Dr. Robert on the Trametinib METRIC Trial Results

Caroline Robert, MD, PhD
Published: Monday, Jun 04, 2012

Caroline Robert, MD, PhD, Head of Dermatology at the Institute Gustave Roussy in Paris, France, discusses results from the METRIC trial, which examined the oral targeted therapy trametinib, a first-in-class MEK inhibitor for patients with advanced melanoma.

The METRIC trial enrolled patients with advanced BRAF-mutated melanoma who had received up to one prior chemotherapy regimen. These patients were selected because MEK, which trametinib inhibits, is downstream from BRAF in the MAP kinase pathway.

In the trial, patients were randomized 2:1 to receive either trametinib or the standard chemotherapy for metastatic melanoma (dacarbazine or paclitaxel). The progression-free survival (PFS) for those taking trametinib was 4.8 months compared to 1.5 months for those receiving chemotherapy, which represented a 55% reduction in the risk of progression. Additionally, the response rate to trametinib was 22% compared to only 8% for those receiving chemotherapy.

Robert notes that the METRIC trial was design to allow crossover from the trametinib arm to the chemotherapy arm, following progression. This generally confounds the collection of an overall survival benefit; however, at the six-month interim analysis 81% of patients on the trametinib group were still alive, compared to 67% for those receiving chemotherapy.

Overall, the METRIC trial shows that inhibiting the MEK protein, using trametinib, resulted in a significant increase in PFS, higher response rates, and an increase in overall survival, when compared to chemotherapy alone.

<<< View more from the 2012 ASCO Conference

Caroline Robert, MD, PhD, Head of Dermatology at the Institute Gustave Roussy in Paris, France, discusses results from the METRIC trial, which examined the oral targeted therapy trametinib, a first-in-class MEK inhibitor for patients with advanced melanoma.

The METRIC trial enrolled patients with advanced BRAF-mutated melanoma who had received up to one prior chemotherapy regimen. These patients were selected because MEK, which trametinib inhibits, is downstream from BRAF in the MAP kinase pathway.

In the trial, patients were randomized 2:1 to receive either trametinib or the standard chemotherapy for metastatic melanoma (dacarbazine or paclitaxel). The progression-free survival (PFS) for those taking trametinib was 4.8 months compared to 1.5 months for those receiving chemotherapy, which represented a 55% reduction in the risk of progression. Additionally, the response rate to trametinib was 22% compared to only 8% for those receiving chemotherapy.

Robert notes that the METRIC trial was design to allow crossover from the trametinib arm to the chemotherapy arm, following progression. This generally confounds the collection of an overall survival benefit; however, at the six-month interim analysis 81% of patients on the trametinib group were still alive, compared to 67% for those receiving chemotherapy.

Overall, the METRIC trial shows that inhibiting the MEK protein, using trametinib, resulted in a significant increase in PFS, higher response rates, and an increase in overall survival, when compared to chemotherapy alone.

<<< View more from the 2012 ASCO Conference


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