Woburn, MA), a novel MET inhibitor. |
| Authors: | Sequist LV, et al |
| Title: | Randomizedphase II study of erlotinib plus tivantinib versus erlotinib plus placebo in previously treated non small cell lung cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2011 |
| PMID: | 21768463 |
| Trial Design |
| Clinical Trial Id: | NCT00777309 |
| 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: | 1 |
| Therapeutic Combination Content: | erlotinib + tivantinib |
| Study Type: | Randomizedphase II study |
| Key Patients Feature: | Previously treated patients with EGFR TKInaive advanced non small cell lung cancer |
| Biomarker: | EGFR mutation and MET gene copy number |
| Biomark Analysis: | Objective responses were seen in 10% of patients on ET, 7% of patients on EP, and in two patients who crossed over from EP to ET, including one with EGFR mutation and MET gene copy number greater than 5. |
| Control Group Info: | erlotinib plus tivantinib versus erlotinib plus placebo |
| Treatment Info: | patients were randomly assigned to receive oral erlotinib (150 mg daily) plus oral tivantinib (360 mg twice daily) or erlotinib plus placebo (EP). At the time of progression, crossover from EP to erlotinib plus tivantinib (ET) was permitted. Archival tumor tissue specimens were required. |
| Primary End Point: | progression free survival (PFS). |
| Secondary End Point: | NA |
| Patients Number: | 167 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 10% in the ET arm and 7% in the EP arm |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.8 months for ET and 2.3 months for EP (hazard ratio [HR], 0.81; 95% CI, 0.57 to 1.16; P = .24). |
| Median OS A vs. C: | 8.5 months for ET and 6.9 months for EP (HR, 0.87; 95% CI, 0.59 to 1.27; P = .47) |
| Adverse Event(agent arm): | Fatigue, anorexia, nausea, vomiting, and dyspnea were also common. There was no significant increase in the rates of overall or serious adverse events on ET compared with EP, including neutropenia (Table 3). Thirtyeight patients died within 30 days of treatment (21 on EP, 17 on ET). |
| Conclusions: | The combination of the MET inhibitor tivantinib and erlotinib is welltolerated. Although the study did not meet its primary end point, evidence of activity was demonstrated, especially among patients with KRAS mutations. Additional study of tivantinib and erlotinib in patients with non small cell lung cancer is planned. |