ALK Inhibitor MK-2206 Versus Everolimus in Refractory Renal Cell Carcinoma
In vascular endothelial growth factor (VEGF)-refractory patients with renal cell cancer, MK-2206 (an allosteric inhibitor of ALK) did not demonstrate superiority to everolimus, according to research published by Eric Jonasch, MD, of MD Anderson Cancer Center, and colleagues, in the Annals of Oncology.
In this phase II study, 43 patients were randomized in a 2:1 distribution: 29 patients were treated with MK-2206 and 14 were treated with everolimus.
The trial was closed at the first futility analysis, with an observed progression-free survival of 3.68 months in the MK-2206 arm and 5.98 months in the everolimus arm. One complete response and three partial responses were observed in the MK-2206 arm, versus none in the everolimus arm. Due to rash and itching, dose reduction occurred in 37.9% of the MK-2206 group and in 21.4% of everolimus-treated patients.
Additionally, genomic analysis revealed that 57.1% of the patients in the group with progressive disease had either harmful TP53 mutations or ATM mutations or deletions, but none of the patients without progressive disease had TP53 or ATM defects. The investigators concluded that mutations in DNA-repair genes were associated with early disease progression.